Faculty Profiles - TAKEMOTO Mami

Papers - TAKEMOTO Mami

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ATXN2遺伝子のCAGリピートをホモ接合性に有し同胞と臨床病型が異なりパーキンソニズムと痙性を呈した症例

小坂田陽介, 松岡千加, 中田有美, 佐々木諒, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 64 ( 10 ) 755 - 755 2024.10

当院における2家系のSCAR8の検討

柚木太淳, 松岡千加, 小坂田陽介, 中野由美子, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 64 ( 10 ) 751 - 751 2024.10

レカネマブ治療に伴うAPOE遺伝子型検査の実際

森原隆太, 小坂田陽介, 池上憲, 平祐貴, 石田将大, 樹下明典, 柚木太淳, 武本麻美, 野村恵美, 河野智仁, 松岡千加, 山下徹, 加藤芙美乃, 深野智華, 平沢晃, 石浦浩之

Dementia Japan 38 ( 4 ) 681 - 681 2024.10

髄液中抗MOG抗体を指標にIVIGによる維持療法を行った再発性MOGADの一例

池上憲, 佐々木諒, 石田将大, 樹下明典, 平祐貴, 小坂田陽介, 武本麻美, 森原隆太, 柚木太淳, 山下徹, 石浦浩之

神経免疫学 29 ( 1 ) 262 - 262 2024.10

Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia. International journal

Yusuke Fukui, Ryuta Morihara, Xinran Hu, Yumiko Nakano, Taijun Yunoki, Mami Takemoto, Koji Abe, Toru Yamashita

Scientific reports 14 ( 1 ) 20521 - 20521 2024.9

Language：English Publishing type：Research paper (scientific journal)

The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia.

DOI： 10.1038/s41598-024-71212-w

Protective effect of scallop-derived plasmalogen against vascular dysfunction, via the pSTAT3/PIM1/NFATc1 axis, in a novel mouse model of Alzheimer's disease with cerebral hypoperfusion. International journal

Yun Zhai, Ryuta Morihara, Tian Feng, Xinran Hu, Yusuke Fukui, Zhihong Bian, Yuting Bian, Haibo Yu, Hongming Sun, Mami Takemoto, Yumiko Nakano, Taijun Yunoki, Ying Tang, Hiroyuki Ishiura, Toru Yamashita

Brain research 1828 148790 - 148790 2024.4

Language：English Publishing type：Research paper (scientific journal)

A strong relationship between Alzheimer's disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD.

DOI： 10.1016/j.brainres.2024.148790

A Unique Case of Sarcoid-associated Myelopathy Accompanied by Lung Cancer.

Koh Tadokoro, Yumi Nakada, Ryo Sasaki, Yumiko Nakano, Taijun Yunoki, Kotaro Shin, Masataka Taoka, Kiichiro Ninomiya, Emi Nomura, Mami Takemoto, Ryuta Morihara, Toru Yamashita

Internal medicine (Tokyo, Japan) 62 ( 23 ) 3531 - 3535 2023.12

Language：English Publishing type：Research paper (scientific journal)

The differential diagnosis of myelopathy in patients with malignancies may be challenging, as a spinal biopsy is not always applicable. A 66-year-old woman who had shown transient double vision and nausea developed spasticity and impaired deep sensation in both feet. Magnetic resonance imaging showed abnormal gadolinium enhancement of the brainstem, spinal meninges, and nerve root. Cerebrospinal fluid (CSF) revealed mild pleocytosis and elevated protein and decreased glucose levels, although CSF cytology was normal. Lung carcinoma was simultaneously detected, and noncaseating granuloma was detected from the hilar and axillary lymph nodes, so she was diagnosed with sarcoid-associated myelopathy. Her symptoms were kept stable by intravenous methylprednisolone, oral prednisolone, and methotrexate. This is the first case of sarcoid-associated myelopathy accompanied by lung cancer, suggesting the importance of clinical course, repetitive CSF cytology, and a biopsy of the lymph nodes to distinguish sarcoid-associated myelopathy from meningeal metastasis in patients with malignancies.

DOI： 10.2169/internalmedicine.0943-22

視線計測計を用いた認知機能検査の有用性

田所功, 福井裕介, 野村恵美, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二, 山下徹

日本老年医学会雑誌 60 ( 4 ) 476 - 477 2023.10

神経疾患患者における遠隔診療のニーズ調査

佐々木諒, 田所功, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

臨床神経学 63 ( Suppl. ) S261 - S261 2023.9

Foix-Chavany-Marie症候群を呈した持続性部分てんかんの一例

佐々木諒, 柚木太淳, 中田有美, 松岡千加, 田所功, 中野由美子, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 63 ( 9 ) 620 - 620 2023.9

脊髄性筋萎縮症患者7名に対するリスジプラムの治療効果

山下徹, 柚木太淳, 中田有美, 松岡千加, 佐々木涼, 田所功, 中野由美子, 武本麻美, 森原隆太, 石浦浩之

臨床神経学 63 ( Suppl. ) S215 - S215 2023.9

エフガルチギモドへのスイッチを行った抗アセチルコリン受容体抗体・抗横紋筋抗体陽性の全身型重症筋無力症の一例

中野由美子, 佐々木諒, 中田有美, 松岡千加, 小坂田陽介, 田所功, 野村恵美, 柚木太淳, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 63 ( 9 ) 621 - 621 2023.9

Foix-Chavany-Marie症候群を呈した持続性部分てんかんの一例

佐々木諒, 柚木太淳, 中田有美, 松岡千加, 田所功, 中野由美子, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 63 ( 9 ) 620 - 620 2023.9

エフガルチギモドへのスイッチを行った抗アセチルコリン受容体抗体・抗横紋筋抗体陽性の全身型重症筋無力症の一例

中野由美子, 佐々木諒, 中田有美, 松岡千加, 小坂田陽介, 田所功, 野村恵美, 柚木太淳, 武本麻美, 森原隆太, 山下徹, 石浦浩之

臨床神経学 63 ( 9 ) 621 - 621 2023.9

脊髄性筋萎縮症患者7名に対するリスジプラムの治療効果

山下徹, 柚木太淳, 中田有美, 松岡千加, 佐々木涼, 田所功, 中野由美子, 武本麻美, 森原隆太, 石浦浩之

臨床神経学 63 ( Suppl. ) S215 - S215 2023.9

神経疾患患者における遠隔診療のニーズ調査

佐々木諒, 田所功, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

臨床神経学 63 ( Suppl. ) S261 - S261 2023.9

ADSSL1遺伝子変異を認め心不全を発症したが早期介入にて改善しえたネマリンミオパチーの一例

柚木太淳, 中野由美子, 野村恵美, 中田有美, 佐々木諒, 田所功, 武本麻美, 森原隆太, 山下徹, 斎藤良彦, 西野一三

臨床神経学 63 ( 5 ) 322 - 322 2023.5

ADSSL1遺伝子変異を認め心不全を発症したが早期介入にて改善しえたネマリンミオパチーの一例

柚木太淳, 中野由美子, 野村恵美, 中田有美, 佐々木諒, 田所功, 武本麻美, 森原隆太, 山下徹, 斎藤良彦, 西野一三

臨床神経学 63 ( 5 ) 322 - 322 2023.5

Neuroprotective effects of carnosine in a mice stroke model concerning oxidative stress and inflammatory response. International journal

Xinran Hu, Yusuke Fukui, Tian Feng, Zhihong Bian, Haibo Yu, Ryuta Morihara, Xiao Hu, Yuting Bian, Hongming Sun, Mami Takemoto, Yumiko Nakano, Taijun Yunoki, Koji Abe, Toru Yamashita

Journal of the neurological sciences 447 120608 - 120608 2023.4

Language：English Publishing type：Research paper (scientific journal)

Carnosine (β-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1β was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1β, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke.

DOI： 10.1016/j.jns.2023.120608

A young female case of asymptomatic immune-mediated necrotizing myopathy: a potential diagnostic option of antibody testing for rhabdomyolysis. International journal

Ryo Sasaki, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Eri Katsuyama, Ichizo Nishino, Toru Yamashita

Neuromuscular disorders : NMD 33 ( 2 ) 183 - 186 2023.2

Language：English

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy (IMNM) is a neuromuscular disorder that presents muscle weakness in proximal extremities and/or the trunk with an elevation of creatine kinase (CK). Young and asymptomatic anti-HMGCR IMNM patients are very rare and a treatment regimen has not been established. The present case, a 17-year-old woman without any muscular symptoms, only showed hyperCKemia that was detected by chance. After close examinations, including a muscle biopsy and antibody search, she was diagnosed as anti-HMGCR IMNM, and initial treatment with methotrexate and continuous intravenous immunoglobulin seemed to be effective. The present case is the unusually young asymptomatic case of anti-HMGCR IMNM. The diagnosis was successfully made, leading to the early introduction of a treatment. Given the course of this case, we believe that the preceding antibody testing is one of the diagnostic option for rhabdomyolysis.

DOI： 10.1016/j.nmd.2022.12.012

Human Cord Blood-Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model. International journal

Hongming Sun, Ryuta Morihara, Tian Feng, Zhihong Bian, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Ryo Sasaki, Yusuke Fukui, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Koji Abe, Toru Yamashita

Cell transplantation 32 9636897231193069 - 9636897231193069 2023

Language：English Publishing type：Research paper (scientific journal)

Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.

DOI： 10.1177/09636897231193069

Tocovid Attenuated Oxidative Stress and Cognitive Decline by Inhibiting Amyloid-β-Induced NOX2 Activation in Alzheimer's Disease Mice. International journal

Zhihong Bian, Haibo Yu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: NADPH oxidase 2 (NOX2) is an important source of reactive oxygen species (ROS). Activated NOX2 may contribute to Alzheimer's disease (AD). Our previous studies showed that a novel vitamin E mixture, Tocovid, had potential neuroprotective effects in a stroke mice model and an AD cell model. OBJECTIVE: The aim of this study was two-fold: to assess whether long-term Tocovid treatment can regulate NOX2, and the therapeutic effects of long-term administration of Tocovid to an AD mice model. METHODS: Therapeutic effects of long-term administration of Tocovid (200 mg/kg /day) on an Aβ-overexpressed transgenic AD mice model (APP23, n = 8) was investigated. The therapeutic effect of Tocovid in 16-month-old mice compared with the no-treatment APP23 group (n = 9) was assessed. RESULTS: Tocovid treatment strongly improved motor and memory deficits of APP23 mice by attenuating NOX2 expression, oxidative stress, neuroinflammation, neurovascular unit dysfunction, synaptic alteration, and Aβ deposition after 16 months. CONCLUSION: These findings suggest that NOX2 is a potential target in AD pathology. Long-term administration of Tocovid may be a promising candidate for AD treatment.

DOI： 10.3233/JAD-220761

Actual Telemedicine Needs of Japanese Patients with Neurological Disorders in the COVID-19 Pandemic.

Ryo Sasaki, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Koji Abe, Toru Yamashita

Internal medicine (Tokyo, Japan) 62 ( 3 ) 365 - 371 2022.11

Language：English Publishing type：Research paper (scientific journal)

Objective During the coronavirus disease 2019 (COVID-19) pandemic, many social activities have moved online using applications for digital devices (e.g. computers, smartphones). We investigated the needs of telemedicine and trends in medical status and social care situations of Japanese patients with neurological disorders in order to estimate their affinity for an online telemedicine application. Methods We designed an original questionnaire for the present study that asked participants what problems they had with hospital visits, how the COVID-19 pandemic had affected their lives, and whether or not they would like to receive telemedicine. Patients The present study included volunteer caregivers, participants with Parkinson's disease (PD), epilepsy, stroke, dementia, immune-mediated neurological disease (IMMD), spinocerebellar degeneration (SCD), amyotrophic lateral sclerosis (ALS), headache, myopathy, and other neurological diseases from Okayama University Hospital. Results A total of 29.6% of patients wanted to use telemedicine. Patients with headaches (60.0%) and epilepsy (38.1%) were more likely to want to use telemedicine than patients with PD (17.8%) or stroke (19.0%). Almost 90% of patients had access to a digital device, and there was no association between favoring telemedicine, ownership of a digital device, hospital visiting time, or waiting time at the hospital, although age was associated with motivation to telemedicine use (52.6 vs. 62.2 years old, p <0.001*). Conclusion We can contribute to the management of the COVID-19 pandemic and the medical economy by promoting telemedicine, especially for young patients with headaches or epilepsy.

DOI： 10.2169/internalmedicine.9702-22

Novel <scp> ABCD1 </scp> mutation detected in a symptomatic female carrier of adrenoleukodystrophy

Yumiko Nakano, Yuki Taira, Ryo Sasaki, Koh Tadokoro, Taijun Yunoki, Emi Nomura, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Nobuyuki Shimozawa, Toru Yamashita

Neurology and Clinical Neuroscience 2022.10

Anti-oxidative and the anti-inflammatory response of carnosine in a mice stroke model(和訳中)

胡欣冉, 阿部康二, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

脳循環代謝 34 ( 1 ) 153 - 153 2022.10

視線計測計を用いた認知機能障害の早期スクリーニング

福井裕介, 田所功, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 150 - 150 2022.10

Efficiency of Plasmalogen in a Mouse Model of Alzheimer's Disease with Cerebral Hypoperfusion(和訳中)

Zhai Yun, Feng Tian, 胡欣冉, 福井裕介, 卞之宏, Bian Yuting, 孫洪銘, 武本麻美, 柚木太淳, 中野由美子, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 160 - 160 2022.10

Rivaroxaban attenuated amyloid pathology and neuroinflammation by inhibiting PAR-1/PAR-2 in AD mice(和訳中)

Bian Zhihong, Liu Xia, Yu Haibo, Hu Xinran, Bian Yuting, Sun Hongming, 田所功, 武本麻美, 柚木太淳, 中野由美子, 福井裕介, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 158 - 158 2022.10

腺性自己免疫症候群3型に抗MOG抗体関連急性脊髄炎を合併した一例

柚木太淳, 中野由美子, 中田有美, 佐々木諒, 田所功, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

髄液検体から診断に至った再発性の抗MOG抗体関連疾患の2症例

中野由美子, 佐々木諒, 中田有美, 田所功, 柚木太淳, 野村恵美, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

腺性自己免疫症候群3型に抗MOG抗体関連急性脊髄炎を合併した一例

柚木太淳, 中野由美子, 中田有美, 佐々木諒, 田所功, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

視線計測計Gazefinderを用いた認知症診断の可能性

田所功, 福井裕介, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 小坂田陽介, 松本菜見子, 佐々木諒, 武本麻美, 菱川望, 森原隆太, 阿部康二, 山下徹

臨床神経学 62 ( Suppl. ) S323 - S323 2022.10

髄液検体から診断に至った再発性の抗MOG抗体関連疾患の2症例

中野由美子, 佐々木諒, 中田有美, 田所功, 柚木太淳, 野村恵美, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

視線計測計を用いた認知機能障害の早期スクリーニング

福井裕介, 田所功, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 150 - 150 2022.10

脳梗塞モデルマウスにおけるカルノシンの抗酸化作用と抗炎症作用(Anti-oxidative and the anti-inflammatory response of carnosine in a mice stroke model)

胡欣冉, 阿部康二, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

脳循環代謝 34 ( 1 ) 153 - 153 2022.10

RivaroxabanはADマウスのPAR-1/PAR-2阻害によりアミロイド病態と神経炎症を抑制する(Rivaroxaban attenuated amyloid pathology and neuroinflammation by inhibiting PAR-1/PAR-2 in AD mice)

Bian Zhihong, Liu Xia, Yu Haibo, Hu Xinran, Bian Yuting, Sun Hongming, 田所功, 武本麻美, 柚木太淳, 中野由美子, 福井裕介, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 158 - 158 2022.10

脳低灌流を伴うアルツハイマー病モデルマウスにおけるプラズマローゲンの有効性(Efficiency of Plasmalogen in a Mouse Model of Alzheimer's Disease with Cerebral Hypoperfusion)

Zhai Yun, Feng Tian, 胡欣冉, 福井裕介, 卞之宏, Bian Yuting, 孫洪銘, 武本麻美, 柚木太淳, 中野由美子, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 160 - 160 2022.10

Japanese case of Charcot-Marie-Tooth disease type 2Z with severe retinitis pigmentosa

Emi Nomura, Koh Tadokoro, Ryo Sasaki, Yumi Nakata, Yumiko Nakano, Taijun Yunoki, Mami Takemoto, Ryuta Morihara, Masahiro Ando, Hiroshi Takashima, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 10 ( 5 ) 266 - 268 2022.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Charcot-Marie-Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa.

DOI： 10.1111/ncn3.12660

A case of successful renal transplantation of Charcot-Marie-Tooth disease associated with FSGS due to mutation of the INF2 gene

Chika Matsuoka, Yuki Taira, Ryo Sasaki, Namiko Matsumoto, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Mami Takemoto, Ryuta Morihara, Akihiro Hashiguchi, Hiroshi Takashima, Hidemi Takeuchi, Motoo Araki, Koji Abe, Toru Yamashita

Neurology and Clinical Neuroscience 10 ( 5 ) 252 - 254 2022.9

Publishing type：Research paper (scientific journal)

Focal and segmental areas of glomerular sclerosis (FSGS) have various subcategories. Here, we report on a 35-year-old man who suffered from Charcot-Marie-Tooth disease (CMT) with FSGS carrying the INF2 mutation (c.206 T > C, p.L69P). The INF2 mutation might cause abnormal actin filaments of the podocytes and Schwann cells, leading to CMT associated with FSGS. He successfully underwent living donor kidney transplantation from a mother with a normal INF2 gene without any serious adverse events. Following genetic testing, the identification of the INF2 mutation allows a recipient to reduce the use of immunosuppressive drugs. Genetic testing may provide a treatment plan for kidney transplantation.

DOI： 10.1111/ncn3.12651

A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation

Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yumiko Nakano, Taijun Yunoki, Ryuta Morihara, Tatsuya Sasaki, Hiroyuki Akagawa, Koji Abe, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 2022.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection.

DOI： 10.1111/ncn3.12649

ADマウスとヒトAD脳における、Aβ沈着を伴ったフィブリノゲンペプチド鎖集積の加速(Acceleration of the accumulation of fibrinogen peptide chains with Aβ deposition in AD mice and human AD brains)

卞之宏, 山下徹, 于海波, 胡欣冉, 卞宇てい, 孫洪銘, 田所功, 武本麻美, 森原隆太, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 22回 221 - 221 2022.6

視線計測計を用いた認知症の早期発見

田所功, 福井裕介, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二, 山下徹

日本抗加齢医学会総会プログラム・抄録集 22回 208 - 208 2022.6

ホヤ由来プラズマローゲンの脳梗塞モデルマウスにおける高酸化ストレス・抗炎症作用の検討

福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 22回 224 - 224 2022.6

虚血性脳卒中モデルマウスにてホタテ由来プラズマローゲンは酸化ストレスと炎症を阻害する(Scallop-derived plasmalogen prevent oxidative stress and inflammation in a mouse model of ischemic stroke)

胡欣冉, 阿部康二, 田馮, 福井裕介, 田所功, 卞之宏, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

日本抗加齢医学会総会プログラム・抄録集 22回 252 - 252 2022.6

Clinical and Pathological Benefits of Scallop-Derived Plasmalogen in a Novel Mouse Model of Alzheimer's Disease with Chronic Cerebral Hypoperfusion. International journal

Tian Feng, Xinran Hu, Yusuke Fukui, Zhihong Bian, Yuting Bian, Hongming Sun, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 86 ( 4 ) 1973 - 1982 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer's disease (AD) patients. OBJECTIVE: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20-30% among the dementia society, were still elusive. METHODS: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. RESULTS: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-β pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. CONCLUSION: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.

DOI： 10.3233/JAD-215246

A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages

Emi Nomura, Yuko Kawahara, Yoshio Omote, Yoshiaki Takahashi, Namiko Matsumoto, Ken Ikegami, Mami Takemoto, Nozomi Hishikawa, Yumiko Nakano, Taijun Yunoki, Ryuta Morihara, Masahiro Uemura, Koji Abe, Toru Yamashita

Neurology and Clinical Neuroscience 10 ( 2 ) 98 - 101 2022.3

Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models. International journal

Ryuta Morihara, Toru Yamashita, Yosuke Osakada, Tian Feng, Xinran Hu, Yusuke Fukui, Koh Tadokoro, Mami Takemoto, Koji Abe

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 42 ( 7 ) 271678X221079127 - 1334 2022.2

Language：English Publishing type：Research paper (scientific journal)

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.

DOI： 10.1177/0271678X221079127

Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer's Disease Mice. International journal

Zhihong Bian, Xia Liu, Tian Feng, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 86 ( 1 ) 111 - 123 2022

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer's disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. OBJECTIVE: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. METHODS: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. RESULTS: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. CONCLUSION: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

DOI： 10.3233/JAD-215318

Aromatherapy for women migraine patients

Ueno Setsuko, Hishikawa Nozomi, Matsumoto Namiko, Hayashi Saori, Wakutani Yousuke, Tadokoro Koh, Takemoto Mami, Nomura Emi, Sasaki Ryo, Morihara Ryuta, Yamashita Toru, Takao Yoshiki

Japanese Journal of Headache 49 ( 1 ) 215 - 222 2022

Language：Japanese Publisher：The Japanese Headache Society

Chronic headache is a common neurological disease, which sometimes interfere business and life especially in women. In the present study, we newly created a headache diary for catching details of the patients’headache, and conducted an interventional open label cross-over study（each average 28 days）with or without aromatherapy using lavender（n＝12）or geranium（n＝12）．With these aromatic oil therapy, more than 80%of the headache patients（mean age 38.3±12.9 years old, 22 cases＝migraine, 2 cases＝migraine＋tension headache）felt relaxed. Aromatherapy reduced a 4.4%of drug intake on the headache day as compared to the non-aromatherapy period. Aromatherapy shortened the mean sleep-in time from 26.4 to 21.2min. Unfavorable effects on the daily business and house lives decreased in aromatherapy period than non-aroma period from 70.8 to 58.3%．These results suggest a positive effect of the aromatherapy for chronic headache women for giving relaxation and decreasing business stress, and making a short sleep-in．

DOI： 10.50860/jjho.49.1_215

Chronic Beneficial Effect of Makeup Therapy on Cognitive Function of Dementia and Facial Appearance Analyzed by Artificial Intelligence Software. International journal

Koh Tadokoro, Toru Yamashita, Junko Sato, Yoshio Omote, Mami Takemoto, Ryuta Morihara, Koichiro Nishiura, Tomiko Tani, Koji Abe

Journal of Alzheimer's disease : JAD 85 ( 3 ) 1189 - 1194 2021.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Makeup greatly impacts normal social lives but can also be a non-pharmacological form of therapy for dementia. OBJECTIVE: To evaluate the therapeutic effect of makeup therapy. METHODS: We carried out a prospective interventional study on female nursing home residents with dementia, focusing on the chronic therapeutic effect of makeup therapy. Thirty-four patients who received either only skin care (control group, n = 16) or skin care plus makeup therapy (makeup therapy group, n = 18) once every 2 weeks for 3 months were assessed. RESULTS: Three months of makeup therapy significantly improved the Mini-Mental State Examination (MMSE) score compared with control patients ( *p < 0.05). Artificial intelligence (AI) software revealed that the appearance of age decreased significantly in the makeup group compared with the control, especially among patients without depression ( *p < 0.05). Furthermore, a larger AI happiness score was significantly correlated with a greater improvement of ADL in the makeup therapy group (r = 0.43, *p < 0.05). CONCLUSION: Makeup therapy had a chronic beneficial effect on the cognitive function of female dementia patients, while the chronic effect of makeup therapy on facial appearance was successfully detected by the present AI software.

DOI： 10.3233/JAD-215385

脳梗塞モデルマウスにおけるホヤ由来プラズマローゲンの神経保護作用の検討

福井裕介, 馮田, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹, 阿部康二

脳循環代謝 33 ( 1 ) 114 - 114 2021.11

Three cases of GFAP astrocytopathy, one with bilateral ovarian teratoma

Yosuke Osakada, Yoshio Omote, Yuki Taira, Chika Matsuoka, Ken Ikegami, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Kota Sato, Yuka Terasawa, Nozomi Hishikawa, Ryuta Morihara, Mami Takemoto, Akio Kimura, Takayoshi Shimohata, Toru Yamashita, Koji Abe

Neurology and Clinical Neuroscience 10 ( 1 ) 30 - 34 2021.11

外傷と脳循環代謝 in vitro及びin vivo血栓モデルにおける温熱照射と超音波照射の有効性と安全性の検討

森原隆太, 馮田, 小坂田陽介, 山下徹, 胡欣冉, 福井祐介, 田所功, 武本麻美, 阿部康二

脳循環代謝 33 ( 1 ) 49 - 49 2021.11

ALS患者脊髄では低酸素ストレスの増加が起きている

山下徹, 畠山哲宗, 佐藤恒太, 福井裕介, 武本麻美, 太田康之, 西山佳宏, 河井信行, 田宮隆, 阿部康二

神経治療学 38 ( 6 ) S267 - S267 2021.10

幹細胞移植は脳梗塞後の異常蛋白処理機構を変化させる

田所功, 福井裕介, 山下徹, 劉夏, 角田慶一郎, 商敬偉, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二

神経治療学 38 ( 6 ) S322 - S322 2021.10

機械的血栓回収による直接的血管損傷とNVU破綻ラットモデルにおける検討

佐々木諒, 山下徹, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二

神経治療学 38 ( 6 ) S265 - S265 2021.10

Accelerated accumulation of fibrinogen peptide chains with Aβ deposition in Alzheimer's disease (AD) mice and human AD brains. International journal

Zhihong Bian, Toru Yamashita, Xiaowen Shi, Tian Feng, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Yoshio Omote, Ryuta Morihara, Koji Abe

Brain research 1767 147569 - 147569 2021.9

Language：English Publishing type：Research paper (scientific journal)

Alzheimer's disease (AD) is a common neurodegenerative disease that is characterized by the abnormal accumulation of intracellular and extracellular amyloid-β (Aβ) as well as disruption of the blood brain barrier (BBB). Fibrinogen plays an essential role in regulating thrombosis, wound healing, and other biological functions. In the present study, we investigated the relationship between three polypeptide chains α, β, and γ (FGA, FGB, and FGG) and Aβ deposition in the APP23 plus chronic cerebral hypoperfusion (CCH) mice model as well as the human AD brain. FGA, FGB, and FGG accumulated when Aβ was deposited in neural cells and cerebral vessels. This deposition was significantly higher in AD plus CCH mice models relative to wild-type brains, and in human AD brains compared to control brains. The present study demonstrates that FGA, FGB, and FGG are associated with AD progress, and can thus be potential targets for the diagnosis and therapy of AD.

DOI： 10.1016/j.brainres.2021.147569

Successful treatment of anti-GAD antibody-associated autoimmune cerebellar ataxia with combined immunotherapies

Yoshio Omote, Chika Matsuoka, Ryo Sasaki, Nozomi Hishikawa, Yuko Kawahara, Emi Nomura, Namiko Matsumoto, Yuki Taira, Mami Takemoto, Ryuta Morihara, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Anti-glutamic acid decarboxylase (GAD) antibody (Ab)-associated autoimmune cerebellar ataxia (CA) is a rare neurological disorder, and a standardized therapy has not been established. Here, we report on a 58 year-old man with type 1 diabetes mellitus, who developed progressive CA with high levels of serum and cerebrospinal fluid (CSF) anti-GAD-Ab. He was initially treated with intravenous high-dose methylprednisolone and intravenous immunoglobulin (IVIg), but his CA was gradually worsened. Additional combined immunotherapies with plasma exchange, intravenous cyclophosphamide, and rituximab finally stabilized the progressive CA and suppressed the CSF anti-GAD-Ab index. Our case suggests the effectiveness of combined immunotherapies against progressive CA and the usefulness of the CSF anti-GAD-Ab index as a therapeutic indicator.

DOI： 10.1111/ncn3.12541

アパシーの成因・治療を考えるアルツハイマー病患者の不安定な精神状態へのより良い処方薬について

武本麻美, 太田康之, 菱川望, 山下徹, 野村恵美, 角田慶一郎, 佐々木諒, 田所功, 松本菜見子, 表芳夫, 阿部康二

老年精神医学雑誌 32 ( 増刊I ) 179 - 179 2021.9

アルツハイマー病患者における主観的・客観的睡眠障害

田所功, 太田康之, 菱川望, 野村恵美, 涌谷陽介, 高尾芳樹, 表芳夫, 武本麻美, 山下徹, 阿部康二

臨床神経学 61 ( Suppl. ) S302 - S302 2021.9

アルツハイマー病患者の不安定な精神状態へのより良い処方薬についての研究

武本麻美, 太田康之, 山下徹, 野村恵美, 表芳夫, 田所功, 佐々木諒, 松本菜見子, 角田慶一郎, 阿部康二

臨床神経学 61 ( Suppl. ) S300 - S300 2021.9

Early detection of cognitive decline in mild cognitive impairment and Alzheimer's disease with a novel eye tracking test. International journal

Koh Tadokoro, Toru Yamashita, Yusuke Fukui, Emi Nomura, Yasuyuki Ohta, Setsuko Ueno, Saya Nishina, Keiichiro Tsunoda, Yosuke Wakutani, Yoshiki Takao, Takahiro Miyoshi, Yasuto Higashi, Yosuke Osakada, Ryo Sasaki, Namiko Matsumoto, Yuko Kawahara, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Ryuta Morihara, Koji Abe

Journal of the neurological sciences 427 117529 - 117529 2021.8

Language：English Publishing type：Research paper (scientific journal)

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0.01 vs NC) and AD (**p < 0.01 vs NC, ##p < 0.01 vs MCI), and correlated well with the mini-mental state examination (MMSE) score (r = 0.57, *p < 0.05). Furthermore, the eye tracking test, especially memory and deductive reasoning tasks, effectively discriminated NC, MCI and AD. The present novel eye tracking test clearly discriminated cognitive functions among NC, MCI, and AD subjects, thereby providing an advantage for the early detection of MCI and AD in screening.

DOI： 10.1016/j.jns.2021.117529

A case of rheumatoid meningoencephalitis induced by pembrolizumab

Chika Matsuoka, Yoshio Omote, Yuko Kawahara, Ryo Sasaki, Namiko Matsumoto, Ko Tadokoro, Yuki Taira, Mami Takemoto, Ryuta Morihara, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 2021.8

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Immune checkpoint inhibitors occasionally cause various side effects, but the occurrence of a severe immune-related adverse event (irAE) is rare in neurology. We report on a 56-year-old woman who suffered from rheumatoid arthritis and recurrent uterine cancer. After treatment with pembrolizumab, she showed visual disturbance followed by acute fever and consciousness disturbance with high-intensity lesions around the midbrain aqueduct and bilateral caudate heads on FLAIR images of a brain MRI. Her symptoms improved after steroid therapy. However, symptoms relapsed leading to an elevation of the anti-CCP antibody index. Pembrolizumab-induced rheumatoid meningoencephalitis was suspected, so additional steroid therapy was provided. This improved her symptoms, turning the anti-CCP antibody index negative. The present case is the first case of rheumatoid meningoencephalitis induced by pembrolizumab. The combination of MRI findings and elevated anti-CCP index seems useful for diagnosing rheumatoid meningoencephalitis.

DOI： 10.1111/ncn3.12540

Switching the Proteolytic System from the Ubiquitin-Proteasome System to Autophagy in the Spinal Cord of an Amyotrophic Lateral Sclerosis Mouse Model. International journal

Koh Tadokoro, Toru Yamashita, Jingwei Shang, Yasuyuki Ohta, Emi Nomura, Ryuta Morihara, Yoshio Omote, Mami Takemoto, Koji Abe

Neuroscience 466 47 - 57 2021.7

Language：English Publishing type：Research paper (scientific journal)

The degradation of damaged proteins takes place via two major proteolytic pathways: the ubiquitin-proteasome system (UPS) and autophagy. However, since it is unclear how these two proteolytic pathways contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), we investigated the switching mechanism from UPS to autophagy by pharmacologically modifying these pathways by treating the spinal cords of female ALS mouse model bearing G93A human SOD1 (G93A mice) with MG132 or 3-methyladenine (3MA). G93A mice exhibited a progressive increase in the amount of ubiquitin and p62 aggregates, BAG3 expression, and LC3-II/LC3-I ratio in both astroglia and motor neurons. Treatment with MG132 or 3MA significantly increased the clinical hanging wire score and exacerbated α-motor neuron loss at 18 weeks in G93A mice, and increased the amount of ubiquitin, p62 aggregates, and BAG3 expression. This study's results demonstrate that the molecular switch from UPS to autophagy occurred not only in motor neurons but also in astroglia at the end stage (18 weeks) when the autophagic flux was impaired in G93A mice. This finding suggests that the defense system was disrupted against aggregate-prone protein production in ALS.

DOI： 10.1016/j.neuroscience.2021.04.034

A Unique Case of Encephalopathy with an Elevated IgG-4 and Extremely High Interleukin-6 Level and Delayed Myelodysplastic Syndrome.

Namiko Matsumoto, Nozomi Hishikawa, Ken Ikegami, Kota Sato, Yoshio Omote, Mami Takemoto, Toru Yamashita, Kohei Taniguchi, Koji Abe

Internal medicine (Tokyo, Japan) 60 ( 13 ) 2125 - 2128 2021.7

Language：English Publishing type：Research paper (scientific journal)

We herein report a 75-year-old man who developed disturbed consciousness with polynuclear cell dominant pleocytosis and low glucose and extremely high interleukin (IL)-6 levels in his cerebrospinal fluid. The biopsy specimen from his right supraclavicular lymph node showed the infiltration of inflammatory cells positive for IgG, IgG4 and IL-6. Prednisolone and azathioprine administered under suspicion of IgG4-related disease (IgG4-RD) or multicentric Castleman's disease (MCD) successfully remitted the symptoms. However, he developed myelodysplastic syndrome (MDS) and died 18 months later. The extremely high IL-6 may have been related to the rare neurological manifestations and development of MDS in the present case.

DOI： 10.2169/internalmedicine.6098-20

The first case of chronic inflammatory demyelinating polyneuropathy after transsexualism and continuous testosterone administration

Yuki Taira, Yoshio Omote, Yuko Kawahara, Emi Nomura, Ryo Sasaki, Namiko Matsumoto, Chika Matsuoka, Mami Takemoto, Ryuta Morihara, Nozomi Hishikawa, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 4 ) 346 - 348 2021.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report on a 35-year-old man who had gender dysphoria following unilateral ovariectomy and then received continuous testosterone injection for nine years, inducing chronic inflammatory demyelinating polyneuropathy (CIDP). He developed recurrent muscle weakness and numbness in the extremities and displayed demyelinating neuropathy, detected by nerve conduction studies and a sural nerve biopsy. Repeated intravenous immunoglobulin (IVIg) therapy and the administration of oral prednisolone improved symptoms and inhibited their recurrence. A relatively high level of serum testosterone as a genetic female might have caused the neurotoxicity of the peripheral nerve, leading to CIDP.

DOI： 10.1111/ncn3.12514

AIを用いたパーキンソン病患者の見た目年齢・感情の評価

田所功, 山下徹, 福井裕介, 武本麻美, 佐々木諒, 松本菜見子, 野村恵美, 森原隆太, 表芳夫, 阿部康二

パーキンソン病・運動障害疾患コングレスプログラム・抄録集 15回 81 - 81 2021.7

Author Correction: Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis. International journal

Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe

Scientific reports 11 ( 1 ) 12828 - 12828 2021.6

Hypoxic stress visualized in the cervical spinal cord of ALS patients. International journal

Toru Yamashita, Tetsuhiro Hatakeyama, Kota Sato, Yusuke Fukui, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Yoshihiro Nishiyama, Nobuyuki Kawai, Takashi Tamiya, Koji Abe

Neurological research 43 ( 6 ) 429 - 433 2021.6

Language：English Publishing type：Research paper (scientific journal)

Objective: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Hypoxic stress is suspected as the pathogenesis of ALS, however, no positron emission tomography (PET) study for hypoxic stress has been conducted in the spinal cord of ALS patients.Methods: In the present study, we examined cervical spinal hypoxic stress of nineALS patients with upper extremity (U/E) atrophy by18F-fluoromisonidazole (FMISO) PET.Results: On the ipsilateral side of C1 and C5 levels, 18F-FMISO uptake increased significantly compared with the contralateral side (*p < 0.05) and the control subject (**p < 0.01). In addition, a strong correlation was found between 18F-FMISO uptake of the C5 level and the rate of progression of the ALS FRS-R score (R = 0.781, *p = 0.013).Conclusion: These results indicate that hypoxic stress increased in the spinal cord of ALS patients with a close link to ALS progression. Both hypoxic stress and a compromised response to hypoxia, which may lead to subsequent motor neuron death, could be a potential therapeutic target for ALS.

DOI： 10.1080/01616412.2020.1866383

ALS患者における低酸素ストレスを可視化する

山下徹, 畠山哲宗, 佐藤恒太, 福井裕介, 菱川望, 武本麻美, 太田康之, 西山佳宏, 河井信行, 田宮隆, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 21回 214 - 214 2021.6

化粧美容セラピーの認知・情動機能改善効果

田所功, 川野公子, 佐藤順子, 谷都美子, 表芳夫, 武本麻美, 森原隆太, 山下徹, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 21回 211 - 211 2021.6

AIを用いたパーキンソン病の顔についての解析

田所功, 山下徹, 福井裕介, 武本麻美, 佐々木諒, 松本菜見子, 野村恵美, 表芳夫, 森原隆太, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 21回 222 - 222 2021.6

AIによる新しい脳機能・認知症診断 AIなどの新たな技術を活用した認知症診療

田所功, 佐々木諒, 松本菜見子, 福井裕介, 表芳夫, 武本麻美, 森原隆太, 山下徹, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 21回 155 - 155 2021.6

ALS患者における低酸素ストレスを可視化する

山下徹, 畠山哲宗, 佐藤恒太, 福井裕介, 菱川望, 武本麻美, 太田康之, 西山佳宏, 河井信行, 田宮隆, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 21回 214 - 214 2021.6

Neuroprotective effect of CuATSM in mice stroke model by ameliorating oxidative stress. International journal

Xiaowen Shi, Yasuyuki Ohta, Yumiko Nakano, Xia Liu, Koh Tadokoro, Tian Feng, Emi Nomura, Keiichiro Tsunoda, Ryo Sasaki, Namiko Matsumoto, Yosuke Osakada, Yuting Bian, Zhihong Bian, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

Neuroscience research 166 55 - 61 2021.5

Language：English Publishing type：Research paper (scientific journal)

Cu-diacetyl-bis (N4-methylthiosemicarbazone) (CuATSM) has both anti-oxidative and anti-inflammatory activities, but its therapeutic efficacy for oxidative stress has not been thoroughly investigated in acute ischemic stroke. Here, the present study was designed to assess the efficacies of CuATSM in acute ischemic stroke by comparing with the standard neuroprotective reagent edaravone. Mice were subjected to transient middle cerebral occlusion (tMCAO) for 60 min, and then intravenously administrated with CuATSM (1.5 mg/kg) or edaravone (3 mg/kg) just after the reperfusion, and examined at 1 and 3 d. Compared with the vehicle group, CuATSM treatment decreased infarct volumes and oxidative stress at 3d after tMCAO, which was further enhanced by combined CuATSM + edaravone treatment as compared with single CuATSM group, but not improve neurobehaviors. The present study demonstrated that CuATSM showed strong antioxidative and neuroprotective effects in acute ischemic stroke, which was enhanced by the combination with edaravone.

DOI： 10.1016/j.neures.2020.05.009

Positive baseline behavioral and psychological symptoms of dementia predict a subsequent cognitive impairment in cognitively normal population

Keiichiro Tsunoda, Toru Yamashita, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Emi Nomura, Noriko Hatanaka, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 3 ) 218 - 222 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Background: Because behavioral and psychological symptoms of dementia (BPSD) are sometimes prodromal symptoms of dementia, it is important to investigate the relationship between BPSD and subsequent cognitive decline.Methods: We examined the cognitive and affective functions of 76 cognitively normal subjects at initial assessment (baseline) and 1-year follow-up. Cognitive function was assessed using clinical dementia rating (CDR) and Mini-Mental State Examination (MMSE), and affective function was assessed using Abe's BPSD score (ABS) and mild behavioral impairment (MBI).Results: Although there was no change in MMSE, ABS, or MBI after 1 year, the mean CDR score of 0 at baseline increased to 0.1 +/- 0.2 at 1-year follow-up (**P < 0.01 vs baseline). No significant change in MMSE was found in both baseline ABS and MBI positive- or negative-groups. In contrast, baseline MBI-dependent CDR change showed a 13.2% of worsening in MBI-negative subjects and a 62.5% of MBI-positive subjects (dagger dagger P < 0.01), but ABS not.Conclusion: The present data indicate that positive baseline BPSD with MBI was closely related to a subsequent CDR exacerbation. Examining BPSD may be useful for screening cognitively normal population for subsequent dementia development in local communities.

DOI： 10.1111/ncn3.12492

4-Hydroxyl-2-Nonenal Localized Expression Pattern in Retrieved Clots is Associated with Large Artery Atherosclerosis in Stroke Patients. International journal

Yosuke Osakada, Toru Yamashita, Ryuta Morihara, Namiko Matsumoto, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Yoshio Omote, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Yasuki Suruga, Takayuki Nagase, Yuji Takasugi, Satoshi Inoue, Kyoichi Watanabe, Kentaro Deguchi, Koji Tokunaga, Susumu Sasada, Kazuki Kobayashi, Ryosuke Maeoka, Kenji Fukutome, Kenkichi Takahashi, Hiroyuki Ohnishi, Yoshihiro Kuga, Hideyuki Ohnishi, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 30 ( 3 ) 105583 - 105583 2021.3

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: The relationship between stroke etiology and clot pathology remains controversial. MATERIALS AND METHODS: We performed histological analysis of clots retrieved from 52 acute ischemic stroke patients using hematoxylin and eosin staining and immunohistochemistry (CD42b and oxidative/hypoxic stress markers). The correlations between clot composition and the stroke etiological group (i.e., cardioembolic, cryptogenic, or large artery atherosclerosis) were assessed. RESULTS: Of the 52 clots analyzed, there were no significant differences in histopathologic composition (e.g., white blood cells, red blood cells, fibrin, and platelets) between the 3 etiological groups (P = .92). By contrast, all large artery atherosclerosis clots showed a localized pattern with the oxidative stress marker 4-hydroxyl-2-nonenal (P < .01). From all 52 clots, 4-hydroxyl-2-nonenal expression patterns were localized in 28.8% of clots, diffuse in 57.7% of clots, and no signal in 13.5% of clots. CONCLUSIONS: A localized pattern of 4-hydroxyl-2-nonenal staining may be a novel and effective marker for large artery atherosclerosis (sensitivity 100%, specificity 82%).

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105583

A new telestroke network system in northern area of Okayama prefecture

Ryo Sasaki, Toru Yamashita, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Taijun Yunoki, Kazuki Kobayashi, Takashi Sawata, Yuki Sato, Junichi Kubota, Masayuki Mizobuchi, Takashi Hayashi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 2 ) 166 - 170 2021.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Background: Telestroke network can provide rapid access to specialized treatment and improves on-site management of acute stroke patients through the "hub-and-spoke" model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID-19), it is required to reduce the unnecessary contact with stroke patients from other hospitals.Aim: We organized a novel cost-free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area.Method: We prepared the tablet device on which Skype(R) application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed.Results: During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice.Conclusion: The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID-19.

DOI： 10.1111/ncn3.12475

The Oldest Japanese Case of Combined Central and Peripheral Demyelination, which Developed Nine Years After the First Instance of Optic Neuritis.

Emi Nomura, Yuko Kawahara, Yoshio Omote, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Hidenori Ogata, Koji Abe

Internal medicine (Tokyo, Japan) 60 ( 2 ) 305 - 308 2021.1

Language：English Publishing type：Research paper (scientific journal)

Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive anti-neurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD.

DOI： 10.2169/internalmedicine.5536-20

A case of autoimmune GFAP astrocytopathy with profound weight loss and increased uptake in the spinal cord on F-18-FDG PET

Yosuke Osakada, Yoshio Omote, Ken Ikegami, Koh Tadokoro, Kota Sato, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Akio Kimura, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 1 ) 95 - 97 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

A 76-year-old man presented with subacute onset of progressive cognitive impairment, anorexia, tremor, ataxic gait, and urinary dysfunction. He had lost 17 kg in 9 months before his admission (due to persistent anorexia). A brain MRI showed a typical radial pattern of periventricular gadolinium enhancement and longitudinally extensive hyperintensity from cervical to lumbar spinal cord. F-18-FDG PET newly revealed an increased uptake of the tracer in the cervical and lower thoracic cords. After an intravenous methylprednisolone (1000 mg/d for 3 days) followed by oral prednisolone 40 mg/d, his clinical symptoms and abnormal MRI lesions improved. Anti-GFAP antibodies were subsequently identified in CSF obtained on admission, confirming the diagnosis of autoimmune GFAP astrocytopathy.

DOI： 10.1111/ncn3.12441

A case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex presenting as progressive parkinsonism with corresponding tau imaging

Yasuyuki Ohta, Hitoshi Shimada, Ken Ikegami, Keiichiro Tsunoda, Nozomi Hishikawa, Toru Yamashita, Mami Takemoto, Yoshio Omote, Kenji Tagai, Kiwamu Matsuoka, Makoto Higuchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 9 ( 1 ) 124 - 126 2021.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC), frequently observed in the Kii peninsula of Japan, is pathologically characterized by widespread tau pathology in the cerebrum and brainstem. Here, we report a case of Kii ALS/PDC predominantly presenting progressive parkinsonism. Tau positron emission tomography (PET) imaging with F-18-PM-PBB3 suggested tau deposition in the substantia nigra of the midbrain and subcortical areas, but not in the cerebral cortex, which was similar to progressive supranuclear palsy (PSP), suggesting that parkinsonism-predominant type of Kii ALS/PDC may have a similar area of tau deposition to PSP.

DOI： 10.1111/ncn3.12463

Retinal Amyloid Imaging for Screening Alzheimer's Disease. International journal

Koh Tadokoro, Toru Yamashita, Shuhei Kimura, Emi Nomura, Yasuyuki Ohta, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Ryuta Morihara, Yuki Morizane, Koji Abe

Journal of Alzheimer's disease : JAD 83 ( 2 ) 927 - 934 2021

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cost-effective and noninvasive methods for in vivo imaging of amyloid deposition are needed to screen Alzheimer's disease (AD). Although retinal amyloid is a possible diagnostic marker of AD, there are very few studies on in vivo retinal amyloid imaging. OBJECTIVE: To examine the usefulness of in vivo imaging of retinal amyloid in AD patients. METHODS: To examine amyloid deposition, 30 Japanese subjects (10 normal control (NC), 7 with mild cognitive impairment (MCI), and 13 with AD) underwent a complete ophthalmic examination, including fundus imaging by scanning laser ophthalmoscopy before and after oral curcumin intake. RESULTS: Retinal amyloid deposition was greater in AD than in NC subjects (*p < 0.05) while MCI showed a slight but insignificant increase of retinal amyloid deposition relative to NC subjects. Retinal amyloid deposition was correlated with whole gray matter atrophy (r = 0.51, *p < 0.05) but not with the cognitive score of the Mini-Mental State Examination, nor with medial temporal lobe atrophy. CONCLUSION: The present noninvasive in vivo detection of retinal amyloid deposition is useful for screening AD patients.

DOI： 10.3233/JAD-210327

Immediate Beneficial Effect of Makeup Therapy on Behavioral and Psychological Symptoms of Dementia and Facial Appearance Analyzed by Artificial Intelligence Software. International journal

Koh Tadokoro, Toru Yamashita, Satoko Kawano, Junko Sato, Yoshio Omote, Mami Takemoto, Ryuta Morihara, Koichiro Nishiura, Natsuki Sagawa, Tomiko Tani, Koji Abe

Journal of Alzheimer's disease : JAD 83 ( 1 ) 57 - 63 2021

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Possible benefits of makeup therapy, in terms of immediate and late effects on cognitive and affective functions, have not been fully proved for dementia patients. OBJECTIVE: To evaluate the immediate effect of makeup therapy on dementia patients. METHODS: Female nursing home residents with dementia received either only skin care treatment (control group, n = 17) or skin care plus makeup therapy treatment (makeup therapy group, n = 19). Cognitive, affective, and activity of daily living (ADL) scores were evaluated before and just after treatments. Apparent age and emotion were also evaluated with artificial intelligence (AI) software. RESULTS: Makeup therapy significantly improved Abe's behavioral and psychological symptoms of dementia (BPSD) score (ABS, *p < 0.05). AI software judged that makeup therapy significantly made the apparent age younger (*p < 0.05). In particular, patients with moderate ADL scores had a significantly higher happiness score in makeup therapy (*p < 0.05), with a modest correlation to the Mini-Mental State Examination (MMSE, r = 0.42, *p < 0.05). The severe baseline MMSE group reported a greater feeling of satisfaction following makeup therapy (*p < 0.05). CONCLUSION: The present makeup therapy is a promising non-pharmacological approach to immediately alleviate BPSD in female dementia patients, and the present AI software quickly and quantitatively evaluated the beneficial effects of makeup therapy on facial appearance.

DOI： 10.3233/JAD-210284

Cerebral Microbleeds in Patients with Parkinson's Disease and Dementia with Lewy Bodies: Comparison Using Magnetic Resonance Imaging and 99 mTc-ECD SPECT Subtraction Imaging. International journal

Mami Takemoto, Toru Yamashita, Yasuyuki Ohta, Koh Tadokoro, Yoshio Omote, Ryuta Morihara, Koji Abe

Journal of Alzheimer's disease : JAD 80 ( 1 ) 331 - 335 2021

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cerebral microbleeds (CMBs) in patients with Parkinson's disease (PD) or dementia with Lewy bodies (DLB) have not been adequately studied. OBJECTIVE: This study aims to find a difference in the total number, prevalence, and common locations of CMBs between PD and DLB and evaluate 99 mTc-ECD SPECT subtraction images of these two diseases. METHODS: We examined 112 patients with PD (53 males and 59 females; age: 77.4±3.6 years) and 28 age-matched patients with DLB (15 males and 13 females; age: 77.1±6.7 years) using brain magnetic resonance imaging (MRI) and 99 mTc-ECD SPECT subtraction imaging. RESULTS: The total number of CMBs was higher in patients with DLB (41.2%) than in those with PD (11.5%), and the prevalence was significantly higher in the former (0.7±1.1) than the latter (0.2±0.5, p < 0.05). The odds ratio was 5.4 (95% confidence interval [CI]: 1.7-17.4). Furthermore, CMBs were commonly located in the basal ganglia of patients with PD (6 out of 87 patients) but in the occipital lobe of patients with DLB (8 out of 17 patients). 99 mTc-ECD SPECT subtraction imaging indicated lower cerebral blood flow in the posterior cingulate gyrus among the patients with CMB-positive DLB than among those with CMB-positive PD; additionally, the cerebral blood flow was lower in the bilateral basal ganglia and midbrain among patients with CMB-positive DLB compared to those with CMB-negative DLB. CONCLUSION: A reduction in occipital glucose metabolism may be related to CMBs in the occipital lobe of patients with DLB.

DOI： 10.3233/JAD-201495

Tocilizumab-induced Leukoencephalopathy with a Reversible Clinical Course.

Ryo Sasaki, Nozomi Hishikawa, Emi Nomura, Yoshio Omote, Mami Takemoto, Toru Yamashita, Noriko Hatanaka, Yasuto Higashi, Koji Abe

Internal medicine (Tokyo, Japan) 59 ( 22 ) 2927 - 2930 2020.11

Language：English Publishing type：Research paper (scientific journal)

Tocilizumab (TCZ; Actemra/RoActemra) is an anti-interleukin (IL)-6 receptor antibody for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases and cytokine storms. The present case is a 63-year-old female well-controlled RA patient, who presented with a progressive cognitive impairment after 34 months of TCZ administration. Brain magnetic resonance imaging (MRI) showed leukencephalopathy with a lactic acid peak in magnetic resonance spectroscopy (MRS), a decreased blood flow in single photon emission computed tomography (SPECT), and a decreased accumulation in fluorodeoxyglucose positron emission tomography (FDG-PET). The discontinuation of TCZ improved her cognitive function and brain MRI findings at 3 months after drug cessation. The present case suggests that TCZ may sometimes cause leukoencephalopathy after long-term administration, and thus the early discontinuation of TCZ is recommended to achieve a good prognosis.

DOI： 10.2169/internalmedicine.5288-20

Repeat sizes of NOP56 gene in a Japanese Asidan (SCA36) family with clinical anticipation. International journal

Yasuyuki Ohta, Ken Ikegami, Kota Sato, Nozomi Hishikawa, Yoshio Omote, Mami Takemoto, Toru Yamashita, Koji Abe

Journal of the neurological sciences 418 117150 - 117150 2020.11

ALS患者脊髄における低酸素ストレスを可視化する

山下徹, 畠山哲宗, 佐藤恒太, 福井裕介, 菱川望, 武本麻美, 太田康之, 西山佳宏, 河井信行, 田宮隆, 阿部康二

脳循環代謝 32 ( 1 ) 102 - 102 2020.11

認知機能正常者ならびに軽度認知障害における認知症周辺症状の出現

角田慶一郎, 山下徹, 小坂田陽介, 佐々木諒, 田所功, 松本菜見子, 野村恵美, 森原隆太, 中野由美子, 高橋義秋, 幡中典子, 商敬偉, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

臨床神経学 60 ( Suppl. ) S445 - S445 2020.11

アルツハイマー病患者の臨床的進行予測因子についての検討

菱川望, 表芳夫, 武本麻美, 太田康之, 山下徹, 阿部康二

臨床神経学 60 ( Suppl. ) S424 - S424 2020.11

PDDとDLBの認知機能と情動機能、脳血流画像の比較検討

武本麻美, 田所功, 表芳夫, 菱川望, 太田康之, 山下徹, 阿部康二

臨床神経学 60 ( Suppl. ) S408 - S408 2020.11

幹細胞移植による虚血脳のタンパク分解分子機構への影響

田所功, 福井裕介, 山下徹, 劉夏, 角田慶一郎, 商敬偉, 表芳夫, 武本麻美, 菱川望, 太田康之, 阿部康二

脳循環代謝 32 ( 1 ) 124 - 124 2020.11

同種骨髄移植が有用であった大脳型に進展した副腎白質ジストロフィーの1例

表芳夫, 佐藤恒太, 浦田知宏, 藤井伸治, 下澤伸行, 山下徹, 武本麻美, 菱川望, 太田康之, 阿部康二

臨床神経学 60 ( Suppl. ) S416 - S416 2020.11

Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis. International journal

Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe

Scientific reports 10 ( 1 ) 17102 - 17102 2020.10

Language：English Publishing type：Research paper (scientific journal)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0 × 104 cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients.

DOI： 10.1038/s41598-020-74216-4

Direct arterial damage and neurovascular unit disruption by mechanical thrombectomy in a rat stroke model

Ryo Sasaki, Toru Yamashita, Koh Tadokoro, Namiko Matsumoto, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF NEUROSCIENCE RESEARCH 98 ( 10 ) 2018 - 2026 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Mechanical thrombectomy (MT) is a standard treatment for acute ischemic stroke that could cause hemorrhagic complications. We aimed to evaluate the pathology of MT-induced arterial damage and neurovascular unit (NVU) disruption in relation to tissue-type plasminogen activator (tPA) injection for acute ischemic stroke. We induced transient middle cerebral artery occlusion in male SHR/Izm rats for 2 hr. This was followed by reperfusion with/without tPA (3 mg/kg) and "rough suture" insertion that mimicked MT once or thrice (MT1 or MT3). Compared with the control group, the tPA + MT3 group presented with an increase in the cerebral infarct and hemorrhage with severer IgG leakage. Moreover, structural damage reaching the tunica media was detected in the MT3 and tPA + MT3 groups. The tPA + MT3 group presented with increased matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression with some MMP9-positive cells expressing a neutrophil marker myeloperoxidase. Furthermore, basal lamina detachment from astrocyte foot processes was observed in the tPA + MT1 and tPA + MT3 groups. These findings suggest that MT causes direct arterial damage, as well as VEGF and MMP9 upregulation, which results in NVU disruption and hemorrhagic complications in acute ischemic stroke, especially when combined with tPA.

DOI： 10.1002/jnr.24671

脳梗塞後に神経細胞を新たに生み出し再生を目指す脳内グリア細胞から神経細胞を誘導する新技術の確立

山下徹, 商敬偉, 中野由美子, 森原隆太, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

神経治療学 37 ( 6 ) S253 - S253 2020.10

幹細胞移植による虚血脳のタンパク分解分子機構への影響

田所功, 福井裕介, 山下徹, 劉夏, 角田慶一郎, 商敬偉, 表芳夫, 武本麻美, 菱川望, 太田康之, 阿部康二

神経治療学 37 ( 6 ) S253 - S253 2020.10

実は見逃されている血管性認知症の危険因子

山下徹, 野崎洋明, 涌谷陽介, 田所功, 野村恵美, 菱川望, 武本麻美, 太田康之, 小野寺理, 阿部康二

Dementia Japan 34 ( 4 ) 493 - 493 2020.10

アルツハイマー病患者の主観的・客観的睡眠障害

田所功, 太田康之, 菱川望, 野村恵美, 涌谷陽介, 高尾芳樹, 表芳夫, 武本麻美, 山下徹, 阿部康二

Dementia Japan 34 ( 4 ) 477 - 477 2020.10

Clinical anticipation of disease onset in a Japanese Asidan (SCA36) family. International journal

Yasuyuki Ohta, Ken Ikegami, Kota Sato, Nozomi Hishikawa, Yoshio Omote, Mami Takemoto, Toru Yamashita, Koji Abe

Journal of the neurological sciences 416 ( 15 ) 117043 - 117043 2020.9

A case of triple seronegative myasthenia gravis with Graves' disease ameliorated after the removal of enlarged thymus with elevated uptake in fluorine-18 fluorodeoxyglucose positron emission tomography

Namiko Matsumoto, Yoshio Omote, Yumiko Nakano, Mami Takemoto, Nozomi Hishikawa, Kota Sato, Yasuyuki Ohta, Toru Yamashita, Tomohiro Toji, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 5 ) 313 - 316 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report on a 35-year-old woman who complained of myasthenia in ocular, bulbar, and limb muscles, but who was negative for antibodies against acetylcholine receptor, muscle-specific kinase, or low-density lipoprotein receptor-related protein 4, accompanied by the suppression of thyroid-stimulating hormone with elevated free T3 and free T4. Administration of edrophonium significantly ameliorated blepharoptosis, and electromyography revealed 13.9% waning after 3 Hz repetitive stimulation in the left accessory nerve. Thus, she was suspected of having triple seronegative myasthenia gravis or thyrotoxic myasthenia. She was remitted after the resection of her enlarged thymus with an elevated uptake in fluorine-18 fluorodeoxyglucose positron emission tomography, suggesting an unknown autoimmune target that escaped detection by current autoantibody screens. Consequently, thymectomy may still be effective in patients with seronegative MG plus hyperthyroidism.

DOI： 10.1111/ncn3.12414

Dynamic changes and mislocalizations of neurodegenerative disease-related proteins in mice stroke model

Xia Liu, Toru Yamashita, Xiaowen Shi, Yuting Bian, Zhihong Bian, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1742 ( 1 ) 146862 2020.9

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

The aggregation and cellular mislocalization of several RNA-binding proteins (RBPs) have been identified as the major hallmarks of neurodegenerative diseases such as frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, it remains obscure whether these pathological changes also occur during cerebral ischemia. In this study, we report that RBPs increased significantly compared with the sham group (*p < 0.05 and **p < 0.01 vs sham), with nuclear depletion and cytoplasmic deposition in neurons in the acute phase of cerebral ischemia. On the other hand, such nucleocytoplasmic mislocalization were not observed in astrocytes. We provide evidence of the alteration of these neurodegeneration-related RBPs after cerebral ischemia, suggesting a potential association between cerebral ischemia and neurodegenerative diseases.

DOI： 10.1016/j.brainres.2020.146862

A unique leukoencephalopathy accompanied by palmoplantar pustulosis with identical pathological feature of helper T cell accumulation.

Sasaki R, Omote Y, Tadokoro K, Matsumoto N, Nomura E, Takemoto M, Hishikawa N, Yamashita T, Ohta Y, and Abe K

Neurology Asia 25 ( 3 ) 415 - 418 2020.9

脳卒中マウスモデルにおけるTocotrienol製剤前投与の治療効果

山下徹, 商敬偉, 馮田, 武本麻美, 菱川望, 太田康之, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 20回 224 - 224 2020.9

Improvement of a decreased anti-oxidative activity by edaravone in amyotrophic lateral sclerosis patients

Yasuyuki Ohta, Toru Yamashita, Emi Nomura, Nozomi Hishikawa, Ken Ikegami, Yosuke Osakada, Namiko Matsumoto, Yuko Kawahara, Taijun Yunoki, Yoshiaki Takahashi, Motonori Takamiya, Koh Tadokoro, Ryo Sasaki, Yumiko Nakano, Keiichiro Tsunoda, Kota Sato, Yoshio Omote, Mami Takemoto, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 415 ( 15 ) 116906 2020.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: The free radical scavenger edaravone is a proven neuroprotective drug for patients with amyotrophic lateral sclerosis (ALS). Our objective was to evaluate the therapeutic effects of edaravone for oxidative stress and anti-oxidative activity in ALS patients.Methods: Twenty-two ALS patients with a disease duration of 2 years, treated by edaravone, and 25 control participants were evaluated according to their clinical scores, including ALS functional rating scale-revised (ALSFRS-R), and serum and cerebrospinal fluid (CSF) markers of oxidative stress dROM and anti-oxidative activity OXY.Results: Serum and CSF markers of anti-oxidative activity OXY were significantly decreased in ALS patients at pre-treatment compared with controls ((##)p < .01), which was improved in the course of edaravone treatment. Both serum and CSF OXY were significantly correlated with ALS clinical scores including ALSFRS-R (*p < .05, **p < .01, ***p < .001). Furthermore, serum OXY at pre-treatment was significantly correlated with a change in the ALSFRS-R score in the sixth cycle of edaravone treatment (*p < .05).Conclusions: The present study suggests significant correlations between anti-oxidative activity and ALS clinical severity, and the therapeutic efficacy of edaravone for decreased anti-oxidative activity in ALS.

DOI： 10.1016/j.jns.2020.116906

Antioxidative effects of a novel dietary supplement Neumentix in a mouse stroke model. International journal

Yuki Taira, Toru Yamashita, Yuting Bian, Jingwei Shang, Namiko Matsumoto, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Keiichiro Tsunoda, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 29 ( 8 ) 104818 - 104818 2020.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: During an acute stroke, reactive oxygen species are overproduced and the endogenous antioxidative defense systems are disrupted. Therefore, antioxidative therapy can be a promising scheme to reduce the severity of stroke. Neumentix is a novel antioxidative supplement produced from a patented mint line and contains a high content of rosmarinic acid (RA). Although Neumentix has proven diverse efficacy and safety in clinical trials, its effect on strokes is unclear. METHODS: Mice that were treated with Neumentix or vehicle for 14 days underwent transient middle cerebral artery occlusion (tMCAO) for 60 min. Mice were sacrificed 5 days after tMCAO. RESULTS: Neumentix preserved body weight after tMCAO, showed a high antioxidative effect in serum, and reduced infarction volume compared to the vehicle. The expression of 4-hydroxy-2-nonenal, Nε-(carboxymethyl) lysine, and 8-hydroxy-2'-deoxyguanosine was reduced in Neumentix-treated mice. CONCLUSION: The antioxidative effect of Neumentix was confirmed. This is the first report to demonstrate the antioxidative effect of Neumentix on strokes.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104818

PDDとDLBの認知機能と情動機能、脳血流画像の比較

武本麻美, 田所功, 表芳夫, 菱川望, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 111 - 112 2020.7

Up-regulation of sphingosine-1-phosphate receptors and sphingosine kinase 1 in the peri-ischemic area after transient middle cerebral artery occlusion in mice

Namiko Matsumoto, Toru Yamashita, Jingwei Shang, Tian Feng, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Emi Nomura, Keiichiro Tsunoda, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1739 ( 15 ) 146831 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

There is thought to be a strong relationship between sphingosine-1-phosphate (S1P) signaling and pathophysiolosy of cerebral ischemia. We examined the change of expression and distribution of SIP receptors (S1PRs) and sphingosine kinases (SphKs) after cerebral ischemia in male C57BL6/J mice using immunohistochemical analysis at 1, 5, 14, and 28 days after 30 min of transient middle cerebral artery occlusion (tMCAO). S1PR1, 3, and 5 were transiently induced in the cells, which were morphologically similar to neurons in the pert-infarct lesion with a peak seen at 1 day after tMCAO (p < 0.01 vs. sham control). S1PR2 appeared in the inner layer of vessels in the ischemic core (p < 0.01 vs. sham control) and the pert-infarct lesion (p < 0.01 vs. sham control) at the acute phase after tMCAO. However, SphK1 was strongly induced at 1 and 5 days after tMCAO (p < 0.01 vs. sham control) in the peri-infarct lesion, whereas SphK2 expression did not change. Western blot analysis at 1 and 5 days after 30 min of tMCAO revealed that the expression of S1PRs were transiently enhanced at the acute phase, which was consistent with the immunohistochemical results. Double immunofluorescent analysis revealed S1PR2/NG2- and S1PR2/CD31-, S1PR3/CD31-, and S1PR5/CD31-double positive cells in the peri-infarct lesion 1 day after tMCAO. The present results suggest that S1PRs and SphK1 may be important therapeutic targets for rescuing the pert-infarct lesion.

DOI： 10.1016/j.brainres.2020.146831

Adult-onset frequent non-convulsive status epilepticus in a patient with ring chromosome 20 syndrome

Xia Liu, Yoshio Omote, Ken Ikegami, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 4 ) 202 - 204 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report a 31-year-old woman with ring chromosome 20 syndrome who presented with epilepsy staring from 16 years old and loss of consciousness from 30 years old. Her neurological examinations and psychological testing were normal, without dysmorphic features. No abnormalities were found in neuroimaging. Electroencephalogram recording showed typical non-convulsive status epilepticus associated with alteration of consciousness. Her diagnosis was based on the cytogenetic analysis indicating that her karyotype was 46, XX, r(20)(p13q13.3)[9]/46, XX[21]. She had refractory epilepsy and improved by a combination of valproate and lacosamide.

DOI： 10.1111/ncn3.12389

Familial dropped head syndrome with extremity muscle weakness

Keiichiro Tsunoda, Nozomi Hishikawa, Yoshio Omote, Ken Ikegami, Yumiko Nakano, Kota Sato, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 4 ) 189 - 191 2020.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report a new case of familial dropped head syndrome (DHS) due to myopathy. The proband is a 63-year-old woman, and her younger sister and son also showed DHS. She was not good at sport since elementary school and showed unique muscle weakness in her paraspine and four limbs. A blood test showed a slight increase in creatine kinase (237 IU/mL) and myoglobin (95 ng/mL). An electromyogram showed myogenic change, and computed tomography revealed a normal muscle volume of the neck but paraspinal muscle atrophy. Muscle biopsy of the right femoral muscle found type 2 fiber atrophy. Based on these unique clinical features, this is the first report of familial DHS which probably due to congenital myopathy.

DOI： 10.1111/ncn3.12382

抗酸化サプリメントTwendee Xの軽度認知障害に対する効果についての検討

松本菜見子, 田所功, 森原隆太, 太田康之, 菱川望, 川野公子, 武本麻美, 山下徹, 犬房春彦, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 113 - 113 2020.7

PDDとDLBの認知機能と情動機能、脳血流画像の比較

武本麻美, 田所功, 表芳夫, 菱川望, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 111 - 112 2020.7

"もの忘れ外来"通院患者の通院脱落に関わる因子

菱川望, 表芳夫, 武本麻美, 太田康之, 山下徹, 阿部康二

日本老年医学会雑誌 57 ( Suppl. ) 112 - 112 2020.7

Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice

Koh Tadokoro, Yusuke Fukui, Toru Yamashita, Xia Liu, Keiichiro Tsunoda, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Feng Tian, Ryo Sasaki, Namiko Matsumoto, Emi Nomura, Xiaowen Shi, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 29 ( 5 ) 104743 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. Methods: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). Results: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. Conclusions: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104743

Diabetic painful truncal neuropathy with hypohidrosis and facial palsy

Keiichiro Tsunoda, Yoshio Omote, Nozomi Hishikawa, Ken Ikegami, Yumiko Nakano, Kota Sato, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Kentaro Deguchi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 155 - 157 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Truncal neuropathy is a rare phenotype of diabetic neuropathy. Here, we report the first case of diabetic painful truncal neuropathy complaining of back pain with hypohidrosis confirmed by a sweat test accompanied by cranial nerve palsy. The patient had poorly controlled type 2 diabetes mellitus and suffered from back pain followed by facial palsy. After pulse therapy with methylprednisolone facial palsy improved, but back pain was intractable with a loss of body weight. The sweat test showed hypohidrosis on the back and soles on his feet. Sural nerve biopsy revealed decreased small fibers and mild axonopathy. After palliative therapy, his symptoms gradually improved.

DOI： 10.1111/ncn3.12370

A spontaneous recovery of anti-galactocerebroside antibody-associated encephalitis without evidence of Mycoplasma infection

Koh Tadokoro, Yoshio Omote, Yosuke Osakada, Ken Ikegami, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 3 ) 164 - 166 2020.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Anti-galactocerebroside (Gal-C) antibody is characteristic of encephalomyelitis and Guillain-Barre syndrome subsequent to mycoplasma infection. Here, we report a 75-year-old Japanese man who presented somnolence, signs of meningeal irritation, and parkinsonian features with positive serum inflammatory markers and cerebrospinal fluid (CSF) pleocytosis. Although anti-Mycoplasma pneumoniae antibody was negative, anti-Gal-C antibody was later detected in his serum. The present case recovered spontaneously without any other specific therapies.

DOI： 10.1111/ncn3.12379

Discrepancy of subjective and objective sleep problems in Alzheimer's disease and mild cognitive impairment detected by a home-based sleep analysis

Koh Tadokoro, Yasuyuki Ohta, Nozomi Hishikawa, Emi Nomura, Yosuke Wakutani, Yoshiki Takao, Yoshio Omote, Mami Takemoto, Toru Yamashita, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 74 76 - 80 2020.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

There is a strong relationship between Alzheimer's disease (AD) and sleep problems, and a sleep condition is informative for evaluating the AD status. In the present study, we evaluated subjective sleep problems in AD and mild cognitive impairment (MCI) with self-check questionnaires and objective sleep problems with a convenient home-based portable device, WatchPAT. A total of 63 subjects with normal cognition (NC) (n = 22), MCI (n = 20), and AD (n = 21) were cross-sectionally investigated. AD patients showed a better self-check Pittsburgh sleep quality index (PSQI) score (*p < 0.05) than NC and MCI patients. On the other hand, WatchPAT analysis showed a significantly reduced rapid eye movement (REM) sleep (*p < 0.05) and increased light sleep in AD patients (*p < 0.05) compared with NC subjects, and mildly reduced REM and increased light sleep in MCI subjects. The present study revealed a gap between the subjective self-check sleep questions and the objective WatchPAT analysis in AD patients. Thus, a home-based sleep study with WatchPAT is a useful tool to detect an objective sleep problem in AD and the risk of MCI conversion into AD. (C) 2020 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2020.01.085

A unique case of myasthenia gravis mimicking Garcin’s syndrome.

Tadokoro K, Hishikawa N, Ikegami K, Nomura E, Kawahara Y, Omote Y, Takemoto M, Yamashita T, Abe K

Neurol Clin Neurosci 1 - 4 2020.4

Delayed Serial Microvascular Injury and Cognitive Decline After Whole Brain Irradiation.

Osakada Y, Yamashita T, Ikegami K, Kawahara Y, Omote Y, Hishikawa N, Takemoto M, Ohta Y, Abe K

Japanese Society of Vascular Cognitive Impairment 6 23 - 26 2020.4

A juvenile case of idiopathic hypertrophic pachymeningitis involved cavernous sinus and proximal trigeminal nerve

Zhihong Bian, Yoshio Omote, Koh Tadokoro, Ken Ikegami, Yosuke Osakada, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 82 - 85 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Idiopathic hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterized by local or diffuse thickening of the cranial or spinal dura mater, which is primarily reported in adults. Here, we report a juvenile idiopathic HP case presenting diplopia and multiple cranial nerve palsies. Although cranial magnetic resonance imaging (MRI) shows evident lesions in cavernous sinus and preganglionic segment of trigeminal nerve, only cerebrospinal fluid (CSF) showed elevated protein (55 mg/dL) and myelin basic protein (MBP, 355 pg/mL) but negative systemic inflammatory markers. Steroid therapy greatly improved the symptom and the CSF data in 1 month.

DOI： 10.1111/ncn3.12355

LGI1 antibody-associated limbic encephalitis started from unilateral basal ganglia to medial temporal lobe and insula

Xia Liu, Yoshio Omote, Yosuke Osakada, Koh Tadokoro, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 68 - 71 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis is a rare autoimmune encephalitis. Here, we report a 39-year-old woman presented with generalized tonic-clonic seizures, night delirium, bilateral upper limb tremor, and hyponatremia. Her symptoms did not improve with initial steroid therapy, and brain magnetic resonance imaging (MRI) showed a progression of abnormalities from right basal ganglia to medial temporal lobe and insula. The presence of LGI1 antibodies in the patient's serum confirmed the clinical diagnosis. After the combined treatments of methylprednisolone, plasma exchange, and intravenous immunoglobulin, her clinical symptoms resolved completely.

DOI： 10.1111/ncn3.12351

A unique case with positive anti-myelin oligodendrocyte glycoprotein antibody presenting multiple brain lesions

Namiko Matsumoto, Kota Sato, Nozomi Hishikawa, Yuko Kawahara, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Kentaro Fujii, Kazuhiko Kurozumi, Isao Date, Toshiyuki Takahashi, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 2 ) 92 - 95 2020.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The accurate diagnosis of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases is sometimes challenging due to its various central nervous system (CNS) lesions. Here, we report a 22-year-old man with positive anti-MOG antibody presenting multiple brain lesions including a brainstem tumefactive demyelinating lesion (TDL), cortical edematous lesions, and a periventricular white matter lesion. These variety of lesions made the diagnosis challenging, especially because TDL is quite rare among MOG antibody-associated disease patients. The present case suggests the importance to check anti-MOG antibody for patients presenting atypical multiple CNS lesions.

DOI： 10.1111/ncn3.12364

Different clinical and neuroimaging features of Japanese dementia siblings with a new N-terminal mutation (Val225Ala) of APP gene

Yasuyuki Ohta, Nozomi Hishikawa, Ken Ikegami, Kota Sato, Yosuke Osakada, Mami Takemoto, Toru Yamashita, Yoshio Omote, Takeshi Ikeuchi, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 72 482 - 484 2020.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Autosomal dominant amyloid precursor protein (APP) mutations in familial Alzheimer's disease accelerate the amyloid beta (A beta) pathology. Here we describe Japanese siblings with a new N-terminal mutation (a heterogeneous c.674T>C, p.Val225Ala) of the APP gene, developing a progressive dementia at 57 years and A beta and tau pathologies in cerebrospinal fluid studies. However, the brother and sister showed different clinical and neuroimaging features, suggesting different A beta pathologies for each sibling. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2019.11.009

Molecular switching from ubiquitin-proteasome to autophagy pathways in mice stroke model

Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 40 ( 1 ) 214 - 224 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE PUBLICATIONS INC

The ubiquitin-proteasome system (UPS) and autophagy are two major pathways to degrade misfolded proteins that accumulate under pathological conditions. When UPS is overloaded, the degeneration pathway may switch to autophagy to remove excessive misfolded proteins. However, it is still unclear whether and how this switch occurs during cerebral ischemia. In the present study, transient middle cerebral artery occlusion (tMCAO) resulted in accelerated ubiquitin-positive protein aggregation from 0.5 h of reperfusion in mice brain after 10, 30 or 60 min of tMCAO. In contrast, significant reduction of p62 and induction of LC3-II were observed, peaking at 24 h of reperfusion after 30 and 60 min tMCAO. Western blot analyses showed an increase of BAG3 and HDAC6 at 1 or 24 h of reperfusion that was dependent on the ischemic period. In contract, BAG1 decreased at 24 h of reperfusion after 10, 30 or 60 min of tMCAO after double immunofluorescent colocalization of ubiquitin, HSP70, p62 and BAG3. These data suggest that a switch from UPS to autophagy occurred between 10 and 30 min of cerebral ischemia depending on the BAG1/BAG3 ratio and level of HDAC6.

DOI： 10.1177/0271678X18810617

A dramatic increase in serum CK levels after switching from oral to intravenous administration of LEV

Mami Takemoto, Taijun Yunoki, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Jingwei Shang, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 8 ( 1 ) 39 - 41 2020.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The authors report on a 22-year-old Japanese woman who started oral administration of 1000 mg levetiracetam (LEV) for her epilepsy after the second convulsive seizure. She was free from seizures for the subsequent 111 days, but a third tonic-clonic seizure happened and she was transferred to our hospital (Day 1). Her consciousness state was drowsy and 1000 mg LEV continued for two days, but intravenously. Although her state became clear, her serum creatine kinase (CK), myoglobin (Mb), and creatine (Cre) levels were significantly elevated (18 179 IU/L, 2783 ng/mL, and 0.8 mg/mL) with a peak at Day 5 of CK 26, 189 IU/L. After stopping intravenous injection of LEV, serum CK returned to its normal level promptly. The present case suggests that we should take more care in monitoring for rhabdomyolysis on switching from oral to intravenous administration of LEV.

DOI： 10.1111/ncn3.12336

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology

Koji Abe, Jingwei Shang, Xiaowen Shi, Toru Yamashita, Nozomi Hishikawa, Mami Takemoto, Ryuta Morihara, Yumiko Nakano, Yasuyuki Ohta, Kentaro Deguchi, Masaki Ikeda, Yoshio Ikeda, Koichi Okamoto, Mikio Shoji, Masamitsu Takatama, Motohisa Kojo, Takeshi Kuroda, Kenjiro Ono, Noriyuki Kimura, Etsuro Matsubara, Yosuke Osakada, Yosuke Wakutani, Yoshiki Takao, Yasuto Higashi, Kyoichi Asada, Takehito Senga, Lyang Ja Lee, Kenji Tanaka

Journal of Alzheimer's Disease 73 ( 1 ) 217 - 227 2020

Publishing type：Research paper (scientific journal)

© 2020-IOS Press and the authors. All rights reserved. Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid-β (Aβ), plasma tau, and serum antibodies for Aβ1-42 are not yet well established. Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology. Methods: With only 1.5μl of serum, we examined a new target plate 'BLOTCHIP®' plus a matrix-Assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n=100), MCI (n=60), and AD (n=99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains. Results: Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (∗∗∗p<0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains. Conclusion: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.

DOI： 10.3233/JAD-191016

A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology

Koji Abe, Jinwei Shang, Xiaowen Shi, Toru hita Yamas, Nozomi Hishikawa, Mami Takemoto, Ryuta Morihara, Yumiko Nakano, Yasuyuki Ohta, Kentaro Deguchi, Masaki Ikeda, Yoshio Ikeda, Koichi Okamoto, Mikio Shoji, Masamitsu Takatama, Motohisa Kojo, Takeshi Kuroda, Kenjiro Ono, Noriyuki Kimura, Etsuro Matsubara, Yosuke Osakada, Yosuke Wakutani, Yoshiki Takao, Yasuto Higashi, Kyoichi Asada, Takehito Senga, Liang-Ja Lee, Kenji Tanaka

JOURNAL OF ALZHEIMERS DISEASE 73 ( 1 ) 217 - 227 2020

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid-beta(A beta), plasma tau, and serum antibodies for A beta(1-42 )are not yet well established.Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.Methods: With only 1.5 mu l of serum, we examined a new target plate "BLOTCHIP (R)" plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.Results: Apart from A beta or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain A beta deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains.Conclusion: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage.

DOI： 10.3233/JAD-191016

A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption. International journal

Yuting Bian, Toru Yamashita, Yuki Taira, Jingwei Shang, Keiichiro Tsunoda, Tian Feng, Ryo Sasaki, Xia Liu, Xiaowen Shi, Koh Tadokoro, Emi Nomura, Namiko Matsumoto, Yusuke Osakada, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Current neurovascular research 17 ( 3 ) 286 - 293 2020

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. METHODS: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. RESULTS: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. CONCLUSION: The present study provided an evidence of Neumentix's anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

DOI： 10.2174/1567202617666200517105727

Early Emergence of Neuropsychiatric Symptoms in Cognitively Normal Subjects and Mild Cognitive Impairment

Keiichiro Tsunoda, Toru Yamashita, Yosuke Osakada, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Emi Nomura, Ryuta Morihara, Yumiko Nakano, Yoshiaki Takahashi, Noriko Hatanaka, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 73 ( 1 ) 209 - 215 2020

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

The world is rapidly aging and facing an increase in the number of dementia patients, so it is important to detect the preclinical stage of dementia in such countries. We examined both cognitive and affective functions among cognitively normal control (n = 218), mild cognitive impairment (MCI, n = 146), and Alzheimer's disease (AD, n = 305) subjects using two evaluation tools for behavioral and psychological symptoms of dementia (BPSD) [Abe's BPSD score (ABS) and mild behavioral impairment (MBI)]. BPSD were present in 12.4% (ABS) and 9.6% (MBI) of cognitively normal people, 34.9% and 32.2% in MCI subjects, and 66.2% and 51.1% in AD patients. Both ABS (p < 0.05) and MBI (( )p < 0.01) score showed worse score with cognitive decline of the Mini-Mental State Examination in the AD group in BPSD-positive participants. Similar correlations were found in all participants in AD group ((parallel to parallel to)p < 0.01 versus ABS and MBI). Among the subscales in BPSD-positive participants, an apathy/indifference score of ABS and a decreased motivation of MBI showed significant differences in AD patients compared to the control and MCI subjects (**p < 0.01). In addition, subscale analyses further showed a downward trend from the control to MCI and AD subjects in four ABS subscales and three MBI subscales. The present study showed the preclinical presence of BPSD in cognitively normal people, more so in MCI subjects, and ABS detected BPSD more sensitively than MBI in all three groups.

DOI： 10.3233/JAD-190669

The Efficacy of Sertraline, Escitalopram, and Nicergoline in the Treatment of Depression and Apathy in Alzheimer's Disease: The Okayama Depression and Apathy Project (ODAP). International journal

Mami Takemoto, Yasuyuki Ohta, Nozomi Hishikawa, Toru Yamashita, Emi Nomura, Keiichiro Tsunoda, Ryo Sasaki, Koh Tadokoro, Namiko Matsumoto, Yoshio Omote, Koji Abe

Journal of Alzheimer's disease : JAD 76 ( 2 ) 769 - 772 2020

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Neuropsychiatric symptoms of dementia such as depression and apathy in patients with Alzheimer's disease (AD) are associated with a lower quality of life. OBJECTIVE: We aimed to determine the efficacy of two antidepressants and one antipathy drug in the treatment of depression and apathy in AD patients. METHODS: In the present study, we evaluated the efficacy of sertraline (n = 11; average dose = 31.8 mg), escitalopram (n = 13; average dose = 7.3 mg), and nicergoline (n = 9; average dose = 14.5 mg) in treating depression and apathy over a period of 3 months (M).The 33 patients with AD demonstrated high Geriatric Depression Scale (GDS) (>5) or a high Apathy Scale (AS) (>16) scores. RESULTS: The patients receiving escitalopram treatment showed a significant improvement in GDS score from baseline (8.2±3.5) to 3 M (5.7±2.6, p = 0.04), and the patients receiving sertraline treatment showed a significant improvement in AS score from baseline (20.8±5.2) to 3 M (16.8±6.1, p = 0.05); however, no significant changes were noted in patients receiving nicergoline. CONCLUSION: These results provide novel information on the efficacy of sertraline and escitalopram in the treatment of apathy and depression, respectively, in patients with AD.

DOI： 10.3233/JAD-200247

Female dominant association of sarcopenia and physical frailty in mild cognitive impairment and Alzheimer's disease

Yasuyuki Ohta, Emi Nomura, Noriko Hatanaka, Yosuke Osakada, Namiko Matsumoto, Ryo Sasaki, Keiichiro Tsunoda, Mami Takemoto, Koh Tadokoro, Nozomi Hishikawa, Yosuke Wakutani, Toru Yamashita, Kota Sato, Yoshio Omote, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 70 96 - 101 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Associations of sarcopenia and physical frailty in cognitive and affective (depression, apathy, and behavioral and psychological symptoms of dementia) functions of mild cognitive impairment (MCI) and Alzheimer's disease (AD) were not fully evaluated previously, especially not for gender differences. 165 AD, 84 MCI, and 48 control participants (175 female, 122 male) were evaluated for cognitive, affective, activities of daily living (ADL), and physical functions associated with sarcopenia and physical frailty. In both sexes, cognitive and affective functions, ADL, and physical functions worsened in MCI and AD compared to control subjects. Physical dysfunctions, especially slow gait speed (3 m up and go test), were significantly associated with cognitive, affective, and ADL declines in participants (control subjects, MCI, and AD) of each gender, which were especially noticeable in females. The present study may be the first to suggest significant associations of sarcopenia and physical frailty with cognitive and affective functions of MCI and AD, especially in females. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2019.08.062

Intracranial invasive fungal aneurysm due to Aspergillus sinusitis successfully treated by voriconazole plus internal carotid artery ligation therapy in an aged woman

Mami Takemoto, Yasuyuki Ohta, Koh Tadokoro, Ryo Sasaki, Yoshiaki Takahashi, Kota Sato, Toru Yamashita, Nozomi Hishikawa, Jingwei Shang, Masafumi Hiramatsu, Kenji Sugiu, Tomohito Hishikawa, Isao Date, Koji Abe

NEUROLOGY ASIA 24 ( 4 ) 363 - 367 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ASEAN NEUROLOGICAL ASSOC

A fungal carotid aneurysm is an infrequently occurring infectious aneurysm that is usually treated by antifungal therapy plus surgical debridement of the infected vessel. We herein report an extremely rare case involving a patient with a medical history of bladder cancer treated by Bacillus Calmette-Guerin (BCG) who developed a fungal aneurysm of the internal carotid artery and thrombosis of the superior ophthalmic vein caused by maxillary Aspergillus sinusitis. The patient was successfully treated by antifungal, anticoagulant, and antiplatelet drugs combined with internal carotid artery ligation therapy. Internal carotid artery fungal aneurysm is associated with a high mortality rate, but the present case suggests that it can be successfully treated by antifungal therapy combined with a less invasive endovascular therapy.

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people

Nozomi Hishikawa, Yoriko Takahashi, Yusuke Fukui, Ryo Tokuchi, Junichi Furusawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Koji Abe

Neurological Research 41 ( 11 ) 1001 - 1007 2019.11

Language：English Publishing type：Research paper (scientific journal)

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga (‘Yoga-plus’) among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ± 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe’s behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ≥ 5) and AS (AS ≥ 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

DOI： 10.1080/01616412.2019.1672380

Spastic Paraplegia Accompanied by Extrapyramidal Sign and Frontal Cognitive Dysfunction.

Ryo Sasaki, Yasuyuki Ohta, Kota Sato, Koh Tadokoro, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Hiroyuki Ishiura, Shoji Tsuji, Koji Abe

Internal medicine (Tokyo, Japan) 58 ( 21 ) 3163 - 3165 2019.11

Language：English Publishing type：Research paper (scientific journal)

A complicated form of spastic paraplegia is a neurodegenerative disorder presenting as progressive spasticity in the bilateral lower limbs accompanied by some clinical features. The present case showed spastic paralysis and hyperreflexia in all extremities as well as lead pipe rigidity in the neck and bilateral upper extremities (R < L), decreased scores on frontal cognitive tests, a decreased accumulation of the right dorsal putamen on a DAT scan, and hypoperfusion of the bilateral frontal lobes on 99mTc-ECD single photon emission computed tomography (SPECT). The present case provides a new spectrum of spastic paraplegia based on the evidence of clinical scores and the findings of brain functional imaging.

DOI： 10.2169/internalmedicine.2765-19

時間で追う脳虚血の病態と治療:(2)亜急性期虚血脳内グリア細胞から神経細胞を誘導するダイレクトリプログラミング法の確立

山下徹, 商敬偉, 中野由美子, 森原隆太, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

脳循環代謝 31 ( 1 ) 65 - 65 2019.11

パーキンソン病とレビー小体型認知症の検査所見やmicrobleeds出現頻度の違いについて

武本麻美, 佐藤恒太, 太田康之, 山下徹, 菱川望, 阿部康二

臨床神経学 59 ( Suppl. ) S266 - S266 2019.11

Chronic cerebral hypoperfusion alters amyloid-beta transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse

Jingwei Shang, Tom Yamashita, Feng Tian, Xianghong Li, Xia Liu, Xiaowen Shi, Yumiko Nakano, Keiichiro Tsunoda, Emi Nomura, Ryo Sasaki, Koh Tadokoro, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

BRAIN RESEARCH 1723 146379 - 146379 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Abnormal accumulation of amyloid-beta (A beta) peptide defines progression of Alzheimer's disease (AD) pathology in brain. Here, we investigated expressive changes of two main All transport receptors low-density lipoprotein receptor related protein-1 (LRP1) and receptor for advanced glycation end products (RAGE) in a novel AD mice (APP23) with chronic cerebral hypoperfusion (CCH) model, moreover, examined a protective effect of a free radical scavenger edaravone (Eda). In contrast to wild type (WT) and APP23 mice, CCH strongly accelerated abnormal A beta 40 depositions and cerebral amyloid angiopathy (CAA) pathology, increased both LRP1 and RAGE expressions in brain parenchyma, while a decrease of LRP1 and an increase of RAGE were observed in vascular endothelial cells at age 12 months (M) of AD mice. Furthermore, CCH strongly increased expressions of two hypoxia-related proteins hypoxia inducible factor-1 alpha (HIF-1 alpha) and heme oxygenase-1 (HO-1), two oxidative-related proteins 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and decreased both two vital nutrient transporter proteins major facilitator super family domain containing 2a (Mfsd2a) and glucose transporter 1 (Glut1) expressions. Such the above abnormal pathological changes were significantly ameliorated by edaravone treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology causing double imbalances of A beta efflux and influx transport related proteins in the cortical blood vessels in AD mice, and that such a neuropathologic abnormality was greatly ameliorated by Eda.

DOI： 10.1016/j.brainres.2019.146379

A unique stroke case with contralateral sulcal hyperintensity on fluid-attenuated inversion recovery image changed to linear serpiginous structures

Yosuke Osakada, Yoshiaki Takahashi, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 6 ) 351 - 353 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

An 83-year-old man developed acute ischemic stroke. Brain magnetic resonance imaging (MRI) showed ischemic stroke in the left parietal lobe gyri, but fluid-attenuated inversion recovery (FLAIR) showed hyperintensity in the contralateral right temporal-occipital lobe sulci. Follow-up FLAIR image showed the gradual disappearance of the sulcal hyperintensity in the sulci and changed to linear serpiginous structures. This is a unique stroke case showing transitioned FLAIR findings suggesting that the sulcal hyperintensity findings are more severe and an earlier ischemic condition than the linear serpiginous structures.

DOI： 10.1111/ncn3.12327

Yoga-plus exercise mix promotes cognitive, affective, and physical functions in elderly people

Nozomi Hishikawa, Yoriko Takahashi, Yusuke Fukui, Ryo Tokuchi, Junichi Furusawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGICAL RESEARCH 41 ( 11 ) 1001 - 1007 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Objectives: Increased attention is being paid to Asian medicine in balanced total health care. We investigated the effects of mixed exercise including yoga (?Yoga-plus?) among elderly individuals. Methods: A total of 385 subjects (72 males and 313 females, 75.5 ? 8.7 years old) participated in a 12-month (M) exercise program at a health and welfare center, a day service center, and a nursing home. Cognitive, affective, and physical functions, and activities of daily living (ADL), were compared at baseline (0M), 6M and 12M of exercise intervention. Results: Mean scores on the frontal assessment battery, clock drawing test, cube copying test, letter fluency, and category fluency significantly improved after the Yoga-plus intervention, while mini-mental state examination, Hasegawa dementia score-revised, and trail-making test performance were relatively stable. Affective scores on the geriatric depression scale (GDS), apathy scale (AS) and Abe?s behavioral and psychological symptoms of dementia were not significantly affected by exercise therapy, but subgroups with higher baseline GDS (GDS ? 5) and AS (AS ? 16) scores showed a significant improvement after intervention. One-leg standing time and 3-m timed up and go test performance significantly improved after 12M intervention. Discussion: Yoga-plus improved cognitive, affective, ADL, and physical functions in a local elderly population, particularly among below-baseline individuals, indicating the benefits of dementia prevention among elderly individuals.

DOI： 10.1080/01616412.2019.1672380

A Japanese patient with a VCP mutation c.290G > A (p.G97E) presenting a rapid progressive respiratory failure Reviewed

Emi Nomura, Yasuyuki Ohta, Kota Sato, Yuko Kawahara, Mami Takemoto, Yoshiaki Takahashi, Namiko Matsumoto, Taijun Yunoki, Toru Yamashita, Nozomi Hishikawa, Ichizo Nishino, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 6 ) 361 - 364 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disorder caused by mutations in the valosin-containing protein (VCP) gene. IBMPFD usually presents progressive limb muscle weakness resulting in wheelchaired after mean course of 9 years with myopathy, and Paget's osteolytic lesions and frontotemporal dementia (FTD) rarely present respiratory failure. Different from previous reports, we reported a Japanese IBMPFD patient with a VCP mutation c.290G > A (p.G97E), presenting a progressive respiratory failure accompanied by wheelchaired in only 6 years after myopathy onset, suggesting unique relationship between clinical severity and c.290G > A (p.G97E) mutation of VCP gene in Japanese.

DOI： 10.1111/ncn3.12330

見逃したくない治療可能な小脳性運動失調症 PEX10変異による小脳失調症

山下徹, 三井純, 下澤伸行, 高島茂雄, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 松川敬志, 石浦浩之, 吉村淳, 土井晃一郎, 森下真一, 辻省次, 阿部康二

臨床神経学 59 ( Suppl. ) S45 - S45 2019.11

パーキンソン病とレビー小体型認知症の検査所見やmicrobleeds出現頻度の違いについて

武本麻美, 佐藤恒太, 太田康之, 山下徹, 菱川望, 阿部康二

臨床神経学 59 ( Suppl. ) S266 - S266 2019.11

筋萎縮性側索硬化症患者の前頭葉機能の特徴

太田康之, 山下徹, 菱川望, 佐藤恒太, 武本麻美, 表芳夫, 阿部康二

Dementia Japan 33 ( 4 ) 529 - 529 2019.10

多発性の大脳・脳幹病変を認め、診断及び治療に苦慮した抗MOG抗体関連症候群の1例

松本菜見子, 佐藤恒太, 河原由子, 武本麻美, 菱川望, 表芳夫, 商敬偉, 太田康之, 山下徹, 藤井謙太郎, 黒住和彦, 伊達勲, 阿部康二

神経治療学 36 ( 6 ) S251 - S251 2019.10

アルツハイマー病の進行に関する臨床的予測因子(Clinical predictors of Alzheimer's disease progression)

菱川望, 表芳夫, 武本麻美, 太田康之, 山下徹, 阿部康二

Dementia Japan 33 ( 4 ) 523 - 523 2019.10

Sleep problems in subacute myelo-optico neuropathy (SMON)

Nozomi Hishikawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Kenichi Sakai, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 68 128 - 133 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Subacute myelo optico neuropathy (SMON) patients typically suffer from sequelae that cause sleep disturbances. We sought to examine the prevalence of sleep problems among SMON patients. We conducted a questionnaire-based survey concerning sleep problems among 106 SMON patients, and 110 age- and gender-matched control participants. The prevalence of subjective insomnia (6 <= Athens Insomnia Scale score) was 89.6% among SMON patients, which was significantly higher than among control participants 54.4%. Sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) revealed that the prevalence of poor sleepers (6 <= PSQI score) was higher among SMON patients than control participants (75.6% vs 39.6%, respectively). Subscale analyses of rapid eye movement sleep behavior disorder screening questionnaire revealed that scores on two items ("dreams match nocturnal behavior" and "limb movements") were significantly higher among SMON patients than control participants. In addition, daytime sleepiness scores were significantly higher among SMON patients than control participants (4 <= Epworth Sleepiness Scale scores: 54.0% vs 29.0%, respectively). The current study revealed that most SMON patients suffer from insomnia with dissatisfactory sleep quality, likely due to their long-term physical sequelae. Moreover, SMON patients showed higher rates of daytime sleepiness and sleep medication intake, which could be related to reduced activity during the day, as well as insomnia. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2019.07.013

Sleep problems in subacute myelo-optico neuropathy (SMON)

Nozomi Hishikawa, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Kenichi Sakai, Koji Abe

Journal of Clinical Neuroscience 68 128 - 133 2019.10

Publishing type：Research paper (scientific journal)

© 2019 Elsevier Ltd Subacute myelo-optico neuropathy (SMON) patients typically suffer from sequelae that cause sleep disturbances. We sought to examine the prevalence of sleep problems among SMON patients. We conducted a questionnaire-based survey concerning sleep problems among 106 SMON patients, and 110 age- and gender-matched control participants. The prevalence of subjective insomnia (6 ≤ Athens Insomnia Scale score) was 89.6% among SMON patients, which was significantly higher than among control participants 54.4%. Sleep quality measured with the Pittsburgh Sleep Quality Index (PSQI) revealed that the prevalence of poor sleepers (6 ≤ PSQI score) was higher among SMON patients than control participants (75.6% vs 39.6%, respectively). Subscale analyses of rapid eye movement sleep behavior disorder screening questionnaire revealed that scores on two items (“dreams match nocturnal behavior” and “limb movements”) were significantly higher among SMON patients than control participants. In addition, daytime sleepiness scores were significantly higher among SMON patients than control participants (4 ≤ Epworth Sleepiness Scale scores: 54.0% vs 29.0%, respectively). The current study revealed that most SMON patients suffer from insomnia with dissatisfactory sleep quality, likely due to their long-term physical sequelae. Moreover, SMON patients showed higher rates of daytime sleepiness and sleep medication intake, which could be related to reduced activity during the day, as well as insomnia.

DOI： 10.1016/j.jocn.2019.07.013

Twendee X Ameliorates Phosphorylated Tau, alpha-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion

Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 28 ( 10 ) 104310 - 104310 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and alpha-synudein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX). Methods: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry. Results: The present study revealed that the expressions of phospho-tau and phospho-alpha-synudein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and **P < .01 versus WT; P-# < .05 and (##) P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (*P < .01 versus WT; (#) P < .05, and (##) P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/ day, from 4.5 to 12 months) significantly reduced tau and oc-synudein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group. Conclusions: Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.104310

胃瘻造設後に高浸透圧高血糖症候群を発症した進行性核上性麻痺の1例

田所功, 佐藤恒太, 森原隆太, 商敬偉, 武本麻美, 表芳夫, 太田康之, 山下徹, 菱川望, 阿部康二

神経治療学 36 ( 6 ) S269 - S269 2019.10

Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice

Xiaowen Shi, Yasuyuki Ohta, Xia Liu, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Tian Feng, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

NEUROSCIENCE 416 126 - 136 2019.9

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Alzheimer's disease (AD) in the elderly is frequently accompanied by chronic cerebral hypoperfusion (CCH), which impairs the clearance of amyloid beta (A beta) due to the dysfunction of the blood-brain barrier (BBB) and accelerates the AD pathology. Since the coagulation and complement cascades are associated with BBB dysfunction and AD pathology, we investigated the expression changes of coagulation (fibrinogen alpha chain-FGA, coagulation factor XIII A chain-Factor XIII alpha) and complement (plasma protease C1 inhibitor-C1-INH, Complement component 3-C3) factors in the brain of novel AD model (APP23) mice with CCH at 12 months of age. Immunohistochemical and immunofluorescent analysis showed that the expressions of FGA, Factor XIII alpha, C1-INH and C3 were significantly increased in cerebral neocortex, hippocampus, and thalamus of APP23 + CCH group (n = 12) as compared with wild type (WT, n = 10) and APP23 (n = 10) groups (*P < . 05 and ** P < .01 vs WT; P-# < .05 and P-## < .01 vs APP23), especially near and inside of neurovascular unit. The present study suggests that CCH activated both the coagulation and complement cascades in a novel AD model mice brain accompanied by the acceleration of AD pathology. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2019.07.050

Late presented congenital myasthenic syndrome with novel compound heterozygous CHRNE mutations mimicking seronegative myasthenia gravis

Yumiko Nakano, Keiichiro Tsunoda, Toru Yamashita, Jun Mitsui, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Tatsushi Toda, Shoji Tsuji, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 5 ) 288 - 290 2019.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We found a late presented congenital myasthenic syndrome (CMS) patient with novel CHRNE gene mutations. Although our patient has shown blepharoptosis since youth, fatigable muscle weakness began at age 71. Genetic analysis revealed novel compound heterozygous CHRNE mutations (c.1032+2T>G, c.1306_1307 delGA). His myasthenic symptoms were well managed by oral anti-cholinesterase drug until he died at 82-year-old. The present case showed mild myasthenic symptoms with very late presentation and slow progression. Late presented CMS is often underdiagnosed; therefore, genetic testing is important to distinguish it from other myasthenic disease.

DOI： 10.1111/ncn3.12317

Imaging Hypoxic Stress and the Treatment of Amyotrophic Lateral Sclerosis with Dimethyloxalylglycine in a Mice Model

Emi Nomura, Yasuyuki Ohta, Koh Tadokoro, Jingwei Shang, Tian Feng, Xia Liu, Xiaowen Shi, Namiko Matsumoto, Ryo Sasaki, Keiichiro Tsunoda, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Takahiro Kuchimaru, Shinae Kizaka-Kondoh, Koji Abe

NEUROSCIENCE 415 31 - 43 2019.9

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Hypoxia inducible factor-1 alpha (HIF-1 alpha) is a key transcription factor that maintains oxygen homeostasis. Hypoxic stress is related to the pathogenesis of amyotrophic lateral sclerosis (ALS), and impaired HIF-1 alpha induces motor neuron degeneration in ALS. Dimethyloxalylglycine (DMOG) upregulates the stability of HIF-1 alpha expression and shows neuroprotective effects, but has not been used in ALS as an anti-hypoxic stress treatment. In the present study, we investigated hypoxic stress in ALS model mice bearing G93A-human Cu/Zn superoxide dismutase by in vivo HIF-1 alpha imaging, and treated the ALS mice with DMOG. In vivo HIF-1 alpha imaging analysis showed enhanced hypoxic stress in both the spinal cord and muscles of lower limbs of ALS mice, even at the pre-symptomatic stage. HIF-1 alpha expression decreased as the disease progressed until 126 days of age. DMOG treatment significantly ameliorated the decrease in HIF-1 alpha expression, the degeneration of both spinal motor neurons and myofibers in lower limbs, gliosis and apoptosis in the spinal cord. This was accompanied by prolonged survival. The present study suggests that in vivo bioluminescence resonance energy transfer (BRET) HIF-1 alpha imaging is useful for evaluating hypoxic stress in ALS, and that the enhancement of HIF-1 alpha is a therapeutic target for ALS patients. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2019.06.025

A Japanese patient with a VCP mutation c.290G > A (p.G97E) presenting a rapid progressive respiratory failure.

Nomura E, Ohta Y, Sato K, Kawahara Y, Takemoto M, Takahashi Y, Matsumoto N, Yunoki T, Yamashita T, Hishikawa N, Nishino I, Abe K

Neuro Clin Neurosci 7 ( 6 ) 361 - 364 2019.8

A Unique Recurrent Stroke Case due to Bilateral Vertebral Artery Dissection with Familial Hirschsprung Disease

Kota Sato, Ryo Sasaki, Yasuyuki Ohta, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

Journal of Stroke and Cerebrovascular Diseases 28 ( 8 ) e113 - e115 2019.8

Publishing type：Research paper (scientific journal)

© 2019 Elsevier Inc. Vertebral artery (VA) dissection is one major cause of brain infarction in young and middle-aged adults. Risk factors for VA dissection are hypertension, diabetes mellitus, hyperlipidemia, trauma, and genetic factors. A 32-year-old man with familial Hirschsprung disease at the age of 2 presented cerebellar ischemic stroke due to bilateral VA dissections. A stroke recurred within 17 days despite oral dual antiplatelet therapy. Bilateral VA dissections and recurrent dissections are related to genetic mutations associated with connective tissue diseases. A part of familial Hirschsprung disease has genetic factors in common with cerebrovascular disease. There may be a common genetic background between his VA dissection and Hirschsprung disease.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.04.035

Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion

Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 28 ( 7 ) 1993 - 2002 2019.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-beta accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood. Methods: APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry. Results: In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-beta plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-b pathology and neuronal loss, alleviated neuroinflammation and oxidative stress. Conclusions: The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.

DOI： 10.1016/j.jstrokecerebrovasdis.2019.03.029

In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia

Toru Yamashita, Jingwei Shang, Yumiko Nakano, Ryuta Morihara, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

SCIENTIFIC REPORTS 9 ( 1 ) 10956 - 10956 2019.7

Language：English Publishing type：Research paper (scientific journal) Publisher：NATURE PUBLISHING GROUP

The therapeutic effect of in vivo direct reprogramming on ischemic stroke has not been evaluated. In the present study, a retroviral solution (1.5-2.0 x 10(7) /ul) of mock pMX-GFP (n = 13) or pMX-Ascl1/Sox2/NeuroD1 (ASN) (n = 14) was directly injected into the ipsilateral striatum and cortex 3 days after 30 min of transient cerebral ischemia. The reprogrammed cells first expressed neuronal progenitor marker Dcx 7 and 21 days after viral injection, then expressed mature neuronal marker NeuN. This was accompanied by morphological changes, including long processes and synapse-like structures, 49 days after viral injection. Meanwhile, therapeutic improvement was not detected both in clinical scores or infarct volume. The present study provides a future novel self-repair strategy for ischemic stroke with beneficial modifications of the inducer-suppressor balance.

DOI： 10.1038/s41598-019-47482-0

A pneumococcal meningoencephalitis with a small spleen

Keiichiro Tsunoda, Kota Sato, Yoshiaki Takahashi, Koh Tadokoro, Ryo Sasaki, Emi Nomura, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 4 ) 215 - 217 2019.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Streptococcus pneumoniae is a major cause of bacterial meningitis usually in children or elder adults. We report a case of a 38-year-old man having pneumococcal meningoencephalitis with a small spleen (35 cm(3)), compared to seven previous patients with pneumococcal meningitis in our department. Among the eight patients, four cases were due to sinusitis, but the origin could not be identified in the other four cases, including the present case who was the youngest patient with the smallest splenic size. Of interest in the present analysis was the negative or positive correlation between splenic size and age, with or without sinusitis. This is the first report on pneumococcal meningoencephalitis that takes into consideration age, splenic size, and the origin of infection.

DOI： 10.1111/ncn3.12290

Acceleration of NLRP3 inflammasome by chronic cerebral hypoperfusion in Alzheimer's disease model mouse

Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Xianghong Li, Feng Tian, Xia Liu, Yong Huang, Xiaowen Shi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROSCIENCE RESEARCH 143 61 - 70 2019.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Cerebral neuroinflammation defines a novel pathway for progressing Alzheimer's disease (AD) pathology. We investigated immunohistological changes of neuroinflammation with nucleotide-binding domain and leucine-rich repeat (NLR)-protein 3 (NLRP3), activated caspase-1 and interleukin-1 beta (IL-1 beta) in a novel AD (APP23) mice with chronic cerebral hypoperfusion (CCH) model from 4 months (M) of age, moreover, examined protective effect of galantamine. CCH strongly enhanced NLRP3, activated caspase-1 and IL-1 beta expressions in hippocampus and thalamus at age 12 M of AD mice. CCH also exaggerated amyloid-beta (A beta) 40 depositions in cerebral cortex. Furthermore, CCH exacerbated a marked dissociation of neurovascular unit (NVU). These pathological changes were ameliorated by galantamine treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology including neuroinflammation, A beta accumulations and NVU dissociation in AD mice, which was greatly protected by an allosterically potentiating ligand galantamine. (C) 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2018.06.002

Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis

Yasuyuki Ohta, Emi Nomura, Jingwei Shang, Tian Feng, Yong Huang, Xia Liu, Xiaowen Shi, Yumiko Nakano, Nozomi Hishikawa, Kota Sato, Mami Takemoto, Toru Yamashita, Koji Abe

JOURNAL OF NEUROSCIENCE RESEARCH 97 ( 5 ) 607 - 619 2019.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Oxidative stress is associated with the degeneration of both motor neurons and skeletal muscles in amyotrophic lateral sclerosis (ALS). A free radical scavenger edaravone has been proven as a therapeutic drug for ALS patients, but the neuroprotective mechanism for the oxidative stress of ALS has not been fully investigated. In this study, we investigated oxidative stress in ALS model mice bearing both oxidative stress sensor nuclear erythroid 2-related factor 2 (Nrf2) and G93A-human Cu/Zn superoxide dismutase (Nrf2/G93A) treated by edaravone. In vivo Nrf2 imaging analysis showed the accelerated oxidative stress both in spinal motor neurons and lower limb muscles of Nrf2/G93A mice according to disease progression in addition to the enhancement of serum oxidative stress marker dROMS. These were significantly alleviated by edaravone treatment accompanied by clinical improvements (rotarod test). The present study suggests that in vivo optical imaging of Nrf2 is useful for detecting oxidative stress in ALS, and edaravone alleviates the degeneration of both motor neurons and muscles related to oxidative stress in ALS patients.

DOI： 10.1002/jnr.24368

Very rare solitary primary peripheral nerve onset cytotoxic molecule-positive peripheral T-cell lymphoma (PTCL)

Namiko Matsumoto, Kota Sato, Yoshiaki Takahashi, Yuko Kawahara, Taijun Yunoki, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Maiko Sakamoto, Eisei Kondou, Rei Shibata, Tadashi Yoshino, Toshifumi Ozaki, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 3 ) 146 - 149 2019.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Here we present the first report of solitary primary peripheral nerve onset cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (PTCL) diagnosed after nerve biopsy. An 84-year-old female with rheumatoid arthritis (RA) complained of asymmetric severe tenderness in her upper limbs. The biopsy pathology revealed a direct invasion of CM-positive PTCL. When RA patients complain of numbness, tenderness, or weakness, lymphomatic peripheral nerve invasion should be considered.

DOI： 10.1111/ncn3.12280

Multi-modal combination therapy rescued a frequent ischemic stroke patient due to giant cell arteritis Reviewed

Yoshiaki Takahashi, Kota Sato, Namiko Matsumoto, Yuko Kawahara, Taijun Yunoki, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 7 ( 3 ) 132 - 135 2019.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Ischemic stroke (IS) due to giant cell arteritis (GCA) is rare, but highly mortal. Here, we report a 72-year-old man who showed frequent IS with GCA. Initial therapy with prednisolone increased the frequency of IS, which disappeared after continuous multi-modal combination therapy with corticosteroids, immunosuppressive agents, antiplatelets, and statin. The present case was discharged with independent walk, suggesting that a multi-modal combination therapy rescued the GCA patient from frequent IS.

DOI： 10.1111/ncn3.12266

Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C.

Namiko Matsumoto, Yasuyuki Ohta, Kentaro Deguchi, Masayuki Kishida, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Aki Watanabe, Koutaro Yokote, Minoru Takemoto, Junko Oshima, Koji Abe

Internal medicine (Tokyo, Japan) 58 ( 7 ) 1033 - 1036 2019.4

Language：English Publishing type：Research paper (scientific journal)

Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others.

DOI： 10.2169/internalmedicine.1816-18

A Japanese family of autosomal dominant cerebral small vessel disease with heterozygous HTRA1 mutation showing dementia, gait disturbance and subarachnoid hemorrhage.

Yamashita T, Nozaki H, Wakutani Y, Tadokoro K, Nomura E, Takahashi Y, Sato K, Hishikawa N, Takemoto M, Shang J, Ohta Y, Onodera O, Abe K

Vas-Cog Journal 5 20 - 26 2019.4

Improving Anxiety in Subacute Myelo-optico-neuropathy (SMON) after an Automated Telephone Call Service

Yasuyuki Ohta, Nozomi Hishikawa, Kota Sato, Mami Takemoto, Tom Yamashita, Shinji Doutare, Koji Abe

INTERNAL MEDICINE 58 ( 8 ) 1081 - 1085 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective We evaluated the clinical effects of a telephone call service for psychological symptoms such as anxiety, depression or apathy in subacute myelo-optico-neuropathy (SMON) patients living alone or with a single caregiver.Methods Up to 16 SMON patients (4 men, 12 women) and 32 control subjects were evaluated by the geriatric depression scale (GDS), apathy scale (AS) and state and trait anxiety inventory (STAI) forms X-I, including the P and A values for depression, apathy and state anxiety including disturbed peace of mind and enhanced anxiety, respectively, before (pre) and three months after (post) the telephone call service.Results The SMON patients, especially women, had significantly worse baseline scores in GDS (depression), AS (apathy) and STAI (state anxiety) than control subjects. The automated telephone call service significantly improved the high baseline STAI scores, including the P and A scores (disturbed peace of mind and enhanced anxiety), of SMON patients but not the GDS or AS scores.Conclusion SMON patients, especially women, living alone or with a single caregiver showed higher baseline depression, apathy and anxiety scores than the control subjects. The present automated telephone call service proved to be a useful care tool for improving the anxiety of SMON patients with high STAI P and A scores.

DOI： 10.2169/internalmedicine.1554-18

Asymmetrical and Isolated Hypoglossal Nerve Palsy Accompanied by a New Subset of Anti-ganglioside Antibodies in a Patient with Diffuse Large B Cell Lymphoma

Yasuyuki Ohta, Yuko Kawahara, Koh Tadokoro, Kota Sato, Ryo Sasaki, Yoshiaki Takahashi, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Takeru Asano, Tomoko Inomata, Koji Abe

INTERNAL MEDICINE 58 ( 2 ) 283 - 286 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Malignant lymphoma sometimes involves peripheral nerves due to paraneoplastic syndrome associated with anti-ganglioside antibodies. We report a very rare case of malignant lymphoma accompanied by an asymmetrical and isolated hypoglossal nerve palsy associated with a new subset of anti-ganglioside antibodies. Magnetic resonance imaging and F-18-2-deoxy-2-fluoro-D-glucose position emission tomography showed no abnormalities of the hypoglossal nerve nucleus; however, the patient's serum was positive for anti-sulfated glucuronyl paragloboside IgM antibodies as well as anti-GM1 IgM and anti-GQ1b IgM antibodies. The present case might suggest a paraneoplastic asymmetrical and isolated hypoglossal nerve palsy associated with a new subset of anti-ganglioside antibodies.

DOI： 10.2169/internalmedicine.1269-18

A Rare Case of Klinefelter Syndrome Accompanied by Spastic Paraplegia and Peripheral Neuropathy

Ryo Sasaki, Yasuyuki Ohta, Yoshiaki Takahashi, Keiichiro Tsunoda, Koh Tadokoro, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Tom Yamashita, Koji Abe

INTERNAL MEDICINE 58 ( 3 ) 437 - 440 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Klinefelter syndrome is a chromosomal disorder with a typical karyotype of 47, XXY, accompanied by various neurological symptoms. We herein report the first case of Klinefelter syndrome with a rare mosaic form of 47, XXY and 48, XXXY, combined with both spastic paraplegia and peripheral motor neuropathy. This case showed spasticity and hyperreflexia with pathological reflexes and ankle clonus as well as muscle weakness in all extremities. A motor nerve conduction study and the magnetic motor evoked potential suggested motor axonal neuropathy and corticospinal tract disorders. The present case suggests that Klinefelter syndrome can present with both upper and lower motor neuron degeneration.

DOI： 10.2169/internalmedicine.1048-18

Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study

Koh Tadokoro, Ryuta Morihara, Yasuyuki Ohta, Nozomi Hishikawa, Satoko Kawano, Ryo Sasaki, Namiko Matsumoto, Emi Nomura, Yumiko Nakano, Yoshiaki Takahashi, Mami Takemoto, Toru Yamashita, Setsuko Ueno, Yosuke Wakutani, Yoshiki Takao, Nobutoshi Morimoto, Yumiko Kutoku, Yoshihide Sunada, Katsushi Taomoto, Yasuhiro Manabe, Kentaro Deguchi, Yasuto Higashi, Haruhiko Inufusa, Fukka You, Toshikazu Yoshikawa, Markus Matuschka von Greiffenclau, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 71 ( 3 ) 1063 - 1069 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n= 37) and TwX (n= 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.

DOI： 10.3233/JAD-190644

Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer's Disease Model

Xiaowen Shi, Yasuyuki Ohta, Xia Liu, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Tian Feng, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toni Yamashita, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 68 ( 4 ) 1667 - 1675 2019

Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

Alzheimer's disease (AD) is the most common dementia and a progressive neurodegenerative disorder aggravated by chronic hypoperfusion (HP). Since numerous evidence suggests that inflammation is related with AD pathology, we investigated the expression change of two anti-inflammatory markers, inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and alpha-2-HS-glycoprotein (AHSG), in a novel AD model (APP23) with HP at 12 month of age. As compared with wild type (WT, n = 10), immunohistochemical analysis showed a higher ITIH4 and a lower AHSG expressions in the cerebral cortex, hippocampus, and thalamus of the APP23 + HP group (n = 12) than the simple APP23 (n =10) group (*p < 0.05 and **p < 0.01 versus WT; (#)p < 0.05 and (##)p < 0.01 versus APP23). The present study provides an upregulation of anti-inflammatory ITIH4 and a downregulation of pro-inflammatory TNF alpha-dependent AHSG in a novel AD plus HP mice model.

DOI： 10.3233/JAD-181218

一般住民健診における不眠症と認知・情動機能障害の特徴

菱川望, 福井裕介, 武本麻美, 商敬偉, 佐藤恒太, 太田康之, 山下徹, 阿部康二

臨床神経学 58 ( Suppl. ) S299 - S299 2018.12

Neuroprotective effects of SMTP-44D in mice stroke model in relation to neurovascular unit and trophic coupling

Xiaowen Shi, Yasuyuki Ohta, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xia Liu, Tian Feng, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Eriko Suzuki, Keiji Hasumi, Koji Abe

JOURNAL OF NEUROSCIENCE RESEARCH 96 ( 12 ) 1887 - 1899 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Stachybotrys microspora triprenyl phenol (SMTP)-44D has both anti-oxidative and anti-inflammatory activities, but its efficacy has not been proved in relation to the pathological changes of neurovascular unit (NVU) and neurovascular trophic coupling (NVTC) in ischemic stroke. Here, the present study was designed to assess the efficacies of SMTP-44D, moreover, compared with the standard neuroprotective reagent edaravone in ischemic brains. ICR mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min, SMTP-44D (10 mg/kg) or edaravone (3 mg/kg) was intravenously administrated through subclavian vein just after the reperfusion, and these mice were examined at 1, 3, and 7 d after reperfusion. Compared with the vehicle group, SMTP-44D treatment revealed obvious ameliorations in clinical scores and infarct volume, meanwhile, markedly suppressed the accumulations of 4-HNE, 8-OHdG, nitrotyrosine, RAGE, TNF-alpha, Iba-1, and cleaved caspase-3 after tMCAO. In addition, SMTP-44D significantly prevented the dissociation of NVU and improved the intensity of NAGO/BDNF and the number of BDNF/TrkB and BDNF/NeuN double positive cells. These effects of SMTP-44D in reducing oxidative and inflammatory stresses were similar to or stronger than those of edaravone. The present study demonstrated that SMTP-44D showed strong anti-oxidative, anti-inflammatory, and anti-apoptotic effects, moreover, the drug also significantly improved the NVU damage and NVTC in the ischemic brain.

DOI： 10.1002/jnr.24326

Different clinicopathological features between Japanese siblings with facioscapulohumeral muscular dystrophy 2 with a novel nonsense SMCHD1 mutation (Arg552*)

Yasuyuki Ohta, Koh Tadokoro, Ryo Sasaki, Yoshiaki Takahashi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Jingwei Shang, Toru Yamashita, Yasushi Takehisa, Ichizo Nishino, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 58 215 - 217 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Facioscapulohumeral muscular dystrophy (FSHD) 2 is caused by a combination of heterozygous structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHDI) mutation plus DNA hypomethylation on D4Z4. Here we report two Japanese FSHD2 siblings (brother and sister) with a new SMCHD1 nonsense mutation (a heterogeneous c. 1654C > T substitution, leading to a stop codon Arg552*). They showed the typical phenotype of FSHD2 such as asymmetric muscle weakness and atrophy in bilateral facial, scapular and humeral muscles, but different clinicopathological features between them. The brother and asymptomatic mother showed normal D4Z4 methylation plus the same SMCHD1 mutation, but the sister showed the SMCHD1 mutation plus D4Z4 hypomethylation, suggesting an interesting correlation of the new SMCHD1 nonsense mutation and D4Z4 hypomethylation. (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2018.10.021

Cervical compressive myelopathy caused by malfunction of a programmable cerebrospinal fluid shunt valve Reviewed

Kota Sato, Toru Yamashita, Keichiro Tsunoda, Mami Takemoto, Nozomi Hishikawa, Jinwei Shang, Yasuyuki Ohta, Ken Kuwahara, Takao Yasuhara, Isao Date, Koji Abe

INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT 14 183 - 185 2018.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

The primary treatment for hydrocephalus is ventricular shunt placement, and a programmable valve is widely used for ventriculoperitoneal (VP) shunt surgery to reduce over/under drainage of cerebrospinal fluid (CSF). Here, we report a rare case of a patient who developed successive VP shunt malfunction causing spastic muscle weakness in extremities associated cervical epidural venous distension and compressive myelopathy due to over-drainage of CSF through a defective VP shunt valve a decade after the initial shunt was placed. One should be aware and cognizant of this complication and carefully follow the symptoms and potentially utilize brain MRI with and without contrast to look at over drainage stigmata to avoid the development of neurological complications.

DOI： 10.1016/j.inat.2018.08.009

Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects

Yong Huang, Yasuyuki Ohta, Jingwei Shang, Xianghong Li, Xia Liu, Xiaowen Shi, Tian Feng, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Eriko Suzuki, Keiji Hasumi, Koji Abe

Journal of Stroke and Cerebrovascular Diseases 27 ( 12 ) 3521 - 3528 2018.12

Publishing type：Research paper (scientific journal)

© 2018 Background: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice. Methods: After 60 minutes tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains. Results: SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect. Conclusions: The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.08.018

Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects

Yong Huang, Yasuyuki Ohta, Jingwei Shang, Xianghong Li, Xia Liu, Xiaowen Shi, Tian Feng, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Eriko Suzuki, Keiji Hasumi, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 27 ( 12 ) 3521 - 3528 2018.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice. Methods: After 60 minutes tMCAO, 0.9% NaC1, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains. Results: SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect. Conclusions: The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.08.018

コリンエステラーゼ阻害剤変更によるアルツハイマー病患者への影響

太田康之, 菱川望, 山下徹, 佐藤恒太, 武本麻美, 阿部康二

神経治療学 35 ( 6 ) S238 - S238 2018.11

A case of aspergillotic orbital apex syndrome diagnosed by an additional intraorbital biopsy after nasal endoscopy Reviewed

Namiko Matsumoto, Kota Sato, Koh Tadokoro, Yoshiaki Takahashi, Taijun Yunoki, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Kentaro Fujii, Tomotsugu Ichikawa, Isao Date, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 6 ) 188 - 190 2018.11

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The prompt and accurate diagnosis of orbital apex syndrome (OAS) is very important because of its fatality. Here we report an old man with aspergillotic OAS diagnosed after two biopsies by nasal endoscopy and craniotomy. Only craniotomy leads to the appropriate diagnosis, suggesting an immediate need of additional biopsy for the accurate diagnosis and saving the patient.

DOI： 10.1111/ncn3.12226

Antineuroinflammatory Effect of SMTP-7 in Ischemic Mice

Yong Huang, Yasuyuki Ohta, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xia Liu, Xiaowen Shi, Tian Feng, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Eriko Suzuki, Keiji Hasumi, Koji Abe

Journal of Stroke and Cerebrovascular Diseases 27 ( 11 ) 3084 - 3094 2018.11

Publishing type：Research paper (scientific journal)

© 2018 Background: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both potentials of thrombolytic and neuroprotective effects, but its detailed neuroprotective mechanisms in ischemic stroke are still unclear. Here, we assessed the neuroprotective effects of SMTP-7 for anti-inflammatory and antiapoptosis mechanisms after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice. Methods: After 60 minutes of tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA+SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the antineuroinflammatory effect of SMTP-7 on the expressive changes of inflammatory markers in ischemic mouse brains. Results: Compared with the vehicle and tPA groups, SMTP-7 treatment significantly improved clinical scores and decreased the infarct volume and the numbers of TNF-α, nuclear factor-κB (NF-κB), nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and cleaved caspase-3-positive cells in the brain of mice at 24 hours after tMCAO but not p62-positive cells. However, tPA+SMTP-7 treatment did not show such effects. Conclusions: The present study suggested that SMTP-7 provides a therapeutic benefit for ischemic stroke mice through anti-inflammatory and antiapoptotic effects but not antiautophagic effect.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.06.039

Antineuroinflammatory Effect of SMTP-7 in Ischemic Mice

Yong Huang, Yasuyuki Ohta, Jingwei Shang, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xia Liu, Xiaowen Shi, Tian Feng, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Eriko Suzuki, Keiji Hasumi, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 27 ( 11 ) 3084 - 3094 2018.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background: Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both potentials of thrombolytic and neuroprotective effects, but its detailed neuroprotective mechanisms in ischemic stroke are still unclear. Here, we assessed the neuroprotective effects of SMTP-7 for anti-inflammatory and antiapoptosis mechanisms after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice. Methods: After 60 minutes of tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA+SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the antineuroinflammatory effect of SMTP-7 on the expressive changes of inflammatory markers in ischemic mouse brains. Results: Compared with the vehicle and tPA groups, SMTP-7 treatment significantly improved clinical scores and decreased the infarct volume and the numbers of TNE-alpha, nuclear factor-kappa B (NF-kappa B), nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and cleaved caspase-3-positive cells in the brain of mice at 24 hours after tMCAO but not p62-positive cells. However, tPA+SMTP-7 treatment did not show such effects. Conclusions: The present study suggested that SMTP-7 provides a therapeutic benefit for ischemic stroke mice through anti-inflammatory and antiapoptotic effects but not antiautophagic effect.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.06.039

胃瘻造設後に高浸透圧高血糖症候群をきたした進行性核上性麻痺の一例

田所功, 佐藤恒太, 森原隆太, 佐々木諒, 高橋義秋, 商敬偉, 武本麻美, 菱川望, 太田康之, 山下徹, 阿部康二

日本難病医療ネットワーク学会機関誌 6 ( 1 ) 81 - 81 2018.11

マウス脳梗塞モデルにおける新規抗酸化サプリメントTwendeeXの脳保護効果

中野由美子, 草木桃子, 太田康之, 山下徹, 犬房春彦, 森原隆太, 商敬偉, 佐藤恒太, 武本麻美, 菱川望, 阿部康二

脳循環代謝 30 ( 1 ) 140 - 140 2018.10

Affective improvement of neurological disease patients and caregivers using an automated telephone call service

Yasuyuki Ohta, Toru Yamashita, Nozomi Hishikawa, Kota Sato, Noriko Hatanaka, Mami Takemoto, Shinji Doutare, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 56 74 - 78 2018.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Neurological disease patients living alone or with a single caregiver need a support system to care for their psychological symptoms. We evaluated the clinical effects of a unique telephone call system that automatically called participants at their desired times once a week for 3 months. In total, 104 neurological disease patients and caregivers were evaluated by the geriatric depression scale, apathy scale and state and trait anxiety inventories (STAI) forms X-I for depression, apathy and state anxiety, respectively. High baseline STAI scores (40 >=) significantly improved in the Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and spinocerebellar degeneration (SCD) + multiple system atrophy (MSA) patients (p = 0.001, p = 0.013 and p = 0.046, respectively) after patients/caregivers used the telephone call service. The baseline (pre) STAI score significantly correlated with the score change (post-pre) in PD, ALS, SCD + MSA, Alzheimer' s disease patients (ADp), and caregivers for ADp (p < 0.0001, p = 0.001, p = 0.011, p = 0.025 and p = 0.020, respectively). The geriatric depression scale and apathy scale did not significantly improve. The present study suggests that there is a positive effect of using an automated telephone call service for anxiety in neurological disease patients and caregivers, especially in ALS, SCD + MSA and PD patients with high STAI scores (40 >=). (C) 2018 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2018.07.006

コリンエステラーゼ阻害剤変更によるアルツハイマー病患者への治療効果

太田康之, 菱川望, 山下徹, 佐藤恒太, 武本麻美, 阿部康二

Dementia Japan 32 ( 3 ) 473 - 473 2018.9

Rare valiant vertical one-and-a-half syndrome without ipsilateral upward gaze palsy in a patient with thalamomesencephalic stroke

Kota Sato, Yoshiaki Takahashi, Namiko Matsumoto, Taijun Yunoki, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 5 ) 133 - 135 2018.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Bilateral upward and ipsilateral downward gaze palsy due to a unilateral thalamomesencephalic stroke is called vertical one-and-a-half syndrome (VOHS). Here, we report a valiant VOHS case who presented contralateral upward and ipsilateral downward gaze palsy due to a unilateral thalamomesencephalic stroke. The neuronal fiber connections associated with vertical gaze are not completely understood, so the present case provides an important proof to obtain a better understanding of vertical gaze mechanisms.

DOI： 10.1111/ncn3.12210

Vogt-Koyanagi-Harada case accompanied by polyneuropathy Reviewed

Keiichiro Tsunoda, Yasuyuki Ohta, Koh Tadokoro, Ryo Sasaki, Yoshiaki Takahashi, Kota Sato, Emi Nomura, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Ai Kajita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 5 ) 138 - 140 2018.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Vogt-Koyanagi-Harada disease (VKHD) is a systemic autoimmune disease that targets melanocyte-rich tissues such as eye, central nervous system, inner ear, and skin. Here, we report a case of VKHD accompanied by polyneuropathy. After VKHD was diagnosed, depending on the involvement of bilateral ocular, auditory, and central nervous systems, he expressed muscle weakness, pain, and numbness in bilateral lower extremities. Nerve conduction studies suggested sensorimotor polyneuropathy, while a skin, muscle, and nerve biopsy suggested vasculitis. Steroid therapy improved his symptoms. The present case might suggest a relationship between VKHD and polyneuropathy.

DOI： 10.1111/ncn3.12213

Therapeutic Effects of Pretreatment with Tocovid on Oxidative Stress in Postischemic Mice Brain

Jingwei Shang, Hongjing Yan, Yang Jiao, Yasuyuki Ohta, Xia Liu, Xianghong Li, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xiaowen Shi, Yong Huang, Tian Feng, Mami Takemoto, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 27 ( 8 ) 2096 - 2105 2018.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. Materials and Methods: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. Results: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expreisions after tMCAO. Conclusions: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.03.012

Detecting spinal spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography

Yusuke Fukui, Nozomi Hishikawa, Kota Sato, Yumiko Nakano, Ryuta Morihara, Jingwei Shang, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROSCIENCE RESEARCH 133 58 - 63 2018.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

The objective of this study was to determine alteration of corticospinal tract in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal controls, and then ALS were divided into two subgroups according to their clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5. The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were significantly reduced compared with normal controls, and SBMA patients. On the other hand, the mean diffusivity (MD) values were not significantly different among normal controls and the three disease groups. The rate of disease progression (Delta FRS-R) of ALS patients was significantly correlated with FA values and central motor conduction time (CMCT). In conclusion, the present study demonstrated a significant reduction of FA values in ALS patients, and the Delta FRS-R of ALS patients showed distinct regressions with FA values and CMCT, suggesting that this DTT analysis could be useful for detecting disease progression of ALS patients. (C) 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2017.11.005

Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography Reviewed

Yusuke Fukui, Nozomi Hishikawa, Kota Sato, Yumiko Nakano, Ryuta Morihara, Jingwei Shang, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

Neuroscience Research 133 58 - 63 2018.8

Language：English Publishing type：Research paper (scientific journal)

© 2017 Elsevier Ireland Ltd and Japan Neuroscience Society The objective of this study was to determine alteration of corticospinal tract in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal controls, and then ALS were divided into two subgroups according to their clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5. The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were significantly reduced compared with normal controls, and SBMA patients. On the other hand, the mean diffusivity (MD) values were not significantly different among normal controls and the three disease groups. The rate of disease progression (ΔFRS-R) of ALS patients was significantly correlated with FA values and central motor conduction time (CMCT). In conclusion, the present study demonstrated a significant reduction of FA values in ALS patients, and the ΔFRS-R of ALS patients showed distinct regressions with FA values and CMCT, suggesting that this DTT analysis could be useful for detecting disease progression of ALS patients.

DOI： 10.1016/j.neures.2017.11.005

Neuroprotective Effects of Tocovid Pretreatment in a Mouse Stroke Model

Yang Jiao, Jingwei Shang, Yasuyuki Ohta, Hongjing Yan, Xia Liu, Xianghong Li, Ryuta Morihara, Yumiko Nakano, Yusuke Fukui, Xiaowen Shi, Yong Huang, Tian Feng, Mami Takemoto, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 27 ( 8 ) 2166 - 2174 2018.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background: Tocovid is a new combination of tocotrienols and tocopherol, both of which are neuroprotective agents for preventing cerebral infarction in mice. However, the effects of tocovid on anti-inflammation in ischemic model remain elusive. In the present study, we assessed the effects of Tocovid pretreatment on anti-inflammatory effects after transient middle cerebral occlusion (tMCAO) in mice. Materials and Methods: We evaluated the therapeutic and anti-inflammatory effects of tocovid pretreatment (200 mg/kg per day, for 1 month) on mice brain under 60 minutes of tMCAO. The expressive changes of inflammatory markers were ob-served after tMCAO in mice. Results: Tocovid pretreatment greatly improved the mice neurobehaviors, reduced infarct volumes and decreased expressions of in-flammatory markers such as tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1) and ionized calcium binding adapter molecule-1 (Iba-1), and improved the damage of neurovascular units including matrix metallopeptidase 9, IgG and collagen IV after tMCAO. Conclusions: Our present findings demon-strated that oral tocovid pretreatment showed obviously neuroprotective and at least in part by anti-inflammatory effects in ischemic mice brain.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.03.014

A unique telephone support system for dementia patients and their caregivers managed in Japan (Okayama Dementia Call Center, ODCC) Reviewed

Yumiko Nakano, Nozomi Hishikawa, Keiko Sakamoto, Yoko Myoraku, Yoshinori Ozaki, Mami Takemoto, Kota Sato, Toru Yamashita, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 4 ) 100 - 103 2018.7

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Background: Despite a rapidly increasing prevalence of dementia, social support systems for dementia patients and their caregivers are insufficient.Aim: To investigate a telephone support system for dementia patients and their caregivers managed by a local public association, the Okayama Dementia Call Center (ODCC).Methods: A total of 1485 phone calls were retrospectively surveyed over 4 years (from June 2011 to May 2014) and were divided into four annual periods.Results: The average consulting time of each of the 1485 phone calls was 20.2 14.7 min. The chief complaint was distress related to dementia symptoms (56.2%), mainly from the children (66.7%) and spouses (17.5%) of dementia patients. With respect to management of ODCC for these clients, the proportion of providing advice has decreased (66.1 to 47.7%) as that of listening time increased (22.7 to 46.1%).Conclusion: The present unique telephone call system (ODCC) may supplement an insufficient social support, and may play an important role in the community care system, enabling people with dementia to live comfortably in their local community.

DOI： 10.1111/ncn3.12200

Fulminant Guillain-Barre syndrome with Takotsubo cardiomyopathy: Report of an autopsied case Reviewed

Mami Takemoto, Toru Yamashita, Yasuyuki Ohta, Nozomi Hishikawa, Kota Sato, Keiichiro Tsunoda, Jingwei Shang, Kentaro Deguchi, Takehiro Tanaka, Hirotake Nishimura, Masumi Furutani, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 4 ) 117 - 119 2018.7

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report a case of a 77-year-old Japanese man with a fever of up to 39.0 degrees C, which subsided after 5 days. The patient showed fulminant Guillain-Barre syndrome (GBS), severe autonomic dysfunction with a labile blood pressure, an unstable heart rate from onset to death, and Takotsubo cardiomyopathy. Although Takotsubo cardiomyopathy was ameliorated by Day 14 (from admission in the hospital) with a normalized electrocardiogram, his blood pressure became markedly more variable and he died on Day 26. In the present report, we describe an autopsied case of GBS with Takotsubo cardiomyopathy.

DOI： 10.1111/ncn3.12197

Clinical predictors of Alzheimer's disease progression

Nozomi Hishikawa, Yusuke Fukui, Mami Takemoto, Kota Sato, Jingwei Shang, Toru Yamashita, Yasuyuki Ohta, Koji Abe

GERIATRICS & GERONTOLOGY INTERNATIONAL 18 ( 6 ) 929 - 936 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

AimRates of disease progression differ among patients with Alzheimer's disease (AD), but prognostic predictions remain a challenge. We carried out a clinic-based retrospective study to investigate the clinical factors for AD progression.MethodsThe 748AD patients, who attended our hospital for >1year and were given the Mini-Mental State Examination (MMSE) at least three times, were divided into three groups according to the annual change rate of MMSE score (G): Aggravater group (G<-2), Stabler group (-2G2) and Improver group (2<G). We compared the three groups on cognitive, affective and activities of daily living functions, response to medication, clinical fluctuations, serum levels of metabolic factors, and neuroimaging data.ResultsWe found no significant differences in age, sex, educational attainment or body mass index across the groups. The Aggravater group showed better baseline MMSE (P<0.01) and Abe's behavioral and psychological symptoms of dementia (P<0.01) scores than the Improver group, but its MMSE improvement after drug treatment was the worst among the three groups (P<0.01 vs Stabler/Improver). Fluctuations in MMSE (P<0.01), apathy scale (P<0.05) and activities of daily living (P<0.01) scores were smaller in the Improver group than in the Aggravater or Stabler groups. Serum docosahexaenoic acid levels tended to be lower (trend P<0.05) and voxel-based specific regional analysis system for Alzheimer's disease Z-scores tended to be higher (trend P<0.05) in the Improver group than in the Stabler or Aggravater groups.ConclusionsInitial responses to medication, fluctuations in cognitive, affective and activities of daily living functions, serum docosahexaenoic acid levels, and medial temporal atrophy are clinical factors related to AD prognosis. Geriatr Gerontol Int 2018; 18: 929-936.

DOI： 10.1111/ggi.13286

Clinical predictors of Alzheimer's disease progression

Nozomi Hishikawa, Yusuke Fukui, Mami Takemoto, Kota Sato, Jingwei Shang, Toru Yamashita, Yasuyuki Ohta, Koji Abe

Geriatrics and Gerontology International 18 ( 6 ) 929 - 936 2018.6

Publishing type：Research paper (scientific journal)

© 2018 Japan Geriatrics Society Aim: Rates of disease progression differ among patients with Alzheimer's disease (AD), but prognostic predictions remain a challenge. We carried out a clinic-based retrospective study to investigate the clinical factors for AD progression. Methods: The 748 AD patients, who attended our hospital for >1 year and were given the Mini-Mental State Examination (MMSE) at least three times, were divided into three groups according to the annual change rate of MMSE score (G): Aggravater group (G < −2), Stabler group (−2 ≤ G ≤ 2) and Improver group (2 < G). We compared the three groups on cognitive, affective and activities of daily living functions, response to medication, clinical fluctuations, serum levels of metabolic factors, and neuroimaging data. Results: We found no significant differences in age, sex, educational attainment or body mass index across the groups. The Aggravater group showed better baseline MMSE (P < 0.01) and Abe's behavioral and psychological symptoms of dementia (P < 0.01) scores than the Improver group, but its MMSE improvement after drug treatment was the worst among the three groups (P < 0.01 vs Stabler/Improver). Fluctuations in MMSE (P < 0.01), apathy scale (P < 0.05) and activities of daily living (P < 0.01) scores were smaller in the Improver group than in the Aggravater or Stabler groups. Serum docosahexaenoic acid levels tended to be lower (trend P < 0.05) and voxel-based specific regional analysis system for Alzheimer's disease Z-scores tended to be higher (trend P < 0.05) in the Improver group than in the Stabler or Aggravater groups. Conclusions: Initial responses to medication, fluctuations in cognitive, affective and activities of daily living functions, serum docosahexaenoic acid levels, and medial temporal atrophy are clinical factors related to AD prognosis. Geriatr Gerontol Int 2018; 18: 929–936.

DOI： 10.1111/ggi.13286

A case of bilateral internal carotid artery dissection in young adult with cranial nerve IX and X palsies Reviewed

Ryo Sasaki, Toru Yamashita, Yoshiaki Takahashi, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 3 ) 80 - 82 2018.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Internal carotid artery (ICA) dissection is a major cause of cerebral infarction in young adult and usually presents cervical pain and headache, but rarely presents cranial nerve palsy. Here, we report a case of rare bilateral ICA dissections in young adult with cranial nerve IX and X palsies as initial symptom. He presented dysarthria and nasal voice at an early stage, followed by a small brain infarction. The cranial nerve palsy was improved in parallel with the improvement of ICA stenosis and dilatation. It is important to know that cranial nerve palsy can be one of the symptoms of ICA dissection for appropriate treatment.

DOI： 10.1111/ncn3.12187

Case of acromegalic myopathy and arthropathy long after trans-sphenoidal surgery Reviewed

Ryo Sasaki, Toru Yamashita, Yoshiaki Takahashi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 3 ) 77 - 79 2018.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Acromegaly patients usually show impaired vision, the enlargement of hands and feet, heart failure, and diabetes and rarely show myopathy (weakness and muscle pain) and arthropathy (joint pain). Here, we report an acromegaly patient who showed progressive myopathy and arthropathy long after a Hardy operation. The symptoms of myopathy and arthropathy occurred under normal GH and high IGF-1 levels, but these symptoms improved when the IGF-1 level was normalized by a treatment of octreotide with an increased dose of 30-40 mg. Thus, strict and immediate control of IGH-1 may be pivotally important to prevent and treat acromegalic myopathy and arthropathy.

DOI： 10.1111/ncn3.12191

Case of congenital fibrosis of the extraocular muscles type 1 with progressive cerebellar ataxia

Toru Yamashita, Yoshiaki Takahashi, Keiichiro Tsunoda, Emi Nomura, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 2 ) 48 - 50 2018.3

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

A 70-year-old women presented classical CEFOM1 phenotypes such as bilateral ptosis and external ophthalmoplegia, but also progressive cerebellar ataxia, carrying a previously reported heterozygous missense mutation of KIF21A p.Arg941Gln. The present case is the first report of CFEOM1 showing cerebellar atrophy with hypoperfusion, mainly of the vermis, indicating that cerebellar function should be carefully evaluated in CFFOM1 patients.

DOI： 10.1111/ncn3.12178

Emergency ventricular drainage plus systemic antibiotics saved an elderly patient with intraventricular rupture as a result of a pituitary abscess

Yoshiaki Takahashi, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 6 ( 1 ) 13 - 15 2018.1

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

A pituitary abscess is a rare intracranial infection, and direct transsphenoidal surgery is common for the therapy. Intracranial rupture of the pituitary abscess is usually fatal. Here, we report a 76-year-old woman with a pituitary abscess who showed headaches, left eyelid ptosis, periorbital swelling and external eye movement disturbances in the left eye. Although her symptoms initially improved after therapy with systemic antibiotics, the pituitary abscess suddenly developed an intraventricular rupture on admission day 27. However, emergency ventricular drainage in combination with different antibiotics gradually improved her condition. The present case suggests that the combination of emergency ventricular drainage and systemic antibiotic administration could serve as an alternative choice to manage pituitary abscesses of ventricular ruptures, especially in elderly patients.

DOI： 10.1111/ncn3.12167

A Japanese Encephalitis Patient Presenting with Parkinsonism with Corresponding Laterality of Magnetic Resonance and Dopamine Transporter Imaging Findings

Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Takahiro Maeki, Ryo Sasaki, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Chang Kweng Lim, Shigeru Tajima, Koji Abe

INTERNAL MEDICINE 57 ( 15 ) 2243 - 2246 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using I-123-labeled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (I-123-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE.

DOI： 10.2169/internalmedicine.0337-17

Neurolymphomatosis in the Cauda Equina Diagnosed by an Open Biopsy

Ryo Sasaki, Yasuyuki Ohta, Yuto Yamada, Koh Tadokoro, Yoshiaki Takahashi, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Takao Yasuhara, Isao Date, Shuntaro Ikegawa, Nobuharu Fujii, Koji Abe

INTERNAL MEDICINE 57 ( 23 ) 3463 - 3465 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Neurolymphomatosis is a rare form of extranodal malignant lymphoma defined as the infiltration of malignant lymphocytes into the central or peripheral nerve. We herein report a case of neurolymphomatosis in the cauda equina diagnosed by an open surgical biopsy. He presented with muscle weakness, atrophy, numbness and hypoesthesia in the bilateral lower extremities with the accumulation of (18)fluoro-2-deoxyglucose (FDG) in the bilateral cauda equina. Cerebrospinal fluid cytology (three times) and flow cytometry (two times) and biopsies of the left rural nerve, bone marrow, paranasal sinus and left testis were all negative for malignancy, so finally we performed a surgical open biopsy of the cauda equina by laminectomy and diagnosed him with diffuse large B-cell lymphoma in the cauda equina. He was successfully treated with the disappearance of the FDG accumulation for a long time. The present case suggested that an early open biopsy of the cauda equina may be considered for cases of suspected neurolymphomatosis in the cauda equina for a good outcome.

DOI： 10.2169/internalmedicine.1049-18

A unique case of hemi-tongue pseudohypertrophy, necrotizing myopathy, and erythema nodosum

Kota Sato, Yoshiaki Takahashi, Toni Yamashita, Mami Takemoto, Nozomi Hishikawa, Shang Jinwei, Yasuyuki Ohta, Koji Abe

NEUROLOGY INTERNATIONAL 10 ( 4 ) 95 - 96 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：PAGEPRESS PUBL

A 46-year-old woman developed slowly progressive tongue weakness with a pseudohypertrophic change on the right side of her tongue. She subsequently developed weakness in her proximal lower extremities, skin erythema and a sustained increase of muscle enzymes at 11 M after the onset. A biopsy of the quadriceps muscle showed necrotizing myopathy and a skin biopsy showed erythema nodosum. The present case showed characteristic clinical manifestations that may represent a rare variant of sarcoidosis.

DOI： 10.4081/ni.2018.7852

A Unique Case with Oral Dyskinesia, Chorea, Ataxia, and Mild Cognitive Impairment with Caudate Atrophy and Characteristic Brain Calcifications

Nozomi Flishikawa, Yusuke Fukui, Kota Sato, Mami Takemoto, Tom Yamashita, Yasuyuki Ohta, Koji Abe

INTERNAL MEDICINE 57 ( 16 ) 2399 - 2402 2018

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

The authors report a man who developed oral dyskinesia at 46 years of age, followed by slowly progressive choreic movement and mild cognitive impairment over 20 years. He showed caudate atrophy and four types of intracranial calcification in the hippocampus (dot-like), cerebellar white matter (vague-mass), occipital cortices (laminar), and cerebral white matter (linear). Linear-calcification in the corona radiata seems to be deposition along small veins, which may be related to the white matter changes and to the decreased regional cerebral blood flow in the frontal and parietal lobes. The present case shows a slowly progressive disease with caudate atrophy and characteristic brain calcifications.

DOI： 10.2169/internalmedicine.9454-17

A unique case with oral dyskinesia, chorea, ataxia, and mild cognitive impairment with caudate atrophy and characteristic brain calcifications

Nozomi Hishikawa, Yusuke Fukui, Kota Sato, Mami Takemoto, Toru Yamashita, Yasuyuki Ohta, Koji Abe

Internal Medicine 57 ( 16 ) 2399 - 2402 2018

Language：English Publishing type：Research paper (scientific journal)

© 2018 The Japanese Society of Internal Medicine. The authors report a man who developed oral dyskinesia at 46 years of age, followed by slowly progressive choreic movement and mild cognitive impairment over 20 years. He showed caudate atrophy and four types of intracranial calcification in the hippocampus (dot-like), cerebellar white matter (vague-mass), occipi-tal cortices (laminar), and cerebral white matter (linear). Linear-calcification in the corona radiata seems to be deposition along small veins, which may be related to the white matter changes and to the decreased regional cerebral blood flow in the frontal and parietal lobes. The present case shows a slowly progressive disease with caudate atrophy and characteristic brain calcifications.

DOI： 10.2169/internalmedicine.9454-17

PDDとDLBの認知機能、情動機能、脳血流分布の比較検討

武本麻美, 菱川望, 太田康之, 山下徹, 佐藤恒太, 幡中典子, 阿部康二

Anti-aging Science 9 ( 2 ) 109 - 109 2017.12

メタボリック症候群を伴うアルツハイマー病の特徴

菱川望, 福井裕介, 武本麻美, 佐藤恒太, 太田康之, 山下徹, 阿部康二

Anti-aging Science 9 ( 2 ) 111 - 111 2017.12

大脳白質病変を伴うアルツハイマー病患者における抗認知症薬の臨床的効果

福井裕介, 菱川望, 佐藤恒太, 中野由美子, 森原隆太, 武本麻美, 商敬偉, 太田康之, 山下徹, 阿部康二

Anti-aging Science 9 ( 2 ) 110 - 110 2017.12

A migration case of Kii amyotrophic lateral sclerosis/parkinsonism dementia complex with the shortest stay in the endemic area and the longest incubation to develop the disease Reviewed

Keiichiro Tsunoda, Toru Yamashita, Hitoshi Shimada, Emi Nomura, Yoshiaki Takahashi, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Makoto Higuchi, Tetsuya Suhara, Yasumasa Kokubo, Shigeki Kuzuhara, Koji Abe

JOURNAL OF CLINICAL NEUROSCIENCE 46 64 - 67 2017.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) is an endemic disease observed in the Kii peninsula, Guam, and Papua. We report a case of a 76-year old man with ALS/PDC of the Kii peninsula of Japan (Kii ALS/PDC). The patient was born and grew up in the Kii peninsula. He moved out at age three, and developed symptoms 73 years later. He showed pyramidal sign, parkinsonian symptoms, and mildly impaired cognitive function. I-131-metaiodobenzylguanidine myocardial scintigraphy showed decreased cardiac sympathetic nerve function, and dopamine transporter single photon emission computed tomography imaging showed decreased I-123-N-omega-fluoropropy1-2 beta-carbomethoxy3 beta-(4-iodo phenyl) nortropane accumulation. Cerebral blood flow showed hypoperfusion. Positron emission tomography showed widespread tau deposition in his brain. This is a migration case of Kii ALS/PDC with the shortest stay in the endemic area and the longest delay to develop the disease, indicating a genetic factor for the disease development in a considerable degree. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jocn.2017.08.057

Serious hyponatremia induced by a combination of angiotensin II receptor blocker and thiazide caused deterioration of cognitive functions and psychological symptoms in an elderly Alzheimer's disease patient

Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toru Yamashita, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 6 ) 192 - 194 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

As the number of elderly people increases, Alzheimer's disease and hypertension have become more common. This is an important case report that shows severe hyponatremia induced by a combination of angiotensin II receptor blocker and thiazide, causing the deterioration of cognitive functions in an elderly patient. In rapidly aging societies around the world, more attention should be paid to hyponatremia under combination therapy of angiotensin II receptor blocker plus thiazide to assist elderly patients.

DOI： 10.1111/ncn3.12161

Japanese sibling cases of multiple sclerosis presenting with different clinical phenotypes

Kota Sato, Yasuyuki Ohta, Toru Yamashita, Keiichiro Tsunoda, Kentaro Deguchi, Mami Takemoto, Nozomi Hishikawa, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 6 ) 186 - 188 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Unlike in Western countries, only a few familial multiple sclerosis cases have been reported from Asian countries. Herein, we report on the characteristics of siblings with multiple sclerosis. Their parents were consanguineous, and the siblings showed different first symptoms of gait disturbance or double vision, with a clinical phenotype of primary progressive multiple sclerosis or relapse-remitting multiple sclerosis. Their human leukocyte antigen showed unique subtypes of DPB1 (0501/0901 or 0901/0901) and DRB1 (0406/1502 or 1502/1502).

DOI： 10.1111/ncn3.12145

Type 2 Alexander disease with a novel glial fibrillary acidic protein gene mutation and its unique clinical features

Yuko Kawahara, Toru Yamashita, Yasuyuki Ohta, Kota Sato, Emi Nomura, Mami Takemoto, Nozomi Hishikawa, Jingwei Shang, Tomokatsu Yoshida, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 6 ) 183 - 185 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

We report mother-daughter cases of type 2 Alexander disease with a novel glial fibrillary acidic protein gene mutation. The mother (proband) began to show slowly progressive gait disturbance. However, after an incidental medical checkup, it took just 9 months for the diagnosis. Different from the previous reports, she showed a unique phenotype in points of scoliosis without palatal myoclonus, decreased regional cerebral blood flow in the frontal lobe and mild cognitive impairment. Her second daughter showed mild intellectual disability. Genetic analysis of the mother and the second daughter showed the same novel glial fibrillary acidic protein gene mutation (c.371_372insAGA).

DOI： 10.1111/ncn3.12146

Therapeutic effects of drug switching between acetylcholinesterase inhibitors in patients with Alzheimer's disease. Reviewed

Yasuyuki Ohta, Mohamed Darwish, Nozomi Hishikawa, Toru Yamashita, Kota Sato, Mami Takemoto, Koji Abe

Geriatrics & gerontology international 17 ( 11 ) 1843 - 1848 2017.11

Language：English Publishing type：Research paper (scientific journal)

AIM: To evaluate the therapeutic effects of switching from one acetylcholinesterase inhibitor (ChEI), donepezil, galantamine or rivastigmine, to another in Alzheimer's disease patients. METHODS: We retrospectively enrolled 171 Alzheimer's disease patients, whose ChEI medication was changed. The patients were evaluated on three major aspects of dementia - cognitive, affective and activities of daily living (ADL) measures - at 6 months (M) before the drug switch, at the time of drug switch (baseline), and at 3 M and 6 M after the drug switch. RESULTS: The doses of the three ChEI were significantly lower at 6 M after the switch compared with the pre-switch doses. Improvements in apathy were found at 3 M when switching from donepezil to galantamine, but not to rivastigmine, but this switch had adverse effects on ADL. Improvements in cognitive scores at 3 M were also found when switching from galantamine to rivastigmine, but not to donepezil. However, both of these changes improved Abe's Behavioral and Psychological Symptoms of Dementia scores (ABS), except ADL. Switching from rivastigmine to donepezil worsened ABS at 6 M, but preserved cognitive and ADL scores. CONCLUSIONS: The present study suggests that despite a relatively lower dose of ChEI after the switch, switching from donepezil or rivastigmine preserved cognitive functions for at least 6 M. Switching from galantamine to rivastigmine improved Mini-Mental State Examination and ABS at 3 M, but did not improve ADL scores. Geriatr Gerontol Int 2017; 17: 1843-1848.

DOI： 10.1111/ggi.12971

緊急脳室ドレナージと全身抗生剤で救命しえた下垂体部膿瘍から脳室穿破を来した一例

高橋義秋, 山下徹, 森原隆太, 中野由美子, 商敬偉, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

日本頭痛学会誌 44 ( 2 ) 386 - 386 2017.11

拍動性頭痛を伴う繰り返すTIA症状で再発性の内頸動脈攣縮が疑われた一例

中野由美子, 佐藤恒太, 高橋義秋, 武本麻美, 菱川望, 山下徹, 太田康之, 阿部康二

日本頭痛学会誌 44 ( 2 ) 374 - 374 2017.11

緊急脳室ドレナージと全身抗生剤で救命しえた下垂体部膿瘍から脳室穿破を来した一例

高橋義秋, 山下徹, 森原隆太, 中野由美子, 商敬偉, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

日本頭痛学会誌 44 ( 2 ) 386 - 386 2017.11

緊急脳室ドレナージと全身抗生剤投与にて救命しえた下垂体部膿瘍から脳室穿破に伸展した一例

高橋義秋, 山下徹, 佐々木諒, 田所功, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

臨床神経学 57 ( 10 ) 651 - 651 2017.10

Behavioral and affective features of amyotrophic lateral sclerosis patients Reviewed

Yasuyuki Ohta, Kota Sato, Mami Takemoto, Yoshiaki Takahashi, Ryuta Morihara, Yumiko Nakano, Keiichiro Tsunoda, Emi Nomura, Nozomi Hishikawa, Toni Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 381 119 - 125 2017.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Evaluating the cognitive and behavioral features in amyotrophic lateral sclerosis (ALS) patients is important for therapy and care. Fifty-seven ALS, 5 ALS with the behavioral variant of frontotemporal dementia (FTD) (ALS-FTD), 12 FTD patients, and 35 control subjects were evaluated by 10 different tests for cognitive and behavioral (mini-mental state examination (MMSE), Hasegawa dementia rating scale - revised (HDS-R), frontal assessment battery (FAB), Montreal cognitive assessment (MoCA), ALS-frontotemporal dementia-Questionnaire (ALS-FTD-Q), and anosognosia scale), affective (depression, apathy, and behavioral and psychological symptoms of dementia (BPSD)), and activities of daily living (ADL) assessments. The motor functions of ALS patients were evaluated by ALS functional rating scale - revised (ALSFRS-R) and modified Norris scale.ALS-FTD-Q scores showed intermediate behavioral disturbances of ALS patients between ALS-FTD and FTD patients and control subjects, but FAB, MoCA, and anosognosia scales did not. Both FAB and MoCA scores were significantly correlated with MMSE and HDS-R in ALS patients, but ALS-FTD-Q was not. ALS-FTD-Q score was significantly correlated with ALSFRS-R, apathy, BPSD, and ADL scores in ALS patients.Thus, in ALS patients, both FAB and MoCA tests were useful to assess frontal cognitive impairments, while ALS-FTD-Q was useful to detect mild behavioral and affective disturbances.

DOI： 10.1016/j.jns.2017.08.024

新しいSCA/ALS crossroad mutation AsidanのDWEP現象

太田康之, 山下徹, 佐藤恒太, 幡中典子, 角田慶一郎, 武本麻美, 菱川望, 阿部康二

日本難病医療ネットワーク学会機関誌 5 ( 1 ) 59 - 59 2017.9

Non-ketotic hyperosmolar coma after percutaneous endoscopic gastrostomy in an advanced stage of progressive supranuclear palsy

Koh Tadokoro, Kota Sato, Ryuta Morihara, Jingwei Shang, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Nozomi Hishikawa, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 5 ) 162 - 164 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Patients with progressive supranuclear palsy often suffer from dysphagia, and percutaneous endoscopic gastrostomy is a treatment option for the advanced stage of this disease. The present percutaneous endoscopic gastrostomy patient had slightly impaired glucose tolerance, but the condition became considerably worse with normal nutrients due to limited activity and an infection after percutaneous endoscopic gastrostomy, resulting in a non-ketotic hyperosmolar coma. After receiving supplementary fluid, intravenous insulin, antibiotics and endotracheal intubation, the patient recovered from the non-ketotic hyperosmolar coma state. Percutaneous endoscopic gastrostomy placement at an advanced stage of a neurodegenerative disorder, such as progressive supranuclear palsy, should have a careful follow-up, especially when glucose tolerance worsens.

DOI： 10.1111/ncn3.12139

Occult chronic progressive cervical and thoracic myelopathy without evident magnetic resonance imaging lesion

Emi Nomura, Toru Yamashita, Yoshiaki Takahashi, Keiichiro Tsunoda, Jingwei Shang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Hiroki Ueno, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 5 ) 155 - 158 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Progressive myelopathy is caused by infectious, inflammatory, autoimmune, paraneoplastic, demyelinating, vascular, hereditary, degenerative, metabolic and toxic properties. Here, we report a case of a 53-year-old woman who showed a progressive cervical and thoracic myelopathy with muscle weakness in all limbs, and hypoesthesia in all limbs and trunk below the Th8 level without any evident magnetic resonance imaging lesions. She displayed rheumatoid factor, anti-double stranded DNA antibody and hepatitis B surface antigen, as well as an elevated cerebrospinal fluid protein level. The paraneoplastic antibodies that we examined were negative. Our treatments (plasma exchange, steroid pulse therapy and immunoglobulin therapy) were slightly effective, but the symptoms did not improve completely. The present case suggests that the presence of a cervical and thoracic lesion without evident magnetic resonance imaging abnormalities required a careful follow up to discover occult lesions.

DOI： 10.1111/ncn3.12136

Case of myasthenia gravis and Lambert-Eaton myasthenic syndrome overlap syndrome accompanied by autoimmune encephalitis and cerebellar ataxia with multiple neuronal antibodies

Yumiko Nakano, Emi Nomura, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 5 ) 152 - 154 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

A 72-year-old woman developed a subacute series of encephalitis, cerebellar ataxia, and combined symptoms of both myasthenia gravis and Lambert-Eaton myasthenic syndrome. Seven different neuronal antibodies were detected for Hu, glutamic acid decarboxylase, acetylcholine receptor, P/Q-type voltage-gated calcium-channels, Zic4, Titin and SOX1 in her serum with intrathecal synthesis of glutamic acid decarboxylase antibodies. Although she showed classical manifestations with onconeural antibodies, she was diagnosed with not paraneoplastic but autoimmune neurological syndrome because of no underlying tumor and good response to immunotherapies. The present case is very unique and rare for complex neurological disorders including myasthenia gravis and Lambert-Eaton myasthenic syndrome overlap syndrome with multiple neuronal antibodies.

DOI： 10.1111/ncn3.12134

Dissociated recovery between dementia and parkinsonism by transvenous embolization of recurrent dural arteriovenous fistula

Yumiko Nakano, Emi Nomura, Masafumi Hiramatsu, Mami Takemoto, Kota Sato, Nozomi Hishikawa, Toru Yamashita, Yasuyuki Ohta, Kenji Sugiu, Isao Date, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 5 ) 159 - 161 2017.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Dementia and parkinsonism are rarely observed in dural arteriovenous fistula. Here, we report a case of a 63-year-old man with recurrent dural arteriovenous fistula, who developed progressive dementia and parkinsonism as a result of a dural arteriovenous fistula at the torcular herophili. A sinus thrombosis induced the abnormal cortical venous reflux from the isolated straight sinus, resulting in the deep venous congestion of the thalamus and basal ganglia, which led to dementia and parkinsonism. However, the third endovascular embolization ameliorated memory disturbance and apathy with a slight improvement of parkinsonism. Although recoveries from dural arteriovenous fistula-associated neurological deficits are variable depending on the severity, duration and, furthermore, selective vulnerability of the responsible ischemic lesions, early treatment should be essential for better recovery.

DOI： 10.1111/ncn3.12138

認知症の早期診断に有用な新しい簡易BPSDスコア(阿部式BPSDスコア=ABS)

阿部康二, 菱川望, 森原隆太, 中野由美子, 佐藤恒太, 武本麻美, 商敬偉, 山下徹

日本早期認知症学会誌 10 ( 3 ) 61 - 61 2017.8

Neuroprotective Effects of a Novel Antioxidant Mixture Twendee X in Mouse Stroke Model Reviewed

Momoko Kusaki, Yasuyuki Ohta, Haruhiko Inufusa, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Xia Liu, Jingwei Shang, Feng Tian, Yusuke Fukui, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 ( 6 ) 1191 - 1196 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Background: Oxidative stress and inflammation are important aggravating factors in acute ischemic stroke. Methods: In the present study, the neuroprotective effects of a novel antioxidant mixture Twendee X containing multiple antioxidative ingredients, such as coenzyme Q10, ascorbic acid, and cystine, were evaluated. After the pretreatment of a vehicle or Twendee X (20 mg/kg/d) for 14 days, mice were subjected to transient middle cerebral artery occlusion for 60 minutes and further treated with vehicle or Twendee X for 1 or 5 days. Results: Twendee X administration reduced the infarct size, and reduced oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine,4-hydroxy-2-nonenal, and N-epsilon-(carboxymethyl) lysine (one of advanced glycation end products), as well as inflammatory markers such as ionized calcium binding adapter molecule-1, tumor necrosis factor-alpha, and monocyte chemotactic protein-1. Conclusions: In the present study, the neuroprotective effects of Twendee X were shown on transient middle cerebral artery occlusion mice via antioxidative and anti-inflammatory pathways, providing a potential of Twendee X as one preventive and therapeutic treatment. (C) 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jstrokecerebrovasdis.2017.01.003

Different Characteristics of Anterior and Posterior Branch Atheromatous Diseases with or without Early Neurologic Deterioration Reviewed

Yoshiaki Takahashi, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Yasuhiro Manabe, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 26 ( 6 ) 1314 - 1320 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: Among several types of ischemic stroke (IS), branch atheromatous disease (BAD) is known to be the leading cause of disability. Methods: A total of 1919 patients with acute IS were retrospectively analyzed, and BAD patients were classified into anterior or posterior BAD, depending on the responsible vascular territories. These patients were further subcategorized with or without early neurologic deterioration (END or no-END). Results: Of all IS patients, 14.3% had BAD, and 202 patients (73.7%) were further classified as anterior BAD and 72 patients (26.3%) as posterior BAD. The prevalence of diabetes mellitus and END was significantly higher in posterior than in anterior BAD (44.4% vs 26.4%, P <.01; 18.1% vs 5.4%, P <.01, respectively). Posterior BAD showed a higher proportion of female patients and an older age (69.2% vs 39.0%, P <.05; 79.1 +/- 7.7 vs 70.5 +/- 10.7, P <.01, respectively) in END than in no-END. The modified Rankin Scale was worse in posterior BAD at 90 days (2.5 +/- 1.6, P <.01) than in anterior BAD (1.6 +/- 1.4). Conclusions: Our present study shows that posterior BAD is a worse clinical outcome than anterior BAD, with more vascular risk factors. Older female patients with posterior BAD showed a higher risk of END, leading to a worse clinical outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2017.02.001

Factors related to continuous and discontinuous attendance at memory clinics Reviewed

N. Hishikawa *,Y. Fukui ,Y. Nakano ,R. Morihara ,M. Takemoto *,K. Sato *,T. Yamashita *,Y. Ohta *,K. Abe *

European Journal of Neurology 24 ( 5 ) 673 - 679 2017.5

Familial amyotrophic lateral sclerosis of the G37V-superoxide dismutase 1 mutation with a slow disease progression

Koh Tadokoro, Yasuyuki Ohta, Yoshiaki Takahashi, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Koji Abe

NEUROLOGY AND CLINICAL NEUROSCIENCE 5 ( 3 ) 96 - 98 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

The majority of amyotrophic lateral sclerosis patients have the sporadic form, but 5-10% of those have familial amyotrophic lateral sclerosis. A total of 15-20% of familial amyotrophic lateral sclerosis patients have genetic mutations in the superoxide dismutase 1 gene. In 2012, Kobayashi et al. reported the first case of a familial amyotrophic lateral sclerosis patient carrying a G37V superoxide dismutase 1 mutation, who showed rapid progression and died within 1.2 years of onset from respiratory failure. In contrast, here we report the second case of familial amyotrophic lateral sclerosis carrying the G37V superoxide dismutase 1 mutation, showing a very slow progression, and his father and aunt also had longer disease durations from 4 to 6 years. Further clinical and biological studies will clarify the detailed pathological role of the G37V superoxide dismutase 1 mutation for amyotrophic lateral sclerosis.

DOI： 10.1111/ncn3.12123

Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype Reviewed

Toru Yamashita, Jun Mitsui, Nobuyuki Shimozawa, Shigeo Takashima, Hiroshi Umemura, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Takashi Matsukawa, Hiroyuki Ishiura, Jun Yoshimura, Koichiro Doi, Shinichi Morishita, Shoji Tsuji, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 375 424 - 429 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Peroxisome biogenesis factor 10 (PEX10) is involved in the import of peroxisomal matrix proteins, and the mutation of this gene causes 3 subtypes of peroxisome biogenesis disorders, namely Zellweger syndrome (severe), neonatal adrenoleukodystrophy (moderate) and an ataxic form (mild). Here, we report 3 siblings of the ataxic form with cerebellar ataxia, mild mental retardation, and 3 additional characteristic features: mydriasis, hyperreflexia and involuntary head movement. All 3 siblings are compound heterozygous for a previously reported mutation, c.2T>C (p.M1T), and a novel mutation, c920G>A, causing a missense change (p.C307Y) located in the RING finger domain of PEX10. The present cases suggest that these PEX10 mutations involve not only cerebellar but also more multiple nervous systems including pupillary autonomic, pyramidal and extrapyramidal systems. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2017.02.058

Potential multisystem degeneration in Asidan patients Reviewed

Yasuyuki Ohta, Toru Yamashita, Nozomi Hishikawa, Kota Sato, Kosuke Matsuzono, Keiichiro Tsunoda, Noriko Hatanaka, Mami Takemoto, Toshihiko Takemi, Kazuhiro Takamatsu, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 373 216 - 222 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objective: To evaluate a potential multisystem involvement of neurodegeneration in Asidan, in addition to cerebellar ataxia and signs of motor neuron disease.Methods: We compared the new Asidan patients and those identified in previous studies with Parkinson's disease (PD, n = 21), and progressive supranuclear palsy (PSP, n = 13) patients using I-123-2 beta-Carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (I-123-FP-CIT) dopamine transporter single photon emission computed tomography (DAT-SPECT) and I-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy (Asidan, DAT: n = 10; MIBG: n = 15).Results: Both the PD and PSP groups served as positive controls for DAT decline. The PD and PSP groups served as a positive and negative control, respectively, of MIBG decline in the early phase H/M ratio. Of the Asidan patients, 60.0% showed DAT decline without evident parkinsonian features and 6.7% showed impaired MIBG in only the delayed phase H/M ratio. Combined with a normal range of the early phase H/M ratio, this phenotype was newly named Declined DAT Without Evident Parkinsonism (DWEP).Interpretation: The results of present study including DWEP suggest a wider spectrum of neurodegeneration for extrapyramidal and autonomic systems in Asidan patients than expected, involving cerebellar, motor system and cognitive functioning. (C) 2017 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2017.01.003

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) with Limbic Encephalitis Reviewed

Yasuyuki Ohta, Emi Nomura, Keiichiro Tsunoda, Toru Yamashita, Yoshiaki Takahashi, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Koji Abe

INTERNAL MEDICINE 56 ( 18 ) 2513 - 2518 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids ( CLIPPERS) is an inflammatory central nervous system disorder that mainly involves in the brainstem, basal ganglia and cerebellum. We herein report the case of a patient with CLIPPERS, which was diagnosed based on the clinical and radiological features. After initially responded to steroid treatment, the patient developed limbic encephalitis. The patient presented with memory disturbance, a delirious state and emotional incontinence. A cerebrospinal fluid study revealed interleukin-6 elevation and enhanced bilateral hippocampal lesions were observed on MRI. The patient was successfully treated with methylprednisolone pulse therapy. This is the first case of CLIPPERS with limbic encephalitis involving the bilateral hippocampus.

DOI： 10.2169/internalmedicine.8533-16

Emergency caesarean section saved both an anti-musk antibody-positive myasthenia gravis mother with pregnancy-induced hypertension and her premature baby

Yoshiaki Takahashi, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Kei Hayata, Hisashi Masuyama, Tomoka Okamura, Yosuke Washio, Koji Abe

Internal Medicine 56 ( 24 ) 3361 - 3364 2017

Publishing type：Research paper (scientific journal)

© 2017 The Japanese Society of Internal Medicine. We herein report the case of a 46-year-old pregnant woman with anti-muscle specific kinase (MuSK) antibody-positive myasthenia gravis (MG) who showed pregnancy-induced hypertension and developed respiratory failure at 30 weeks and 5 days of pregnancy, and who underwent an emergency caesarean section (CS). Her MG symptoms gradually improved in the subsequent weeks. The premature baby with positive MuSK antibodies was successfully delivered, but the male baby required temporary artificial ventilation. However, his condition also gradually improved over time. The present case suggests that an emergency CS could rescue both the mother, who was in critical condition, and the prematurely born baby, even when suffering from acute respiratory insufficiency.

DOI： 10.2169/internalmedicine.8636-16

アルツハイマー病患者におけるガランタミンの長期的効果について

中野由美子, 山下徹, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 阿部康二

Anti-aging Science 8 ( 1 ) 69 - 69 2016.12

脳血管性認知症モデルラットにおけるテルミサルタンの治療効果

山下徹, 菱川望, 佐藤恒太, 武本麻美, 太田康之, 阿部康二

Anti-aging Science 8 ( 1 ) 72 - 72 2016.12

難病患者就労に対する山陽神経難病ネットワークの役割

太田康之, 山下徹, 菱川望, 佐藤恒太, 武本麻美, 阿部康二, 三宅進, 重實比呂子, 三村あゆみ, 三垣亮輔, 竹内秀将, 岩藤弘子, 薮田智子, 斎藤文恵, 鈴木美穂, 竹内ひかり

日本難病医療ネットワーク学会機関誌 4 ( 1 ) 61 - 61 2016.11

ラット一過性脳虚血モデルにおけるTDP43とFUS/TLSの発現亢進による神経細胞保護効果について

中野由美子, Sun Miao, 山下徹, 森原隆太, 武本麻美, 佐藤恒太, 菱川望, 太田康之, 阿部康二

脳循環代謝 28 ( 1 ) 232 - 232 2016.11

多発脳神経麻痺が急速に進行した腎癌の頭蓋底転移の1剖検例

武本麻美, 河原由子, 佐藤恒太, 佐藤康晴, 太田康之, 菱川望, 山下徹, 阿部康二

日本老年医学会雑誌 53 ( 4 ) 461 - 461 2016.10

Asidan(ALS/SCA crossroad mutation)はSWEDDsと正反対所見DWEPを呈する

阿部康二, 太田康之, 山下徹, 菱川望, 佐藤恒太, 武本麻美

パーキンソン病・運動障害疾患コングレスプログラム・抄録集 10回 84 - 84 2016.10

PDDとDLB患者の認知機能・情動機能・日常生活活動強度の比較

武本麻美, 菱川望, 太田康之, 山下徹, 佐藤恒太, 幡中典子

パーキンソン病・運動障害疾患コングレスプログラム・抄録集 10回 88 - 88 2016.10

Temporal Profiles of Stress Protein Inductions after Focal Transient Ischemia in Mice Brain Reviewed

Qian Li, Yumiko Nakano, Jingwei Shang, Yasuyuki Ohta, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Koji Abe

JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 25 ( 10 ) 2344 - 2351 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Background: Stress proteins have been found to play important protective roles against ischemic brain injury under hypoxic, oxidative, heat shock, and proteasome stresses. Methods: In the present study, we investigated the temporal profiles of the major stress proteins including hypoxia-inducible factor-1 alpha (HIF-1 alpha), glutathione (GSH), heat shock protein 72 (HSP72), constitutive heat shock cognate protein 73 (HSC73), and ubiquitin after 45 minutes of transient middle cerebral artery occlusion (tMCAO) in the mice brain up to 7 days after reperfusion. Results: Immunohistochemical analyses of HIF-1 alpha, GSH, HSP72, and ubiquitin showed little immunoreactivity of neural cells in sham control brain, whereas HSC73 showed a constitutive immunoreactivity. After tMCAO, HSC73 showed the fastest increase at 12 hours in the peri-ischemic area, followed by HIF-1 alpha with a peak at 24 hours, GSH, HSP72, and ubiquitin with a peak at 72 hours. All these stress proteins returned toward the baseline levels until 7 days. In the ischemic core, these stress proteins showed a similar change with less reaction compared to the peri-ischemic area. Conclusions: These data showed temporal expressions of HIF-1 alpha, GSH, HSP72, HSC73, and ubiquitin in the mice brain after tMCAO, which might provide a better understanding of neuroprotective mechanisms and novel targets for therapeutic intervention of brain ischemic disease. (C) 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.jstrokecerebrovasdis.2016.05.031

Differences between the behavioral and psychological symptoms of Alzheimer's disease and Parkinson's disease Reviewed

Ryo Tokuchi, Nozomi Hishikawa, Kota Sato, Noriko Hatanaka, Yusuke Fukui, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 369 278 - 282 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Aim: We compared the behavioral and psychological symptoms of Alzheimer's disease (AD) and Parkinson's disease (PD) in order to determine the characteristic features of each disorder.Methods: For this retrospective cohort study, we compared the behavioral and psychological symptoms of 288 AD patients and 189 PD patients (mean age, 74.6 +/- 5.9 and 73.0 +/- 8.7 years respectively). Symptoms were evaluated using the geriatric depression scale (GDS), apathy scale (AS), and Abe's behavioral and psychological symptoms of dementia score (ABS).Results: AD patients had higher AS and ABS scores than PD patients. A gender-dependent comparison showed that ABS scores were worse in female AD patients than in female PD patients (p=0.001). A subscale analysis of ABS scores revealed that male AD patients were only significantly different from male PD patients in I item, whereas female AD patients were significantly different from female PD patients in 4 items. Among patients with mild cognitive decline, no differences in affective scores were observed. Alternatively, among patients with moderate cognitive decline, affective scores on all 3 scales were worse in PD patients than in AD patients.Conclusions: The present age-and gender-matched retrospective analysis identified greater behavioral and psychological disease severity in female AD patients relative to female PD patients, and greater affective severity in PD patients versus AD patients with a similar degree of cognitive decline. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.08.053

Comparative Gait Analysis in Progressive Supranuclear Palsy and Parkinson's Disease Reviewed

Noriko Hatanaka, Kota Sato, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

European Neurology 75 ( 5-6 ) 282 - 289 2016.7

Language：English Publishing type：Research paper (scientific journal)

© 2016 S. Karger AG, Basel. Background: Although changes to gait are an important clinical feature of progressive supranuclear palsy (PSP), systematic analyses have not been well examined, especially in comparison to Parkinson's disease (PD). Methods: The characteristics of gait in 20 PSP patients (14 males and 6 females) were evaluated in comparison to 124 PD patients (64 males and 60 females) and 24 controls, that is, healthy age-matched adults (5 males and 19 females). Gait in patients was recorded in a 10-m walking test at a self-selected speed. During this time, patients felt most comfortable while wearing a new portable triaxial accelerometer rhythmogram device. Gait variables among the 3 groups were compared. Results: Both PSP and PD patients shared the following similar hypokinetic gait characteristics: decreased velocity, step length, cadence and mean acceleration. Step time and variability in step time were mutually related. However, among the 3 groups, PSP patients showed characteristically low vertical displacement and a higher acceleration than PD patients at the same cadence. Conclusion: Although PSP and PD patients showed similar hypokinetic gait, a reduced vertical displacement characterized walking in PSP patients, differing substantially from the characteristics of walking displayed by PD patients.

DOI： 10.1159/000445111

脳血管性認知症モデルラットにおけるテルミサルタンの治療効果

山下徹, 菱川望, 佐藤恒太, 武本麻美, 太田康之, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 16回 191 - 191 2016.6

Age-dependent cognitive and affective differences in Alzheimer's and Parkinson's diseases in relation to MRI findings Reviewed

Ryo Tokuchi, Nozomi Hishikawa, Kota Sato, Noriko Hatanaka, Yusuke Fukui, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

JOURNAL OF THE NEUROLOGICAL SCIENCES 365 3 - 8 2016.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objective: To compare age-dependent changes in cognitive and affective functions related to white matter changes between patients with Alzheimer's disease (AD) and Parkinson's disease (PD).Methods: We retrospectively compared age-dependent cognitive and affective functions in 216 AD patients, 153 PD patients, and 103 healthy controls with cerebral white matter lesions (WMLs), periventricular hyperintensity (PVH), deep white matter hyperintensity (DWMH), micro-bleeds (MBs), and lacunar infarcts (LIs).Results: The average mini-mental state examination (MMSE) scores were 19.6 +/- 6.1 and 26.8 +/- 3.6 in AD and PD patients, respectively. Significant decreases were found in the MMSE score, Hasegawa's dementia scale-revised (HDS-R) score, frontal assessment battery score, and Abe's BPSD score (ABS) among the age-dependent AD subgroups and in the MMSE, HDS-R, Montreal cognitive assessment, geriatric depression scale, and ABS scores among the age-dependent PD subgroups; they were worse in AD patients. White matter changes were observed in > 88% and > 72% of patients with AD and PD, respectively. An age-dependent direct comparison of AD and PD showed significant differences in the PVH and DWMH grades, and numbers of MBs and LIs.Conclusion: WML-related cognitive and affective functions worsen with age in AD and PD patients; however, the abnormalities were more frequent and stronger in AD patients. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.03.031

New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy

Zhuoran Sun, Yasuyuki Ohta, Toru Yamashita, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Koji Abe

Neurology: Genetics 2 ( 2 ) 2016.4

Publishing type：Research paper (scientific journal)

© 2016 American Academy of Neurology. Objective: The aim of this study was to analyze the association between the variations of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene (COQ2) and Japanese patients with multiple system atrophy (MSA). Methods: We investigated the genetic variations in exons 1, 2, 6, and 7 of the COQ2 gene in 133 Japanese patients with MSA and 200 controls and analyzed the association between the variations and MSA. Results: Six DNA variations (G21S, L25V, V66L, P157S, V393A, and X422K) were found in the 133 patients with MSA, and G21S and X422K were new variations that had never been reported. V66L was a common variation that was found in all 133 patients with MSA. G21S, P157S, V393A, and X422K did not show gene frequency differences between patients with MSA and controls. On the other hand, L25V was newly proven to be the only risk factor of sporadic MSA with predominant olivopontocerebellar ataxia. Conclusions: The present study suggests L25V variant of COQ2 gene as a genetic risk factor in Japanese patients with MSA with cerebellar ataxia.

DOI： 10.1212/NXG.0000000000000054

Comparative Gait Analysis in Progressive Supranuclear Palsy and Parkinson's Disease

Noriko Hatanaka, Kota Sato, Nozomi Hishikawa, Mami Takemoto, Yasuyuki Ohta, Toru Yamashita, Koji Abe

EUROPEAN NEUROLOGY 75 ( 5-6 ) 282 - 289 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：KARGER

Background: Although changes to gait are an important clinical feature of progressive supranuclear palsy (PSP), systematic analyses have not been well examined, especially in comparison to Parkinson's disease (PD). Methods: The characteristics of gait in 20 PSP patients (14 males and 6 females) were evaluated in comparison to 124 PD patients (64 males and 60 females) and 24 controls, that is, healthy age-matched adults (5 males and 19 females). Gait in patients was recorded in a 10-m walking test at a self-selected speed. During this time, patients felt most comfortable while wearing a new portable triaxial accelerometer rhythmogram device. Gait variables among the 3 groups were compared. Results: Both PSP and PD patients shared the following similar hypokinetic gait characteristics: decreased velocity, step length, cadence and mean acceleration. Step time and variability in step time were mutually related. However, among the 3 groups, PSP patients showed characteristically low vertical displacement and a higher acceleration than PD patients at the same cadence. Conclusion: Although PSP and PD patients showed similar hypokinetic gait, a reduced vertical displacement characterized walking in PSP patients, differing substantially from the characteristics of walking displayed by PD patients. (C) 2016 S. Karger AG, Basel

DOI： 10.1159/000445111

Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson's Disease with Dementia and Dementia with Lewy Bodies Reviewed

Mami Takemoto, Kota Sato, Noriko Hatanaka, Toru Yamashita, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe

JOURNAL OF ALZHEIMERS DISEASE 52 ( 1 ) 205 - 211 2016

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：IOS PRESS

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2 +/- 4.8) and better frontal assessment battery (FAB) scores (11.3 +/- 4.1) compared with DLB (17.0 +/- 6.4, p = 0.013 and 8.6 +/- 4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in "orientation to place" tasks. In affective functions, DLB patients had worse GDS (7.6 +/- 3.4) and ABS (9.9 +/- 5.3) scores than PDD patients (5.1 +/- 4.1 and 4.8 +/- 3.0, respectively). Tc-99m-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients' lower average scores for "repetition" (MMSE), "recent memory" (HDS-R), and "lexical fluency" (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients' poorer average subscale scores of " orientation to place" (MMSE) and "similarities", "conflicting instructions", and "go-no go" (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD.

DOI： 10.3233/JAD-150952

多発性硬化症および視神経脊髄炎におけるタッチパネル式認知機能検査の有用性

太田康之, 河原由子, 薮田智子, 竹内ひかり, 佐藤恒太, 武本麻美, 菱川望, 山下徹, 阿部康二

日本難病医療ネットワーク学会機関誌 3 ( 1 ) 55 - 55 2015.11

脳卒中慢性期患者では再発よりも認知症移行(direct conversion)が高い

中野由美子, 出口健太郎, 山下徹, 武本麻美, 佐藤恒太, 菱川望, 太田康之, 高尾芳樹, 東靖人, 阿部康二

脳循環代謝 27 ( 1 ) 149 - 149 2015.10

進行性核上性麻痺・パーキンソン病患者における歩行の比較

幡中典子, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 山下徹, 阿部康二

パーキンソン病・運動障害疾患コングレスプログラム・抄録集 9回 81 - 81 2015.10

テルミサルタン長期投与がラット梗塞後脳に及ぼすメタボリックシンドローム関連因子発現の検討

出口健太郎, ざい蘊, 佐藤恒太, 武本麻美, 菱川望, 太田康之, 山下徹, 阿部康二

脳循環代謝 27 ( 1 ) 195 - 195 2015.10

多発性硬化症および視神経脊髄炎におけるタッチパネル式認知機能検査の検討

太田康之, 河原由子, 佐藤恒太, 武本麻美, 菱川望, 山下徹, 阿部康二

Dementia Japan 29 ( 3 ) 404 - 404 2015.9

PDDとDLBの認知機能、情動機能の比較検討

武本麻美, 菱川望, 太田康之, 山下徹, 佐藤恒太, 幡中典子, 阿部康二

日本神経心理学会総会プログラム・予稿集 39回 204 - 204 2015.8

MCIの予後と関連因子の検討

徳地亮, 菱川望, 佐藤恒太, 幡中典子, 武本麻美, 福井裕介, 太田康之, 山下徹, 阿部康二

日本抗加齢医学会総会プログラム・抄録集 15回 190 - 190 2015.5

タッチパネル式コンピュータを活用した脳梗塞既往患者の認知機能と画像所見の関連の検討

出口健太郎, 河野祥一郎, 柚木太淳, 松薗構佑, 中野由美子, 角田慶一郎, 河原由子, 幡中典子, 武本麻美, 太田康之, 菱川望, 山下徹, 阿部康二

脳循環代謝 26 ( 1 ) 168 - 168 2014.11

側頭葉内側萎縮と大脳白質病変の併存がアルツハイマー病患者の認知機能と情動機能に及ぼす影響

徳地亮, 菱川望, 佐藤恒太, 幡中典子, 武本麻美, 福井裕介, 太田康之, 出口健太郎, 山下徹, 阿部康二

脳循環代謝 26 ( 1 ) 214 - 214 2014.11

Myocardial microvascular perfusion after transfusion of liposome-encapsulated hemoglobin evaluated in cross-circulated rat hearts using tracer digital radiography

Takahisa Asano, Takeshi Matsumoto, Hiroyuki Tachibana, Mami Takemoto, Fumihiko Kajiya

Journal of Artificial Organs 7 ( 3 ) 145 - 148 2004.9

Language：English Publishing type：Research paper (scientific journal)

The effect of hemodilution with Neo Red Cell (NRC, liposome-encapsulated hemoglobin) on myocardial perfusion was evaluated in cross-circulated rat hearts under 300-bpm pacing and 100-mmHg perfusion pressure. In NRC-transfused hearts (n = 5), NRC volume fraction and hematocrit were 9% ± 3% and 22% ± 4%, respectively
the latter decreased from 43% ± 3% before NRC transfusion. Coronary perfusion rate and left ventricular isovolemic developed pressure increased after NRC transfusion to 4.6 ± 1.0 ml/min/g and 127 ± 32 mmHg from basal values of 2.5 ± 0.3 ml/min/g and 115 ± 28 mmHg, respectively. In contrast, the flow increase during reperfusion following 30-s flow cessation decreased from 74% ± 24% to 64% ± 24%. The arteriovenous difference in O2 saturation was slightly higher after NRC transfusion. Within-layer regional flow distributions from subepicardium to subendocardium assessed by tracer digital radiography (100-μm resolution) showed that coefficients of variation of flows in 400 X 400-μm regions were 0.41 ± 0.10 in NRC-transfused hearts and 0.54 ± 0.11 in nontransfused hearts (n = 5)
i.e., the myocardial flow distribution was more uniform in NRC-transfused hearts. These results suggest that NRC is superior to erythrocytes in terms of the homogenization of O 2 delivery, indicating its potential therapeutic value in myocardial microcirculatory failure.

DOI： 10.1007/s10047-004-0260-1

Pattern differences between distributions of microregional myocardial flows in crystalloid- and blood-perfused rat hearts

Takeshi Matsumoto, Hiroyuki Tachibana, Takahisa Asano, Mami Takemoto, Yasuo Ogasawara, Keiji Umetani, Fumihiko Kajiya

American Journal of Physiology - Heart and Circulatory Physiology 286 ( 4 ) H1331 - H1338 2004

Language：English Publishing type：Research paper (scientific journal)

Regional myocardial flow distributions in Langendorff rat hearts under Tyrode and blood perfusion were assessed by tracer digital radiography (100-μm resolution). Flow distributions during baseline and maximal hyperemia following a 60-s flow cessation were evaluated by the coefficient of variation of regional flows (CV
related to global flow heterogeneity) and the correlation between adjacent regional flows (CA
inversely related to local flow randomness). These values were obtained for the original images (64 2 pixels) and for coarse-grained images (322, 16 2, and 82 blocks of nearby pixels). At a given point in time during baseline, both CV and CA were higher in blood (n = 7) than in Tyrode perfusion (n = 7) over all pixel aggregates (P &lt
0.05, two-way ANOVA). During the maximal hyperemia, CV and CA were still significantly higher in blood (n = 7) than in Tyrode perfusion (n = 7)
however, these values decreased substantially in blood perfusion and the CV and CA differences became smaller than those at baseline accordingly. During basal blood perfusion, the 60-s average flow distribution (n = 7) showed a smaller CV and CA than those at a given point in time (P &lt
0.05, two-way ANOVA). Coronary flow reserve was significantly higher in blood than in Tyrode perfusion. In conclusion, the flow heterogeneity and the local flow similarity are both higher in blood than in Tyrode perfusion, probably due to the different degree of coronary tone preservation and the presence or absence of blood corpuscles. Under blood perfusion, temporal flow fluctuations over 60-s order are largely involved in shaping microregional flow distributions.

DOI： 10.1152/ajpheart.00120.2003

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