2021/12/04 更新

写真a

ウエムラ マサヒロ
上村 昌寛
UEMURA Masahiro
所属
医歯学総合病院 脳神経内科 助教
職名
助教
連絡先
メールアドレス
外部リンク

学位

  • 医学 ( 2018年3月   新潟大学 )

  • 医学 ( 2006年3月   弘前大学 )

経歴

  • 新潟大学   医歯学総合病院 脳神経内科   助教

    2020年2月 - 現在

  • 新潟大学   医歯学総合病院 脳神経内科   特任助教

    2019年4月 - 2020年1月

  • 新潟大学   医歯学総合病院 神経内科   特任助教

    2018年4月 - 2019年3月

  • 新潟大学   医歯学総合病院 高次救命災害治療センター   特任助教

    2013年4月 - 2015年3月

 

論文

  • [Rethinking Lacunar Stroke: Beyond Fisher's Curse].

    Osamu Onodera, Masahiro Uemura, Shoichiro Ando, Hideki Hayashi, Masato Kanazawa

    Brain and nerve = Shinkei kenkyu no shinpo   73 ( 9 )   991 - 998   2021年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Lipohyalinosis is an important concept in the independence of lacunar stroke; however, its role has been overemphasized and has led to much confusion in the understanding of lacunar stroke. Classical lipohyalinosis has declined following the widespread availability of antihypertensive therapy, and lacunar stroke secondary to age-related hyaline atherosclerosis is more commonly observed in clinical practice. Clinically diagnosed lacunar stroke is associated with several etiopathogenetic contributors. Excluding cardiogenic embolism, lacunar stroke can be categorized based on the detection of an atheroma. Atheroma imaging is possible in recent years, and strokes that are not associated with an atheroma are shown to present with deep white matter hyperintensity on MRI. Additionally, risk gene analysis has confirmed a group of risk genes associated with the extracellular matrix in lacunar stroke with white matter hyperintensity on MRI. These findings suggest the role of a variety of etiopathogenetic mechanisms underlying lacunar stroke and that lacunar stroke with deep white matter hyperintensity on MRI may be attributable to unique pathogenetic contributors. This group is known to be strongly associated with genetic contributors. Hopefully, lacunar stroke will be diagnosed from this perspective with the development of interventional strategies tailored to the pathogenesis of this condition.

    DOI: 10.11477/mf.1416201876

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  • Corrigendum: HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade. 国際誌

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in neurology   12   756038 - 756038   2021年

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    記述言語:英語  

    [This corrects the article DOI: 10.3389/fneur.2019.00693.].

    DOI: 10.3389/fneur.2021.756038

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  • Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review 国際誌

    Yutaka Otsu, Masaki Namekawa, Masafumi Toriyabe, Itaru Ninomiya, Masahiro Hatakeyama, Masahiro Uemura, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

    Journal of the Neurological Sciences   419   117217 - 117217   2020年12月

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    記述言語:英語  

    Background: Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma. Aim: To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS. Methods: A literature review was performed using PubMed and the ClinicalTrials.gov database. Results: Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected. Conclusion: To fully utilize the easily accessible drug—tPA—and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents.

    DOI: 10.1016/j.jns.2020.117217

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  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性の検討

    二宮 格, 金澤 雅人, 上村 昌寛, 小野寺 理

    脳循環代謝   32 ( 1 )   113 - 113   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本脳循環代謝学会  

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  • ラクナ梗塞とBranch atheromatous diseaseの鑑別における、入院時血清PTX3値の有用性

    金澤 雅人, 二宮 格, 上村 昌寛, 下畑 享良, 小野寺 理

    臨床神経学   60 ( Suppl. )   S360 - S360   2020年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature 国際誌

    Masahiro Uemura, Hiroaki Nozaki, Taisuke Kato, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Nozomi Hishikawa, Yoshinori Nishimoto, Kiran Polavarapu, Atchayaram Nalini, Akira Hanazono, Daisuke Kuzume, Akihiro Shindo, Mohammad El-Ghanem, Arata Abe, Aki Sato, Mari Yoshida, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    Frontiers in Neurology   11   545 - 545   2020年7月

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    記述言語:英語  

    Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is clinically characterized by early-onset dementia, stroke, spondylosis deformans, and alopecia. In CARASIL cases, brain magnetic resonance imaging reveals severe white matter hyperintensities (WMHs), lacunar infarctions, and microbleeds. CARASIL is caused by a homozygous mutation in high-temperature requirement A serine peptidase 1 (HTRA1). Recently, it was reported that several heterozygous mutations in HTRA1 also cause cerebral small vessel disease (CSVD). Although patients with heterozygous HTRA1-related CSVD (symptomatic carriers) are reported to have a milder form of CARASIL, little is known about the clinical and genetic differences between the two diseases. Given this gap in the literature, we collected clinical information on HTRA1-related CSVD from a review of the literature to help clarify the differences between symptomatic carriers and CARASIL and the features of both diseases. Forty-six symptomatic carriers and 28 patients with CARASIL were investigated. Twenty-eight mutations in symptomatic carriers and 22 mutations in CARASIL were identified. Missense mutations in symptomatic carriers are more frequently identified in the linker or loop 3 (L3)/loop D (LD) domains, which are critical sites in activating protease activity. The ages at onset of neurological symptoms/signs were significantly higher in symptomatic carriers than in CARASIL, and the frequency of characteristic extraneurological findings and confluent WMHs were significantly higher in CARASIL than in symptomatic carriers. As previously reported, heterozygous HTRA1-related CSVD has a milder clinical presentation of CARASIL. It seems that haploinsufficiency can cause CSVD among symptomatic carriers according to the several patients with heterozygous nonsense/frameshift mutations. However, the differing locations of mutations found in the two diseases indicate that distinct molecular mechanisms influence the development of CSVD in patients with HTRA1-related CSVD. These findings further support continued careful examination of the pathogenicity of mutations located outside the linker or LD/L3 domain in symptomatic carriers.

    DOI: 10.3389/fneur.2020.00545

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  • Elevated serum pentraxin 3 levels might predict the diagnosis of branch atheromatous disease at a very early stage

    I. Ninomiya, M. Kanazawa, M. Uemura, O. Onodera

    European Journal of Neurology   27 ( 7 )   1279 - 1284   2020年7月

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    掲載種別:研究論文(学術雑誌)  

    Background and purpose: Branch atheromatous disease (BAD) is one of the stroke subtypes caused by occlusion at the origin of a deep penetrating artery of the brain and is associated with a microatheroma or a junctional plaque. Patients with BAD often develop progressive worsening of neurologic deficits, although these patients often present minor stroke with clinical characteristics of lacunar syndrome at the onset. Pentraxin 3 (PTX3) is known to be a key molecule involved in the pathogenesis of atherosclerosis. Although a high level of serum PTX3 is observed in patients with acute coronary syndrome, there are no reports on PTX3 levels in patients with BAD. This study aimed to investigate whether serum PTX3 levels can distinguish BAD from other stroke subtypes. Methods: We investigated 93 patients with ischaemic stroke. Serum PTX3 levels on admission were measured using enzyme-linked immunosorbent assay in patients with BAD and those with other stroke subtypes (each n ≥ 20). Results: The median PTX3 levels in patients with BAD (4840 pg/mL) were higher than those with other subtypes of stroke (3397 pg/mL in lacunar stroke, 1298 pg/mL in large-artery atherosclerosis, 1470 pg/mL in cardioaortic embolism and 1006 pg/mL in control) (all P < 0.01). Conclusion: Our results suggest that elevated serum PTX3 levels might predict the diagnosis of BAD at a very early stage.

    DOI: 10.1111/ene.14249

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  • Excessive Production of Transforming Growth Factor β1 Causes Mural Cell Depletion From Cerebral Small Vessels 国際誌

    Taisuke Kato, Yumi Sekine, Hiroaki Nozaki, Masahiro Uemura, Shoichiro Ando, Sachiko Hirokawa, Osamu Onodera

    Frontiers in Aging Neuroscience   12   151 - 151   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    It is increasingly becoming apparent that cerebrovascular dysfunction contributes to the pathogenic processes involved in vascular dementia, Alzheimer’s disease, and other neurodegenerative disorders. Under these pathologic conditions, the degeneration of cerebral blood vessels is frequently accompanied by a loss of mural cells from the vascular walls. Vascular mural cells play pivotal roles in cerebrovascular functions, such as regulation of cerebral blood flow and maintenance of the blood-brain barrier (BBB). Therefore, cerebrovascular mural cell impairment is involved in the pathophysiology of vascular-related encephalopathies, and protecting these cells is essential for maintaining brain health. However, our understanding of the molecular mechanism underlying mural cell abnormalities is incomplete. Several reports have indicated that dysregulated transforming growth factor β (TGFβ) signaling is involved in the development of cerebral arteriopathies. These studies have specifically suggested the involvement of TGFβ overproduction. Although cerebrovascular toxicity via vascular fibrosis by extracellular matrix accumulation or amyloid deposition is known to occur with enhanced TGFβ production, whether increased TGFβ results in the degeneration of vascular mural cells in vivo remains unknown. Here, we demonstrated that chronic TGFβ1 overproduction causes a dropout of mural cells and reduces their coverage on cerebral vessels in both smooth muscle cells and pericytes. Mural cell degeneration was also accompanied by vascular luminal dilation. TGFβ1 overproduction in astrocytes significantly increased TGFβ1 content in the cerebrospinal fluid (CSF) and increased TGFβ signaling-regulated gene expression in both pial arteries and brain capillaries. These results indicate that TGFβ is an important effector that mediates mural cell abnormalities under pathological conditions related to cerebral arteriopathies.

    DOI: 10.3389/fnagi.2020.00151

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  • 一側視野に限局した複雑幻視を呈した硬膜動静脈瘻の1例

    小出 眞悟, 畠山 公大, 上村 昌寛, 菊池 文平, 長谷川 仁, 小野寺 理

    臨床神経学   60 ( 6 )   425 - 428   2020年6月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

    右側視野内に視野欠損を伴わない複雑幻視を呈した76歳の女性。脳波検査ではT5、P3を焦点とする鋭一過性波を認めた。頭部MRIでは左下部側頭葉を中心に左側頭後頭葉白質に信号変化を認めた。脳血管造影法で左後頭動脈から左横静脈洞に血流を認め、硬膜動静脈瘻(dural arteriovenous fistula;DAVF)と診断した。経動脈塞栓術後に複雑幻視は消失した。本症例の幻視はDAVFに伴うてんかん発作や皮質の血流変化による可能性を考えた。一般に複雑幻視は、てんかん性幻視は全視野にわたって出現し、一側性の場合は欠損視野内に出現する盲視野内幻視となる。本例は視野欠損を伴わずに一側性の複雑幻視が生じた点、DAVFが複雑幻視を呈した点で、貴重な症例と考えた。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01550&link_issn=&doc_id=20200615340005&doc_link_id=130007852588&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007852588&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • 肺血栓塞栓症を合併し、奇異性塞栓による後脊髄動脈症候群を呈した潰瘍性大腸炎の56歳女性例

    荻根沢 真也, 上村 昌寛, 大津 裕, 徳武 孝允, 金澤 雅人, 小野寺 理

    臨床神経学   60 ( 5 )   367 - 367   2020年5月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • Role of RNF213 p.4810K variant in the development of intracranial arterial disease in patients treated with nilotinib 国際誌

    Masahiro Uemura, Masato Kanazawa, Takuma Yamagishi, Takahiro Nagai, Mami Takahashi, Shingo Koide, Masayoshi Tada, Junsuke Shimbo, Aiko Isami, Kunihiko Makino, Masayoshi Masuko, Kouji Nikkuni, Kouichirou Okamoto, Shuichi Igarashi, Kenichi Morita, Osamu Onodera

    Journal of the Neurological Sciences   408   116577 - 116577   2020年1月

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  • Hemorrhagic cerebral small vessel disease caused by a novel mutation in 3′ UTR of collagen type IV alpha 1 国際誌

    Naoko Sakai, Masahiro Uemura, Taisuke Kato, Hiroaki Nozaki, Akihide Koyama, Shouichirou Ando, Hiroyuki Kamei, Motohiro Kato, Osamu Onodera

    Neurology: Genetics   6 ( 1 )   e383   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1212/NXG.0000000000000383

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  • Dural arteriovenous fistula causing complex visual hallucinations without an anopsia

    Shingo Koide, Masahiro Hatakeyama, Masahiro Uemura, Bumpei Kikuchi, Hitoshi Hasegawa, Osamu Onodera

    Clinical Neurology   60 ( 6 )   425 - 428   2020年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    We report the case of a 76-year-old woman who presented with recurrent episodes of complex visual hallucinations in her right visual field without an anopsia. The electroencephalogram showed sharp transients in the left parietotemporal region with phase reversals at T5 and P3. FLAIR MRI revealed hyperintense lesions in the left temporo-occipital lobe, located mainly in the left inferior temporal lobe. Cerebral angiography revealed an arteriovenous shunt from the left occipital artery to the left transverse sinus with cortical venous reflux. The complex visual hallucinations were resolved after transarterial embolization. We therefore hypothesize that this patient's complex visual hallucinations were caused by epileptic seizures or changes in cortical blood flow caused by the cortical venous reflux from the arteriovenous fistula. In general, epileptic hallucinations expand into the bilateral visual field. We reveal that in rare cases, complex visual hallucinations can also be limited to the unilateral visual field without an anopsia. Additionally, we reveal that a dural arteriovenous fistula can cause visual hallucinations without hemianopia.

    DOI: 10.5692/clinicalneurol.60.cn-001371

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  • 外科的介入を受けていない症候性もやもや病の1剖検例

    齋藤 祥二, 齋藤 理恵, 中原 亜紗, 長谷川 仁, 田口 貴博, 上村 昌寛, 本多 忠幸, 伊藤 靖, 小野寺 理, 梅津 哉, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌   133 ( 11-12 )   389 - 389   2019年12月

  • 外科的介入を受けていない症候性もやもや病の1剖検例

    齋藤 祥二, 齋藤 理恵, 中原 亜紗, 長谷川 仁, 田口 貴博, 上村 昌寛, 本多 忠幸, 伊藤 靖, 小野寺 理, 梅津 哉, 藤井 幸彦, 柿田 明美

    新潟医学会雑誌   133 ( 11-12 )   389 - 389   2019年12月

  • Type IV collagen α1の3'UTRの新規変異による脳小血管病

    酒井 直子, 上村 昌寛, 加藤 泰介, 安藤 昭一朗, 野崎 洋明, 亀井 博之, 加藤 元博, 小野寺 理

    臨床神経学   59 ( Suppl. )   S327 - S327   2019年11月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 【脳の自浄システムとしてのアストロサイトとglymphaticシステム】神経脳小血管単位による排泄機構と疾病との関係

    安藤 昭一朗, 上村 昌寛, 小野寺 理

    Dementia Japan   33 ( 3 )   257 - 262   2019年9月

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    記述言語:日本語   出版者・発行元:(一社)日本認知症学会  

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  • 視野欠損を伴わず右視野に限局する複雑幻視を呈した硬膜動静脈瘻の1例

    畠山 公大, 小出 眞悟, 上村 昌寛, 菊池 文平, 長谷川 仁, 藤井 幸彦, 小野寺 理

    日本神経心理学会総会プログラム・予稿集   43回   86 - 86   2019年7月

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    記述言語:日本語   出版者・発行元:日本神経心理学会  

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  • 【指定難病ペディア2019】個別の指定難病 神経・筋系 皮質下梗塞と白質脳症を伴う常染色体優性脳動脈症(CADASIL)[指定難病124]

    上村 昌寛, 小野寺 理

    日本医師会雑誌   148 ( 特別1 )   S111 - S111   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本医師会  

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  • 眼筋症状のみで経過し、発症から8年後に初めて球麻痺症状を呈した抗MuSK抗体陽性重症筋無力症の76歳女性

    北原 匠, 上村 昌寛, 熊谷 航一郎, 柳村 文寛, 中村 航世, 茂木 崇秀, 河内 泉, 小野寺 理

    臨床神経学   59 ( 5 )   305 - 305   2019年5月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 【脳血管障害の最近の進歩】単一遺伝子異常による脳小血管病

    酒井 直子, 上村 昌寛, 小野寺 理

    Medical Science Digest   45 ( 3 )   165 - 168   2019年3月

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    記述言語:日本語   出版者・発行元:(株)ニュー・サイエンス社  

    脳小血管病とは穿通枝動脈、毛細血管などの病変により生じる神経疾患の総称である。脳小血管病では神経活動に応じた血流供給に支障をきたし、認知症などの原因となると推定される。脳小血管病の分子病態はまだ不明な点が多い。近年、複数の遺伝性脳小血管病が報告され、これらの疾患の解析を通じて、分子病態が解明され、新たな治療法の開発に繋がることが期待されている。本稿では遺伝性脳小血管病の代表的疾患であるCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephatopathy(CADASIL)とCerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephatopathy(CARASIL)について概説する。(著者抄録)

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  • 医学と医療の最前線 Glymphatic systemと脳小血管機能不全

    上村 昌寛, 小野寺 理

    日本内科学会雑誌   108 ( 3 )   582 - 586   2019年3月

  • HTRA1 mutations identified in symptomatic carriers have the property of interfering the trimer-dependent activation cascade 国際誌

    Masahiro Uemura, Hiroaki Nozaki, Akihide Koyama, Naoko Sakai, Shoichiro Ando, Masato Kanazawa, Taisuke Kato, Osamu Onodera

    Frontiers in Neurology   10 ( JUN )   693 - 693   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for HTRA1 mutations are asymptomatic, but more than 10 mutations have been reported in symptomatic carriers. The molecular differences between the mutations identified in symptomatic carriers and mutations identified only in CARASIL patients are unclear. HTRA1 is a serine protease that forms homotrimers, with each HTRA1 subunit activating the adjacent HTRA1 via the sensor domain of loop 3 (L3) and the activation domain of loop D (LD). Previously, we analyzed four HTRA1 mutant proteins identified in symptomatic carriers and found that they were unable to form trimers or had mutations in the LD or L3 domain. The mutant HTRA1s with these properties are presumed to inhibit trimer-dependent activation cascade. Indeed, these mutant HTRA1s inhibited wild-type (WT) protease activity. In this study, we further analyzed 15 missense HTRA1s to clarify the molecular character of mutant HTRA1s identified in symptomatic carriers. Methods: We analyzed 12 missense HTRA1s identified in symptomatic carriers (hetero-HTRA1) and three missense HTRA1s found only in CARASIL (CARASIL-HTRA1). The protease activity of the purified recombinant mutant HTRA1s was measured using fluorescein isothiocyanate-labeled casein as substrate. Oligomeric structure was evaluated by size-exclusion chromatography. The protease activities of mixtures of WT with each mutant HTRA1 were also measured. Results: Five hetero-HTRA1s had normal protease activity and were excluded from further analysis. Four of the seven hetero-HTRA1s and one of the three CARASIL-HTRA1s were unable to form trimers. The other three hetero-HTRA1s had mutations in the LD domain. Together with our previous work, 10 of 11 hetero-HTRA1s and two of six CARASIL-HTRA1s were either defective in trimerization or had mutations in the LD or L3 domain (P = 0.006). By contrast, eight of 11 hetero-HTRA1s and two of six CARASIL-HTRA1 inhibited WT protease activity (P = 0.162). Conclusions: HTRA1 mutations identified in symptomatic carriers have the property of interfering the trimer-dependent activation cascade of HTRA1.

    DOI: 10.3389/fneur.2019.00693

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  • 脳小血管病患者でヘテロ接合性に認められたhigh-temperature requirement A serine peptidase 1(HTRA1)変異の病的意義の検討

    上村 昌寛, 小野寺 理

    新潟医学会雑誌   132 ( 3 )   105 - 114   2018年3月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    High-temperature requirement A serine peptidase 1(HTRA1)変異のホモもしくは複合ヘテロ接合体は遺伝性脳小血管病をおこす。一方、近年、脳小血管病患者においてHTRA1変異のヘテロ接合体が複数例報告された。HTRA1はセリンプロテアーゼであり、3量体となる事でその活性を調節している。筆者らは、HTRA1変異ヘテロ接合体で認められたHTRA1変異の病態機序として、変異型HTRA1が優性阻害効果(dominant negative effects:DN)を示すことを提唱してきた。本研究では、既報の変異型HTRA1のDNの有無を解析し、本仮設を検証した。まず、既報の15種(S121R、A123S、R133G、R166C、R166L、A173P、A173T、S284G、S284R、P285Q、F286V、G295R、A321T、L364P、D450H)の変異型HTRA1の精製蛋白を作成し、カゼインを基質としてプロテアーゼ活性を測定した。その結果、11種(S121R、R166C、R166L、A173P、A173T、S284R、P285Q、F286V、G295R、A321T、L364P)で、野生型HTRA1と比較して有意な低下を認めた。次に、野生型HTRA1と変異型HTRA1を混合しプロテアーゼ活性を測定したところ、5種(R166L、A173P、A173T、S284R、G295R)でDNを認めた。さらに、ゲル濾過クロマトグラフィーにて3量体形成能を解析したところ、DNを認める5種の変異のうち、4種(R166L、A173P、A173T、G295R)の3量体の形成不全を認めた。最後にDNを認めたヘテロ接合体変異例17例とDNを認めないヘテロ接合体変異例9例の臨床像を比較したところ、DNを認める群で症候性脳小血管病の頻度が有意に高かった(76.5% vs 33.3%、p<0.046)。以上の結果から、DNを認める変異型HTRA1は、ヘテロ接合体で症候性脳小血管病の発症に寄与するという仮説が支持された。(著者抄録)

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  • CARASIL families from India with 3 novel null mutations in the HTRA1 gene. 国際誌

    Veeramani Preethish-Kumar, Hiroaki Nozaki, Sarbesh Tiwari, Seena Vengalil, Maya Bhat, Chandrajit Prasad, Osamu Onodera, Masahiro Uemura, Seshagiri Doniparthi, Jitender Saini, Saraswati Nashi, Kiran Polavarapu, Atchayaram Nalini

    Neurology   89 ( 23 )   2392 - 2394   2017年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1212/WNL.0000000000004710

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  • Clinical/scientific notes

    Veeramani Preethish-Kumar, Hiroaki Nozaki, Sarbesh Tiwari, Seena Vengalil, Maya Bhat, Chandrajit Prasad, Osamu Onodera, Masahiro Uemura, Seshagiri Doniparthi, Jitender Saini, Saraswati Nashi, Kiran Polavarapu, Atchayaram Nalini

    Neurology   89 ( 23 )   2392 - 2394   2017年12月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1212/WNL.0000000000004710

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  • 家族性脳小血管病患者で報告された変異型HTRA1蛋白質の機能解析

    上村 昌寛, 野崎 洋明, 加藤 泰介, 小山 哲秀, 小野寺 理

    生命科学系学会合同年次大会   2017年度   [1P - 1241]   2017年12月

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    記述言語:英語   出版者・発行元:生命科学系学会合同年次大会運営事務局  

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  • 【CADASILとCARASIL】CARASILの臨床遺伝学的特徴と分子病態

    酒井 直子, 野崎 洋明, 上村 昌寛, 小野寺 理

    神経内科   87 ( 6 )   638 - 642   2017年12月

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • Visualization of the Intimal Flap in Intracranial Arterial Dissection Using High-Resolution 3T MRI 国際誌

    Masahiro Uemura, Kenshi Terajima, Yuji Suzuki, Masaki Watanabe, Yasuhisa Akaiwa, Shinichi Katada, Kouichirou Okamoto, Masatoyo Nishizawa, Hironaka Igarashi, Tsutomu Nakada

    Journal of Neuroimaging   27 ( 1 )   29 - 32   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND PURPOSE: Presence of an intimal flap is a critical imaging finding in diagnosing intracranial artery dissection (ICAD). Recent reports showed that high-resolution magnetic resonance imaging (MRI) was better at identifying intimal flaps as compared with routine MRI techniques used in clinical settings. However, no current standardized sequence for high-resolution MRI without gadolinium enhancement produces images of satisfactory quality with clinically tolerable scanning times. This study evaluated a nonenhanced high-resolution fast spin echo (HR-FSE) MRI sequence for visualizing intimal flaps in patients with ICAD. SUBJECTS AND METHODS: Three patients with ICAD underwent plain MRI examination using a 2-dimensional T2-weighted FSE imaging sequence optimized for our 3T system (in-plane pixel size,.23 mm ×.23 mm; slice thickness 3 mm with no interslice gap), as well as scanning with conventional modalities, including CT angiography, magnetic resonance angiography, and digital subtraction angiography. We assessed whether these imaging methods could visualize an intimal flap and/or double lumen sign in the participants and compared the results between HR-FSE and the other modalities. RESULTS: HR-FSE images clearly showed intimal flaps and double lumen signs in all 3 patients, whereas the conventional modalities identified a double lumen sign in only 2 of the 3 patients. CONCLUSIONS: The present method of optimized HR-FSE imaging with a 3T system improved visualization of intimal flaps and should thus be considered for assessing patients with suspected ICAD that cannot be definitively diagnosed by conventional imaging modalities.

    DOI: 10.1111/jon.12380

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  • Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)

    Masahiro Uemura, Hiroaki Nozaki, Osamu Onodera

    Brain and Nerve   69 ( 1 )   25 - 33   2017年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Cerebral small vessel disease (CSVD) is frequently observed among the elderly and is known to cause dementia and gait disturbance associated with white matter lesions, lacunar infarcts, and cerebral hemorrhage. Molecular mechanistic studies promise to provide new insights into the pathogenesis of hereditary CSVD. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is one of the hereditary CSVDs caused by a mutation in the hightemperature requirement serine peptidase A1 (HTRA1) gene. The loss of HTRA1 protease activity increases signaling via transforming growth factor (TGF)β, thereby resulting in CARASIL. Although the CARASIL has been characterized by juvenile onset alopecia and spondylosis deformans, these features are not always observed in individuals with an HTRA1 mutation. Moreover, some HTRA1 mutations cause CSVD in heterozygous states. Therefore, the clinical features of CSVD resulting from an HTRA1 mutation extend to patients with CSVD alone or to those with dominantly inherited CSVD.

    DOI: 10.11477/mf.1416200631

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  • Cerebral venous sinus thrombosis due to oral contraceptive use: Postmortem 3 T-MRI and autopsy findings

    Masahiro Uemura, Yoshihiro Tsukamoto, Yasuhisa Akaiwa, Masaki Watanabe, Ayako Tazawa, Sou Kasahara, Minoru Endou, Ryosuke Ogura, Kouichirou Okamoto, Yukihiko Fujii, Tsutomu Nakada, Akiyoshi Kakita, Masatoyo Nishizawa

    Human Pathology: Case Reports   6   32 - 36   2016年12月

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    掲載種別:研究論文(学術雑誌)  

    Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke, and mortality of the acute phase is high. We report the clinical, postmortem 3 T-MRI, and autopsy features of a patient, 20-year-old Japanese woman, with CVST who died shortly after starting to use low-dose estrogen combined hormonal contraceptives (CHCs). A postmortem 3 T-MRI study with our originally developed system revealed abnormal intensities suggestive of thrombi extending throughout the straight sinus and left sigmoid sinus. At autopsy, in accordance with the images, we performed careful preparations of the sinuses. Histological examination revealed an organizing white thrombus occupying the lumen of the left sigmoid sinus, and an acute, red thrombus in the lumen of the left transverse, straight, and tentorial sinuses, and vein of Galen, indicating that the thrombus had developed first in the left sigmoid sinus, then extended retrogradely to the more proximal portion of the sinus system, reaching the vein of Galen. The features of the present CVST patient appear to be informative, when encountering CHC users with neurological symptoms, even in those who begun to use low-dose estrogen CHCs only recently.

    DOI: 10.1016/j.ehpc.2016.01.002

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  • Ipsilateral hemiparesis in lateral medullary infarction: Clinical investigation of the lesion location on magnetic resonance imaging 国際誌

    Masahiro Uemura, Hiroaki Naritomi, Hisakazu Uno, Arisa Umesaki, Kotaro Miyashita, Kazunori Toyoda, Kazuo Minematsu, Kazuyuki Nagatsuka

    Journal of the Neurological Sciences   365   40 - 45   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background In 1946, Opalski reported two cases of Wallenberg syndrome with ipsilateral hemiparesis (IH). His hypothesis seems to be based on the view that IH is caused by post-decussating pyramidal tract damage. Afterwards, other researchers proposed a different hypothesis that ipsilateral sensory symptoms of limbs (ISSL) or ipsilateral limb ataxia (ILA) caused by lateral medullary infarction (LMI) might lead to ipsilateral motor weakness. The present study is aimed to clarify whether IH in LMI patients is attributable mainly to ISSL/ILA or disruption of ipsilateral post-decussating pyramidal tract. Methods Thirty-two patients with acute LMI admitted during the last 13 years were divided to IH Group (n = 7) and Non-IH Group (n = 25). Lesion location/distribution on MRI and neurological findings were compared between the two groups. Results LMI involved the lower medulla in all seven IH patients and 12 of 25 Non-IH patients. The lower medullary lesion extended to the cervico-medullary junction (CMJ) in four of seven IH patients and one of 12 Non-IH patients. Definitive extension to upper cervical cord (UCC) was confirmed in none of the patients. ISSL was found in two IH and three Non-IH patients all showing only superficial sensory impairments. ILA or hypotonia was observed in 57% of IH and 60% of Non-IH patients. Conclusion IH in LMI appears to be due mainly to post-decussating pyramidal tract damage at the lower medulla instead of ILA or ISSL participation.

    DOI: 10.1016/j.jns.2016.04.006

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  • Distinct molecular mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL 国際誌

    Hiroaki Nozaki, Taisuke Kato, Megumi Nihonmatsu, Yohei Saito, Ikuko Mizuta, Tomoko Noda, Ryoko Koike, Kazuhide Miyazaki, Muichi Kaito, Shoichi Ito, Masahiro Makino, Akihide Koyama, Atsushi Shiga, Masahiro Uemura, Yumi Sekine, Ayuka Murakami, Suzuko Moritani, Kenju Hara, Akio Yokoseki, Ryozo Kuwano, Naoto Endo, Takeshi Momotsu, Mari Yoshida, Masatoyo Nishizawa, Toshiki Mizuno, Osamu Onodera

    Neurology   86 ( 21 )   1964 - 1974   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: To elucidate the molecular mechanism of mutant HTRA1-dependent cerebral small vessel disease in heterozygous individuals. Methods: We recruited 113 unrelated index patients with clinically diagnosed cerebral small vessel disease. The coding sequences of the HTRA1 gene were analyzed. We evaluated HTRA1 protease activities using casein assays and oligomeric HTRA1 formation using gel filtration chromatography. Results: We found 4 heterozygous missense mutations in the HTRA1 gene (p.G283E, p.P285L, p.R302Q, and p.T319I) in 6 patients from 113 unrelated index patients and in 2 siblings in 2 unrelated families with p.R302Q. The mean age at cognitive impairment onset was 51.1 years. Spondylosis deformans was observed in all cases, whereas alopecia was observed in 3 cases; an autopsied case with p.G283E showed arteriopathy in their cerebral small arteries. These mutant HTRA1s showed markedly decreased protease activities and inhibited wild-type HTRA1 activity, whereas 2 of 3 mutant HTRA1s reported in cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (A252T and V297M) did not inhibit wild-type HTRA1 activity. Wild-type HTRA1 forms trimers; however, G283E and T319I HTRA1, observed in manifesting heterozygotes, did not form trimers. P285L and R302Q HTRA1s formed trimers, but their mutations were located in domains that are important for trimer-associated HTRA1 activation; in contrast, A252T and V297M HTRA1s, which have been observed in CARASIL, also formed trimers but had mutations outside the domains important for trimer-associated HTRA1 activation. Conclusions: The mutant HTRA1s observed in manifesting heterozygotes might result in an impaired HTRA1 activation cascade of HTRA1 or be unable to form stable trimers.

    DOI: 10.1212/WNL.0000000000002694

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  • 【認知症】病態生理 周皮細胞と認知症

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    最新医学   71 ( 3月増刊 )   544 - 549   2016年3月

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    記述言語:日本語   出版者・発行元:(株)最新医学社  

    周皮細胞は主に毛細血管レベルに分布し,微小循環の調節に重要な役割を持つ細胞の1つである.近年,周皮細胞が血液脳関門(BBB)の維持や脳血流調節に関与しており,その機能低下が認知症の病態に影響を及ぼす可能性が指摘されている.このことは,周皮細胞機能の維持や改善が,認知症治療の新たな標的と成りうることを示唆している.本稿では,最近の知見を交えながら,周皮細胞の機能や認知症病態との関連について述べる.(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J00516&link_issn=&doc_id=20160407220009&doc_link_id=issn%3D0370-8241%26volume%3D71%26issue%3D3%26spage%3D544&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0370-8241%26volume%3D71%26issue%3D3%26spage%3D544&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

  • 3T-MRIを用いた頭蓋内血管異常の臨床的検討

    上村 昌寛, 寺島 健史, 鈴木 雄治, 二宮 格, 赤岩 靖久, 五十嵐 博中, 中田 力, 西澤 正豊

    臨床神経学   55 ( Suppl. )   S414 - S414   2015年12月

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    記述言語:日本語   出版者・発行元:(一社)日本神経学会  

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  • 【脳血管からみた認知症の病態】脳の微小循環維持シグナルと血管性認知症 CARASILからのアプローチ

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    Dementia Japan   29 ( 4 )   534 - 540   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本認知症学会  

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  • 【最新臨床脳卒中学[下]-最新の診断と治療-】血管性認知症 遺伝性血管性認知症の診断と治療 CADASILとCARASILについて

    上村 昌寛, 野崎 洋明, 西澤 正豊, 小野寺 理

    日本臨床   72 ( 増刊7 最新臨床脳卒中学(下) )   619 - 623   2014年10月

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    記述言語:日本語   出版者・発行元:(株)日本臨床社  

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  • Spontaneous middle cerebral artery dissection demonstrated by high-resolution t1-weighted 3d image 国際誌

    Masahiro Uemura, Yasuhisa Akaiwa, Masafumi Toriyabe, Takuya Mashima, Kenshi Terajima, Takayoshi Shimohata, Hironaka Igarashi, Tsutomu Nakada, Masatoyo Nishizawa

    Cerebrovascular Diseases   36 ( 3 )   243 - 244   2013年10月

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  • Dropped head syndrome in amyotrophic lateral sclerosis 国際誌

    Masahiro Uemura, Takayuki Kosaka, Takayoshi Shimohata, Masanori Ishikawa, Yasushi Nishihira, Yasuko Toyoshima, Kaori Yanagawa, Izumi Kawachi, Hitoshi Takahashi, Masatoyo Nishizawa

    Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration   14 ( 3 )   232 - 233   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3109/17482968.2012.727424

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  • Cell-based therapy to promote angiogenesis in the brain following ischemic damage 国際誌

    Masahiro Uemura, Yukiko Kasahara, Kazuyuki Nagatsuka, Akihiko Taguchi

    Current Vascular Pharmacology   10 ( 3 )   285 - 288   2012年5月

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    記述言語:英語  

    Cell-based therapies are a novel approach for regeneration of microvasculature. We have shown that administration of CD34-positive cells, the rich cell fraction of endothelial progenitor cells, after stroke induces angiogenesis that results in enhanced endogenous neurogenesis and functional recovery in a murine model. Moreover, injury-induced neurogenesis occurs in the human brain following a stroke during the acute to sub-acute period. Based on these observations, clinical trials of cell therapies that aim to regenerate micro-circulation in the brain following a stroke are ongoing worldwide. This review summarizes the current basic research findings about the link between angiogenesis and neurogenesis in the post-stroke brain and introduces the ongoing clinical trials of cell-based therapies for patients that have suffered a stroke. © 2012 Bentham Science Publishers.

    DOI: 10.2174/157016112799959369

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  • Identification of internal carotid artery dissection by transoral carotid ultrasonography 国際誌

    Rieko Suzuki, Masatoshi Koga, Kazunori Toyoda, Masahiro Uemura, Hikaru Nagasawa, Yusuke Yakushiji, Hiroshi Moriwaki, Naoaki Yamada, Kazuo Minematsu

    Cerebrovascular Diseases   33 ( 4 )   369 - 377   2012年4月

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    記述言語:英語  

    Background and Purpose: Conventional transsurface carotid ultrasonography (TSCU) via the cervical surface often fails to detect dissection of the extracranial internal carotid artery (ICA). The role of transoral carotid ultrasonography (TOCU) in the detection of ICA dissection was examined. Method: Patients with unilateral extracranial ICA dissection identified by digital subtraction angiography (DSA) from our database of patients with ischemic stroke or transient ischemic attack (TIA) were reviewed. Findings of dissection were compared between TSCU and TOCU. Results: Eight patients (7 men, 37-69 years old), including 7 with ischemic stroke and 1 with TIA, had ICA dissection. By DSA, dissection was identified between the first and third vertebrae in 4 patients and from the third cervical vertebra to the intracranial level in the remaining 4. TOCU images revealed an intimal flap as definite evidence of dissection in all patients. In 7 patients, color flow signals were not seen in false lumens, indicating thrombosed lumens. Four patients showed morphological changes of dissection on follow-up TOCU, including a patient with recovery of color flow signals in false lumens. The diameter of the dissected ICA was 7.3 ± 0.7 mm and that of the contralateral ICA was 4.9 ± 0.6 mm (p = 0.008). In contrast, TSCU did not enable any conclusive findings of ICA dissection to be made in any patient. Six patients had intramural hematoma on T -weighted MRI, and 2 had an intimal flap with a double lumen on magnetic resonance angiography. Conclusion: TOCU has advantages over TSCU in achieving an accurate diagnosis and follow-up evaluation of ICA dissection. © 2012 S. Karger AG, Basel. 1

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MISC

  • Frequencies of Hereditary Cerebral Small Vessel Diseases Among Patients With Adult-Onset Leukoencephalopathy

    Masahiro Uemura, Hiroaki Nozaki, Naoko Sakai, Shouichirou Ando, Masato Kanazawa, Hajime Kondo, Akira Iwanaga, Hiroyuki Murota, Takeshi Ikeuchi, Ikuko Mizuta, Toshiki Mizuno, Osamu Onodera

    STROKE   51   2020年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Characteristic Brain MRI Features of Manifesting Heterozygotes With Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

    Masahiro Uemura, Hiroaki Nozaki, Yumi Sekine, Ikuko Mizuta, Tomoko Noda, Kazuhide Miyazaki, Muichi Kaito, Yoshinori Nishimoto, Yutaka Shimoe, Akiko Shirata, Kiyomi Yamane, Sohei Yanagawa, Mikio Hirayama, Masato Tamura, Toshiki Mizuno, Masatoyo Nishizawa, Osamu Onodera

    STROKE   48   2017年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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