研究者詳細 - 小野寺　理

論文 - 小野寺　理

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Early diagnosis of cryptococcal meningoencephalitis in HIV-negative patients: Integration of brain MRI and clinical findings. 国際誌

Kosei Nakamura, Masato Kanazawa, Yuka Koike, Takuya Konno, Osamu Onodera

eNeurologicalSci 38 100552 - 100552 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: Cryptococcal meningoencephalitis (CM) in human immunodeficiency virus (HIV)-negative patients are often diagnosed later than in HIV-infected patients, which increases mortality rates concerning the former. Consequently, early diagnosis and treatment are crucial for improving clinical prognosis in HIV-negative patients. This study investigated the utility of magnetic resonance imaging (MRI) in combination with clinical and laboratory findings for early diagnosis of CM in HIV-negative patients. METHODS: This retrospective cohort analysis included consecutive patients diagnosed with central nervous system (CNS) infections. Demographic profiles, laboratory findings, admission symptoms, and MRI findings were assessed. A comparative analysis between CM and other CNS infections was performed. RESULTS: Twelve HIV-negative patients were diagnosed with CM, while 38 exhibited other CNS infections (two fungal, 23 bacterial, 12 viral, one parasitic). Pseudocysts on MRI (p = 0.002), absence of fever (p = 0.001), headache (p = 0.005), and normal C-reactive protein (CRP) levels (p = 0.020) were specific findings in CM. By applying a cut-off value of one point in combination of pseudocysts, absence of fever, headache, and normal CRP levels in differentiating CM from other CNS infections, the sensitivity and specificity were calculated as 76.3 % and 91.7 %, respectively. CONCLUSION: Integrating pseudocysts, absence of fever, headache, and normal CRP levels predicts early CM diagnosis, potentially improving outcomes.

DOI： 10.1016/j.ensci.2025.100552

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Novel Aspects of Hereditary Spastic Paraplegia: A Clinicopathologic and Biochemical Study of a Patient With a Heterozygous GCH1 Variant. 国際誌

Shoko Hongo, Tetsuhiko Ikeda, Mari Tada, Rina Aida, Tetsuo Ozawa, Norikazu Hara, Akinori Miyashita, Takashi Nakajima, Osamu Onodera, Takeshi Ikeuchi, Hiroshi Ichinose, Akiyoshi Kakita

Neuropathology and applied neurobiology 51 ( 1 ) e70006 2025年2月

A case of cerebral amyloid angiopathy with ipsilateral tau and contralateral amyloid PET uptake related to cadaveric dura mater implanted in childhood

Yuki Hatakeyama, Atsushi Michael Kimura, Shintaro Tsuboguchi, Mikhail Ratanov, Kosei Nakamura, Masahiro Hatakeyama, Yukimi Nakamura, Masaki Watanabe, Yoshihiro Murakami, Yuko Saito, Shigeo Murayama, Kensaku Kasuga, Takeshi Ikeuchi, Hironaka Igarashi, Osamu Onodera, Hitoshi Shimada

European Journal of Nuclear Medicine and Molecular Imaging 2024年12月

Blood–brain barrier dysfunction in multiple system atrophy: A human postmortem study

Ramil Gabdulkhaev, Hiroshi Shimizu, Masato Kanazawa, Yasuko Kuroha, Arika Hasegawa, Jiro Idezuka, Kazuki Tainaka, Osamu Onodera, Akiyoshi Kakita

Neuropathology 2024年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by an accumulation of phosphorylated α‐synuclein (p‐αsyn) in oligodendrocytes in the form of glial cytoplasmic inclusions (GCIs). In MSA, not only mature oligodendrocytes but also oligodendrocyte precursor cells (OPCs) are affected. The latter play an important role in remyelination by differentiating into mature oligodendrocytes, as well as maintaining the blood–brain barrier (BBB) by promoting the expression of tight junction proteins. We have hypothesized that in MSA, the BBB is impaired as a result of aberrant interactions between affected OPCs and the cerebral vasculature. To verify this hypothesis, we conducted a neuropathological examination of postmortem brains from MSA patients and control subjects, focusing on the primary motor area, one of the main regions affected in MSA. Using double immunofluorescence, we quantified the expression of tight junction protein claudin‐5 in capillary endothelial cells and found that it was significantly lower in MSA than in controls in both the gray matter and white matter. Furthermore, a significantly higher amount of fibrinogen was extravasated into the brain parenchyma in MSA patients than in controls. In addition, leakage of IgG was detected almost specifically in MSA brain parenchyma, as visualized in three dimensions by combining techniques of chemical tissue clearing and light sheet microscopy. Finally, we confirmed accumulation of p‐αsyn‐positive GCIs along the cerebral vasculature within OPCs. These results suggest that BBB dysfunction and associated fibrinogen extravasation are constant findings in MSA, presumably triggered by the deposition of p‐αsyn in perivascular OPCs.

DOI： 10.1111/neup.13021

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SMN2 gene copy number affects the incidence and prognosis of motor neuron diseases in Japan

Tomohiko Ishihara, Akihide Koyama, Naoki Atsuta, Mari Tada, Saori Toyoda, Kenta Kashiwagi, Sachiko Hirokawa, Yuya Hatano, Akio Yokoseki, Ryoichi Nakamura, Genki Tohnai, Yuishin Izumi, Ryuji Kaji, Mitsuya Morita, Asako Tamura, Osamu Kano, Masashi Aoki, Satoshi Kuwabara, Akiyoshi Kakita, Gen Sobue, Osamu Onodera

BMC Medical Genomics 17 ( 1 ) 2024年11月

L-arginine in patients with spinocerebellar ataxia type 6: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

Tomohiko Ishihara, Masayoshi Tada, Yoshitomi Kanemitsu, Yuji Takahashi, Kinya Ishikawa, Kensuke Ikenaka, Makito Hirano, Takanori Yokota, Eiko N. Minakawa, Katsuhisa Saito, Yoshitaka Nagai, Osamu Onodera

eClinicalMedicine 102952 - 102952 2024年11月

A case of isolated dystextia due to subcortical infarction: a novel condition of digital device era

Masahiro Hatakeyama, Takeshi Kanayama, Saori Tokunaga, Toshiya Kizaki, Shintaro Tsuboguchi, Masato Kanazawa, Osamu Onodera

BMC Neurology 24 ( 1 ) 2024年10月

本邦における抗LGI1脳炎の特徴自己免疫介在性脳炎・脳症の全国疫学調査

河内泉, 佐治越爾, 佐藤泰憲, 飯塚高浩, 木村暁夫, 佐久間啓, 中嶋秀人, 大石真莉子, 中島章博, 神田隆, 高橋幸利, 渡邊修, 鵜沢顕之, 桑原聡, 小野寺理

臨床神経学 64 ( Suppl. ) S252 - S252 2024年10月

本邦における抗NMDA受容体脳炎の特徴自己免疫介在性脳炎・脳症の全国疫学調査

佐治越爾, 佐藤泰憲, 飯塚高浩, 木村暁夫, 佐久間啓, 中嶋秀人, 大石真莉子, 中島章博, 神田隆, 高橋幸利, 渡邊修, 鵜沢顕之, 桑原聡, 小野寺理, 河内泉

臨床神経学 64 ( Suppl. ) S252 - S252 2024年10月

Qki5 safeguards spinal motor neuron function by defining the motor neuron-specific transcriptome via pre-mRNA processing. 国際誌

Yoshika Hayakawa-Yano, Takako Furukawa, Tsuyoshi Matsuo, Takahisa Ogasawara, Masahiro Nogami, Kazumasa Yokoyama, Masato Yugami, Munehisa Shinozaki, Chihiro Nakamoto, Kenji Sakimura, Akihide Koyama, Kazuhiro Ogi, Osamu Onodera, Hirohide Takebayashi, Hideyuki Okano, Masato Yano

Proceedings of the National Academy of Sciences of the United States of America 121 ( 37 ) e2401531121 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Many RNA-binding proteins (RBPs) are linked to the dysregulation of RNA metabolism in motor neuron diseases (MNDs). However, the molecular mechanisms underlying MN vulnerability have yet to be elucidated. Here, we found that such an RBP, Quaking5 (Qki5), contributes to formation of the MN-specific transcriptome profile, termed "MN-ness," through the posttranscriptional network and maintenance of the mature MNs. Immunohistochemical analysis and single-cell RNA sequencing (scRNA-seq) revealed that Qki5 is predominantly expressed in MNs, but not in other neuronal populations of the spinal cord. Furthermore, comprehensive RNA sequencing (RNA-seq) analyses revealed that Qki5-dependent RNA regulation plays a pivotal role in generating the MN-specific transcriptome through pre-messenger ribonucleic acid (mRNA) splicing for the synapse-related molecules and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathways. Indeed, MN-specific ablation of the Qki5 caused neurodegeneration in postnatal mice and loss of Qki5 function resulted in the aberrant activation of stress-responsive JNK/SAPK pathway both in vitro and in vivo. These data suggested that Qki5 plays a crucial biological role in RNA regulation and safeguarding of MNs and might be associated with pathogenesis of MNDs.

DOI： 10.1073/pnas.2401531121

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Lessons from the ATTeST trial in ataxia telangiectasia. 国際誌

Yuka Koike, Osamu Onodera

The Lancet. Neurology 23 ( 9 ) 846 - 847 2024年9月

Indications for a brain biopsy in neurological diseases of unknown etiology: The role of magnetic resonance imaging findings and liquid biopsy in yielding definitive pathological diagnoses. 国際誌

Toshiya Kizaki, Masato Kanazawa, Takanobu Ishiguro, Manabu Natsumeda, Mari Tada, Hiroshi Shimizu, Kouichirou Okamoto, Makoto Oishi, Akiyoshi Kakita, Yukihiko Fujii, Osamu Onodera

Journal of the neurological sciences 463 123150 - 123150 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Brain biopsies are often considered for patients who cannot be diagnosed with various laboratory test results. However, physicians tend to be hesitant regarding their application in possibly non-neoplastic brain diseases, due to the invasiveness and risks. The aim was to determine the indications for brain biopsies in cases of neurological diseases of unknown etiology. We retrospectively evaluated diagnostic accuracy, laboratory findings (including a liquid biopsy for malignant lymphoma), magnetic resonance imaging (MRI) characteristics and the post-treatment outcomes of patients undergoing brain biopsies for neurological diseases of unknown etiology. The data of patients who had undergone a brain biopsy during their admission to Niigata University Hospital, between 2011 and 2024, were reviewed. Moreover, the laboratory data and MRI findings between patients with definitive and nonspecific biopsy diagnoses were compared. Twenty-six patients underwent a brain biopsy, and a definitive diagnosis was obtained in 14 patients (53.8%). Even in cases where a nonspecific diagnosis was made, biopsy findings helped rule out malignancy and guide clinical diagnosis and treatment decisions. The liquid biopsy for malignant lymphoma was performed in eight patients, with one yielding a positive result, consistent with primary central nervous system lymphoma. The sensitivity and specificity of liquid biopsy were 0.5 and 1, respectively. Diffusely contrasted cortical lesions and the presence of mass effects on MRI, were significantly associated with a definitive diagnosis, compared to a nonspecific diagnosis. In conclusion, brain MRI and liquid biopsies can assist in determining the appropriate indications for brain biopsies in neurological diseases of unknown etiology.

DOI： 10.1016/j.jns.2024.123150

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A patient with neuronal intranuclear inclusion disease developed encephalitis‐like symptoms after cerebral angiography

Shin Koide, Shintaro Tsuboguchi, Shingo Koide, Itaru Ninomiya, Taiki Saito, Takanobu Ishiguro, Etsuji Saji, Yo Higuchi, Takeshi Ikeuchi, Makoto Oishi, Masato Kanazawa, Osamu Onodera

Neurology and Clinical Neuroscience 2024年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Abstract

Patients with neuronal intranuclear inclusion disease (NIID) can present with encephalitis‐like symptoms such as recurrent paroxysmal fever and unconsciousness. To date, no specific triggers for these symptoms have been reported. In our case, an 78‐year‐old woman became unconscious and developed fever after cerebral angiography. The patient had experienced four episodes of unconsciousness and fever in the past 7 years. Postangiography, she immediately became unconscious and developed fever. No vascular abnormalities were found and magnetic resonance imaging of the brain revealed expanding white matter lesions and hyperintense lesions along the corticomedullary junction. Genetic analysis revealed an abnormal GGC repeat expansion in NOTCH2NLC. Thus, we diagnosed the patient with NIID. We suggest that cerebral angiography is a possible trigger for encephalitis‐like symptoms in NIID.

DOI： 10.1111/ncn3.12839

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Cerebellar compensation: a case of aphasia due to cerebellar hemorrhage

Yukiko Kinoshita, Masahiro Hatakeyama, Mika Otsuki, Takanobu Ishiguro, Etsuji Saji, Masato Kanazawa, Osamu Onodera

Journal of Neurology 2024年6月

UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study

Han Lyu, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kenji Sato, Hiroyuki Kawashima, Osamu Onodera, Ichiei Narita, Koichi Tabeta

Heliyon 10 ( 12 ) e32512 - e32512 2024年6月

造影効果を伴う多発脳病変を呈し,悪性腫瘍との鑑別を要したウイルス性髄膜脳炎の73歳女性の一例

柏木健太, 大津裕, 岸諒太, 福本淳貴, 石黒敬信, 佐治越爾, 金澤雅人, 小野寺理

臨床神経学 64 ( 6 ) 438 - 438 2024年6月

From bench to bedside: US-Japan Collaborative Workshop on the NVU

Cesario Borlongan, Elga Esposito, Laarni Grace Corales, Yorito Hattori, Yu Hayashi, Masafumi Ihara, Jeffrey J. Iliff, Kassandra Kisler, Shinobu Kitazume, Schuichi Koizumi, Jialing Liu, Takakuni Maki, Osamu Onodera, Satoshi Saito, Kazunobu Sawamoto, Kazuhiro Sohya, Akihiko Taguchi, Shinichi Takahashi, Kenji Tanaka, Toshiaki Taoka, Hiroaki Wake, Michisuke Yuzaki

The Journal of Physiological Sciences 74 ( S1 ) 2024年5月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

The joint workshop between U.S. and Japanese researchers, supported by The U.S.–Japan Brain Research Cooperative Program, convened in January 2023 at Keio University Mita campus in Tokyo, Japan. The workshop had a threefold objective. Firstly, it aimed to facilitate robust exchanges between U.S. and Japanese researchers engaged in Neurovascular Unit (NVU) research, enhancing the global network of scholars in the field. Secondly, it aimed to encourage the initiation of collaborative research projects, fostering interdisciplinary efforts and synergistic advancements in understanding the brain vascular physiology and central nervous system. Lastly, the workshop emphasized the nurturing of young researchers, recognizing their pivotal role in shaping the future of NVU research. Throughout the workshop, participants discussed fundamental aspects of the NVU, exploring its complex connections and vital functions. By sharing their expertise and insights, the workshop attendees sought to uncover novel approaches to mitigate the burden of neurological diseases for individuals worldwide. This report provides a summary of the presentations and discussions held during the workshop, showcasing the collective efforts and progress made by the participants.

DOI： 10.1186/s12576-024-00917-4

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その他リンク： https://link.springer.com/article/10.1186/s12576-024-00917-4/fulltext.html

Distal CIDPと鑑別を要したが、M蛋白やVEGFの再検が診断に有用であったPOEMS症候群の一例

鈴木大介, 鈴木佑弥, 菊池謙次, 鈴木義広, 小出伸, 安藤昭一朗, 石黒敬信, 金澤雅人, 小野寺理, 諏訪部達也, 瀧澤淳

臨床神経学 64 ( 5 ) 365 - 365 2024年5月

Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ

Akihiro Nakajima, Fumihiro Yanagimura, Etsuji Saji, Hiroshi Shimizu, Yasuko Toyoshima, Kaori Yanagawa, Musashi Arakawa, Mariko Hokari, Akiko Yokoseki, Takahiro Wakasugi, Kouichirou Okamoto, Hirohide Takebayashi, Chihiro Fujii, Kyoko Itoh, Yo-ichi Takei, Shinji Ohara, Mitsunori Yamada, Hitoshi Takahashi, Masatoyo Nishizawa, Hironaka Igarashi, Akiyoshi Kakita, Osamu Onodera, Izumi Kawachi

Acta Neuropathologica 147 ( 1 ) 2024年4月

Acute respiratory failure caused by brainstem demyelinating lesions in an older patient with an atypical relapsing autoimmune disorder

Shoko Hongo, Hiroshi Shimizu, Etsuji Saji, Akihiro Nakajima, Kouichirou Okamoto, Izumi Kawachi, Osamu Onodera, Akiyoshi Kakita

Neuropathology 2024年4月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

An 84‐year‐old man presented with somnolence, dysphagia, and right hemiplegia, all occurring within a month, approximately one year after initial admission due to subacute, transient cognitive decline suggestive of acute disseminated encephalomyelitis involving the cerebral white matter. Serial magnetic resonance imaging (MRI) studies over that period revealed three high‐intensity signal lesions on fluid‐attenuated inversion recovery images, appearing in chronological order in the left upper and left lower medulla oblongata and left pontine base. Despite some clinical improvement following methylprednisolone pulse therapy, the patient died of respiratory failure. Autopsy revealed four fresh, well‐defined lesions in the brainstem, three of which corresponded to the lesions detected radiologically. The remaining lesion was located in the dorsal medulla oblongata and involved the right solitary nucleus. This might have appeared at a later disease stage, eventually causing respiratory failure. Histologically, all four lesions showed loss of myelin, preservation of axons, and infiltration of lymphocytes, predominantly CD8‐positive T cells, consistent with the histological features of autoimmune demyelinating diseases, particularly the confluent demyelination observed in the early and acute phases of multiple sclerosis (MS). In the cerebral white matter, autoimmune demyelination appeared superimposed on ischemic changes, consistent with the cerebrospinal fluid (CSF) and MRI findings on initial admission. No anti‐AQP4 or MOG antibodies or those potentially causing autoimmune encephalitis/demyelination were detected in either the serum or CSF. Despite several similarities to MS, such as the relapsing–remitting disease course and lesion histology, the entire clinicopathological picture in the present patient, especially the advanced age at onset and development of brainstem lesions in close proximity within a short time frame, did not fit those of MS or other autoimmune diseases that are currently established. The present results suggest that exceptionally older individuals can be affected by an as yet unknown inflammatory demyelinating disease of the CNS.

DOI： 10.1111/neup.12976

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