研究者詳細 - 橋詰　淳

論文 - 橋詰　淳

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Disease mechanism, biomarker and therapeutics for spinal and bulbar muscular atrophy (SBMA). 招待有り査読有り

Hashizume A, Fischbeck KH, Pennuto M, Fratta P, Katsuno M.

J Neurol Neurosurg Psychiatry. 91 巻 ( 10 ) 頁： 123 - 130 2020年10月

Elevated serum creatine kinase in the early stage of sporadic amyotrophic lateral sclerosis. 査読有り

Ito D, Hashizume A, Hijikata Y, Yamada S, Iguchi Y, Iida M, Kishimoto Y, Moriyoshi H, Hirakawa A, Katsuno M.

J Neurol. 266 巻 ( 12 ) 頁： 2952 - 2961 2019年12月

Diffuse but Non-homogeneous Brain Atrophy: Identification of Specific Brain Regions and Their Correlation with Clinical Severity in Rett Syndrome 査読有り Open Access

Narita H., Natsume J., Suzuki T., Shiohama T., Kawaguchi M., Okazaki M., Hashizume A., Naganawa S., Ito Y., Yamamoto H., Nakata T., Kidokoro H., Takahashi Y., Takahashi S., Tsujimura K.

Brain and Development 47 巻 ( 3 ) 頁： 104348 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Brain and Development

Background: Rett syndrome is a genetic neurodevelopmental disorder that predominantly affects girls. While microcephaly is a common feature, there is limited information on the detailed structural changes in the brain. This study aimed to identify regional brain volume abnormalities and explore the correlation between brain volume and clinical characteristics. Methods: We compared the regional brain volumes of 20 female children with Rett syndrome to those of 25 healthy female children. Additionally, we assessed the correlation between regional brain volume, Clinical Severity Scores, and epilepsy status. Results: Significantly smaller volumes were observed in all brain regions, including the cerebral cortex, cerebral white matter, subcortical gray matter, cerebellum, and brainstem. Within the cortical regions, volume reduction was prominent in the left precentral, right lateral occipital, left precuneus, left inferior parietal, and right medial orbitofrontal cortices. After correcting for intracranial volumes, volume reduction was more prominent in the cerebral cortices than in the cerebral white matter. Small volumes were consistently observed, regardless of age. Negative correlations were observed between the volumes of multiple regions and the Clinical Severity Scores. There were no correlations among regional brain volume, seizure control, or duration of epilepsy. Conclusion: The mechanism underlying the cortical-dominant volume reduction remains unclear; however, it may be caused by altered synapse development associated with methyl-CpG-binding protein 2 gene abnormalities. Characteristic impairments in visual recognition and deterioration of motor function in Rett syndrome may be associated with significant volume reduction in specific cortical regions, such as the lateral occipital cortex, precuneus, and precentral gyrus.

DOI： 10.1016/j.braindev.2025.104348

Open Access

Scopus

PubMed

Re-evaluation of blood culture contamination rates: Discordance between clinical and laboratory assessment 査読有り

Hamada, H; Morioka, H; Okazaki, M; Hashizume, A; Kanda, K; Oka, K; Iguchi, M; Yagi, T

JOURNAL OF INFECTION AND CHEMOTHERAPY 31 巻 ( 4 ) 頁： 102628 2025年4月

Self-Organized Prediction-Classification-Superposition of Longitudinal Cognitive Decline in Alzheimer's Disease: An Application to Novel Clinical Research Methodology 査読有り

Sato H., Hanazawa R., Suzuki K., Hashizume A., Hirakawa A.

IEEE Journal of Biomedical and Health Informatics 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IEEE Journal of Biomedical and Health Informatics

Progressive cognitive decline spanning across decades is characteristic of Alzheimer's disease (AD). Various predictive models have been designed to realize its early onset and study the long-term trajectories of cognitive test scores across populations of interest. Research efforts have been geared towards superimposing patients' cognitive test scores with the long-term trajectory denoting gradual cognitive decline, while considering the heterogeneity of AD. Multiple trajectories representing cognitive assessment for the long-term have been developed based on various parameters, highlighting the importance of classifying several groups based on disease progression patterns. In this study, a novel method capable of self-organized prediction, classification, and the overlay of long-term cognitive trajectories based on short-term individual data was developed, based on statistical and differential equation modeling. Here, "self-organized"denotes a data-driven mechanism by which the prediction model adaptively configures its structure and parameters to classify individuals and estimate long-term trajectories. We validated the predictive accuracy of the proposed method on two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Japanese ADNI. We also presented two practical illustrations of the simultaneous evaluation of risk factor associated with both the onset and the longitudinal progression of AD, and an innovative randomized controlled trial design for AD that standardizes the heterogeneity of patients enrolled in a clinical trial. These resources would improve the power of statistical hypothesis testing and help evaluate the therapeutic effect. The application of predicting the trajectory of longitudinal disease progression goes beyond AD, and is especially relevant for progressive and neurodegenerative disorders.

DOI： 10.1109/JBHI.2025.3546020

Scopus

医薬品等の開発に関わる国内規制にはどのようなものがあるか査読有り

橋詰淳

神経治療学 42 巻 ( 1 ) 頁： 13 - 18 2025年

治療法開発に対する神経治療学会の取り組み：これまでとこれから査読有り

勝野雅央, 橋詰淳, 藤本陽子

神経治療学 42 巻 ( 1 ) 頁： 33 - 37 2025年

Comparison of Early-onset Efficacy of Anti-calcitonin Gene-related Peptide Monoclonal Antibodies for Patients with Migraine in Real-world Clinical Practice: Study Protocol for an Exploratory Clinical Trial Open Access

Tanei, T; Maesawa, S; Nishimura, Y; Ishizaki, T; Nagashima, Y; Hashida, M; Yamamoto, S; Ando, M; Kuwatsuka, Y; Hashizume, A; Wakabayashi, T; Saito, R

NEUROLOGIA MEDICO-CHIRURGICA 65 巻 ( 2 ) 頁： 71 - 80 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本脳神経外科学会

Three anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are available in Japan: galcanezumab, fremanezumab, and erenumab. Early-onset efficacy has been demonstrated for each CGRP-mAb in comparison with placebo, but differences among the drugs are unclear. Only galcanezumab requires 2 doses at the initial injection. This study is a multicenter, open-label, randomized, twogroup comparison trial, consisting of the random selection of a CGRP-mAb and 6 consecutive injections, and then discontinuation of the CGRP-mAb after 6 injections. The primary outcome is a comparison of early-onset efficacy between galcanezumab and both fremanezumab and erenumab after the initial injection. The secondary outcomes are comparisons between galcanezumab and both fremanezumab and erenumab, and between fremanezumab and erenumab as follows: weekly number of headache days, migraine days, and acute medication use are compared to baseline during one month after initial injection; time of subjectively perceiving onset of effect after initial injection; monthly changes in headache status from baseline to after third (3rd) injections; effective rates after initial and 3rd injections; improvement rates of depression scores between baseline and after 3rd injections; changes in number of absenteeism and presenteeism days in each month from baseline to after 3rd injections; proportion of ineffective cases after 3rd injections; recurrence rates and time to recurrence after CGRP-mAb discontinuation; effective rates of CGRP-mAb re-injections; detection of clinical factors associated with effectiveness after the initial and 3rd injections. The aim of this study is to investigate differences in early-onset efficacy among the CGRP-mAbs, and when and to what extent headache symptoms recur after discontinuation.

DOI： 10.2176/jns-nmc.2024-0201

Conventional magnetic resonance imaging key features for distinguishing pathologically confirmed corticobasal degeneration from its mimics: a retrospective analysis of the J-VAC study 査読有り Open Access

Sakurai, K; Tokumaru, AM; Yoshida, M; Saito, Y; Wakabayashi, K; Komori, T; Hasegawa, M; Ikeuchi, T; Hayashi, Y; Shimohata, T; Murayama, S; Iwasaki, Y; Uchihara, T; Sakai, M; Yabe, I; Tanikawa, S; Takigawa, H; Adachi, T; Hanajima, R; Fujimura, H; Hayashi, K; Sugaya, K; Hasegawa, K; Sano, T; Takao, M; Yokota, O; Miki, T; Kobayashi, M; Arai, N; Ohkubo, T; Yokota, T; Mori, K; Ito, M; Ishida, C; Idezuka, J; Toyoshima, Y; Kanazawa, M; Aoki, M; Hasegawa, T; Watanabe, H; Hashizume, A; Niwa, H; Yasui, K; Ito, K; Washimi, Y; Kubota, A; Toda, T; Nakashima, K; Aiba, I

NEURORADIOLOGY 66 巻 ( 11 ) 頁： 1917 - 1929 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neuroradiology

Purpose: Due to the indistinguishable clinical features of corticobasal syndrome (CBS), the antemortem differentiation between corticobasal degeneration (CBD) and its mimics remains challenging. However, the utility of conventional magnetic resonance imaging (MRI) for the diagnosis of CBD has not been sufficiently evaluated. This study aimed to investigate the diagnostic performance of conventional MRI findings in differentiating pathologically confirmed CBD from its mimics. Methods: Semiquantitative visual rating scales were employed to assess the degree and distribution of atrophy and asymmetry on conventional T1-weighted and T2-weighted images. Additionally, subcortical white matter hyperintensity (SWMH) on fluid-attenuated inversion recovery images were visually evaluated. Results: In addition to 19 patients with CBD, 16 with CBD mimics (progressive supranuclear palsy (PSP): 9, Alzheimer’s disease (AD): 4, dementia with Lewy bodies (DLB): 1, frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kDa(FTLD-TDP): 1, and globular glial tauopathy (GGT): 1) were investigated. Compared with the CBD group, the PSP-CBS subgroup showed severe midbrain atrophy without SWMH. The non-PSP-CBS subgroup, comprising patients with AD, DLB, FTLD-TDP, and GGT, showed severe temporal atrophy with widespread asymmetry, especially in the temporal lobes. In addition to over half of the patients with CBD, two with FTLD-TDP and GGT showed SWMH, respectively. Conclusion: This study elucidates the distinct structural changes between the CBD and its mimics based on visual rating scales. The evaluation of atrophic distribution and SWMH may serve as imaging biomarkers of conventional MRI for detecting background pathologies.

DOI： 10.1007/s00234-024-03432-w

Phase II/III and efficacy confirmation study of aceneuramic acid for GNE myopathy in Japan 査読有り

Suzuki, N; Yoshimura, MM; Katsuno, M; Takahashi, M; Yamashita, S; Oya, Y; Hashizume, A; Yamada, S; Nakamori, M; Izumi, R; Kato, M; Warita, H; Tateyama, M; Kuroda, H; Asada, R; Yamaguchi, T; Nishino, I; Aoki, M

NEUROMUSCULAR DISORDERS 43 巻 2024年10月

脊髄小脳変性症患者に対するHAL腰タイプを用いた在宅運動療法査読有り

岸本祥之, 橋詰淳, 山田晋一郎, 伊藤大輔, 小森祥太, 川瀬崇広, 近藤彩乃, 小原一輝, 森悠, 山本宗隆, 阿部友和, 戸田莉恵, 安永好宏, 勝野雅央

神経治療学 41 巻 ( 6 ) 頁： S299 - S299 2024年10月

球脊髄性筋萎縮症における骨脆弱性への治療法の検討査読有り

川瀬崇広, 橋詰淳, 山田晋一郎, 伊藤大輔, 岸本祥之, 小森祥太, 近藤彩乃, 森悠, 小原一輝, 山本宗隆

神経治療学 41 巻 ( 6 ) 頁： S280 - S280 2024年10月

AUTOANTIBODIES AGAINST DIHYDROLIPOAMIDE S-ACETYLTRANSFERASE IN IMMUNE-MEDIATED NEUROPATHIES 査読有り

Fukami, Y; Iijima, M; Koike, H; Yagi, S; Furukawa, S; Mouri, N; Ouchida, J; Murakami, A; Iida, M; Yokoi, S; Hashizume, A; Iguchi, Y; Imagama, S; Katsuno, M

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM 29 巻頁： S184 - S184 2024年8月

Comparing preprocessing strategies for 3D-Gene microarray data of extracellular vesicle-derived miRNAs 査読有り国際誌 Open Access

Takemoto, Y; Ito, D; Komori, S; Kishimoto, Y; Yamada, S; Hashizume, A; Katsuno, M; Nakatochi, M

BMC BIOINFORMATICS 25 巻 ( 1 ) 頁： 221 - 221 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Bioinformatics

Background: Extracellular vesicle-derived (EV)-miRNAs have potential to serve as biomarkers for the diagnosis of various diseases. miRNA microarrays are widely used to quantify circulating EV-miRNA levels, and the preprocessing of miRNA microarray data is critical for analytical accuracy and reliability. Thus, although microarray data have been used in various studies, the effects of preprocessing have not been studied for Toray’s 3D-Gene chip, a widely used measurement method. We aimed to evaluate batch effect, missing value imputation accuracy, and the influence of preprocessing on measured values in 18 different preprocessing pipelines for EV-miRNA microarray data from two cohorts with amyotrophic lateral sclerosis using 3D-Gene technology. Results: Eighteen different pipelines with different types and orders of missing value completion and normalization were used to preprocess the 3D-Gene microarray EV-miRNA data. Notable results were suppressed in the batch effects in all pipelines using the batch effect correction method ComBat. Furthermore, pipelines utilizing missForest for missing value imputation showed high agreement with measured values. In contrast, imputation using constant values for missing data exhibited low agreement. Conclusions: This study highlights the importance of selecting the appropriate preprocessing strategy for EV-miRNA microarray data when using 3D-Gene technology. These findings emphasize the importance of validating preprocessing approaches, particularly in the context of batch effect correction and missing value imputation, for reliably analyzing data in biomarker discovery and disease research.

DOI： 10.1186/s12859-024-05840-4

Safety and efficacy of aceneuramic acid in GNE myopathy: open-label extension study 査読有り国際誌 Open Access

Suzuki, N; Mori-Yoshimura, M; Katsuno, M; Takahashi, MP; Yamashita, S; Oya, Y; Hashizume, A; Yamada, S; Nakamori, M; Izumi, R; Kato, M; Warita, H; Tateyama, M; Kuroda, H; Asada, R; Yamaguchi, T; Nishino, I; Aoki, M

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 95 巻 ( 11 ) 頁： 1093 - 1094 2024年6月

Autoantibodies Against Dihydrolipoamide S-Acetyltransferase in Immune-Mediated Neuropathies 査読有り国際誌 Open Access

Fukami, Y; Iijima, M; Koike, H; Yagi, S; Furukawa, S; Mouri, N; Ouchida, J; Murakami, A; Iida, M; Yokoi, S; Hashizume, A; Iguchi, Y; Imagama, S; Katsuno, M

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION 11 巻 ( 2 ) 頁： e200199 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neurology: Neuroimmunology and NeuroInflammation

Background and Objectives This study aimed to identify disease-related autoantibodies in the serum of patients with immune-mediated neuropathies including chronic inflammatory demyelinating polyneuropathy (CIDP) and to investigate the clinical characteristics of patients with these antibodies. Methods Proteins extracted from mouse brain tissue were used to react with sera from patients with CIDP by western blotting (WB) to determine the presence of common bands. Positive bands were then identified by mass spectrometry and confirmed for reactivity with patient sera using enzyme-linked immunosorbent assay (ELISA) and WB. Reactivity was further confirmed by cell-based and tissue-based indirect immunofluorescence assays. The clinical characteristics of patients with candidate autoantibody-positive CIDP were analyzed, and their association with other neurologic diseases was also investigated. Results Screening of 78 CIDP patient sera by WB revealed a positive band around 60–70 kDa identified as dihydrolipoamide S-acetyltransferase (DLAT) by immunoprecipitation and mass spectrometry. Serum immunoglobulin G (IgG) and IgM antibodies’ reactivity to recombinant DLAT was confirmed using ELISA and WB. A relatively high reactivity was observed in 29 of 160 (18%) patients with CIDP, followed by patients with sensory neuropathy (6/58, 10%) and patients with MS (2/47, 4%), but not in patients with Guillain-Barré syndrome (0/27), patients with hereditary neuropathy (0/40), and healthy controls (0/26). Both the cell-based and tissue-based assays confirmed reactivity in 26 of 33 patients with CIDP. Comparing the clinical characteristics of patients with CIDP with anti-DLAT antibodies (n = 29) with those of negative cases (n = 131), a higher percentage of patients had comorbid sensory ataxia (69% vs 37%), cranial nerve disorders (24% vs 9%), and malignancy (20% vs 5%). A high DLAT expression was observed in human autopsy dorsal root ganglia, confirming the reactivity of patient serum with mouse dorsal root ganglion cells. Discussion Reactivity to DLAT was confirmed in patient sera, mainly in patients with CIDP. DLAT is highly expressed in the dorsal root ganglion cells, and anti-DLAT antibody may serve as a biomarker for sensory-dominant neuropathies.

DOI： 10.1212/NXI.0000000000200199

PMDAでの経験とその後　―アカデミアでの倫理指針下研究支援― 査読有り

橋詰淳

神経治療学 41 巻 ( 3 ) 頁： 411 - 414 2024年

球脊髄性筋萎縮症に対するリュープロレリン酢酸塩の薬事承認とその後査読有り

橋詰淳

神経治療学 41 巻 ( 6 ) 頁： S225 - S225 2024年

Impact of periodic neck ultrasonography on locoregional disease control in surveillance after total thyroidectomy for patients with low- and intermediate-risk papillary thyroid carcinoma: a propensity score-matched study Open Access

Inaishi, T; Takeuchi, D; Ichikawa, T; Inaguma, G; Hashizume, A; Okazaki, M; Masuda, N; Kikumori, T

ENDOCRINE JOURNAL 71 巻 ( 12 ) 頁： 1135 - 1143 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本内分泌学会

This study aimed to evaluate the impact of periodic neck ultrasonography (US) on postoperative surveillance for locoregional disease control of patients with low-and intermediate-risk papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. This retrospective cohort study included patients with PTC who underwent total thyroidectomy and central neck dissection at our institution between January, 2000 and December, 2016. The patients were divided into two groups: the physical examination (PE) group (follow-up by PE without periodic US) and the US group (follow-up by PE with periodic US). Serum thyroglobulin levels were measured periodically in both groups. Propensity score matching was used to rigorously balance the significant variables and assess the 10-year postoperative outcomes between the groups. Of the 189 patients, 150 were included after matching (75 in each group). There were no significant differences between the two groups in terms of background characteristics. The median follow-up period was 127.9 months. There was no significant difference in locoregional relapse-free survival between the PE and US groups (97.0 vs. 98.7%, p = 0.541). The overall survival was 96.7% and 98.7% in the PE and US groups, respectively, with no significant difference (p = 0.364). This study demonstrated that the addition of periodic US to PE for postoperative surveillance of patients with low-and intermediate-risk PTC who underwent total thyroidectomy did not significantly affect locoregional control.

DOI： 10.1507/endocrj.ej24-0194

Efficacy of the latest new stimulation patterns of spinal cord stimulation for intractable neuropathic pain compared to conventional stimulation: study protocol for a clinical trial 査読有り国際誌 Open Access

Tanei, T; Maesawa, S; Nishimura, Y; Nagashima, Y; Ishizaki, T; Ando, M; Kuwatsuka, Y; Hashizume, A; Kurasawa, S; Saito, R

TRIALS 24 巻 ( 1 ) 頁： 604 - 604 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Trials

Background: Spinal cord stimulation (SCS) is one of the neuromodulation therapies for chronic neuropathic pain. The conventional paresthesia-based SCS involves the application of tonic stimulation that induces a sense of paresthesia. Recently, new SCS stimulation patterns without paresthesia have been developed. Differential target multiplexed (DTM) stimulation and fast-acting subperception therapy (FAST) stimulation are the latest paresthesia-free SCS patterns. Methods: A single-center, open-label, crossover, randomized clinical trial to investigate the superiority of SCS using the latest new stimulation patterns over conventional tonic stimulation for neuropathic pain is planned. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). In the SCS trial, participants will be randomly assigned to 4 groups receiving stimulation, including tonic, DTM, and FAST. Each stimulation will then be performed for 2 days, and a visual analog scale (VAS) for pain will be evaluated before and after each stimulation pattern. A stimulation-off period for 1 day is set between each stimulation pattern to wash out the residual previous stimulation effects. Pain improvement is defined as more than 33% reduction in the pain VAS. The primary analysis will compare pain improvement between the new stimulation patterns and the conventional tonic stimulation pattern in the SCS trial. The secondary outcomes will be evaluated as follows: (1) the relationships between causative disease and improvement rate by each stimulation pattern; (2) comparison of pain improvement between the DTM and FAST stimulation patterns in all cases and by causative disease; (3) changes in assessment items preoperatively to 24 months after the implantation; (4) preoperative factors associated with long-term effects defined as continuing for more than 12 months; and (5) adverse events related to this study 3 months after the implantation. Discussion: This study aims to clarify the effectiveness of the latest new stimulation patterns compared to the conventional tonic stimulation. In addition, which stimulation pattern is most effective for which kind of causative disease will be clarified. Trial registration: Japan Registry of Clinical Trials (jRCT) 1,042,220,094. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is an approved member of the Primary Registry Network of WHO ICTRP.

DOI： 10.1186/s13063-023-07637-x

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