論文 - 手塚　俊樹

Clinical characteristics and pathophysiological properties of newly discovered LRRK2 variants associated with Parkinson's disease

Tezuka, T., Ishiguro, M., Taniguchi, D., Osogaguchi, E., Shiba-Fukushima, K., Ogata, J., Ishii, R., Ikeda, A., Li, Y., Yoshino, H., Matsui, T., Kaida, K., Funayama, M., Nishioka, K., Kumazawa, F., Matsubara, T., Tsuda, H., Saito, Y., Murayama, S., Imai, Y. and Hattori, N.

Neurobiol Dis 199   106571 2024年09月

ISSN  0969-9961

　概要を見る

Leucine-rich repeat kinase 2 (LRRK2) is the most common gene responsible for familial Parkinson's disease (PD). The gene product of LRRK2 contains multiple protein domains, including armadillo repeat, ankyrin repeat, leucine-rich repeat (LRR), Ras-of-complex (ROC), C-terminal of ROC (COR), kinase, and WD40 domains. In this study, we performed genetic screening of LRRK2 in our PD cohort, detecting sixteen LRRK2 rare variants. Among them, we selected seven variants that are likely to be familial and characterized them in terms of LRRK2 protein function, along with clinical information and one pathological analysis. The seven variants were S1120P and N1221K in the LRR domain; I1339M, S1403R, and V1447M in the ROC domain; and I1658F and D1873H in the COR domain. The kinase activity of the LRRK2 variants N1221K, S1403R, V1447M, and I1658F toward Rab10, a well-known phosphorylation substrate, was higher than that of wild-type LRRK2. LRRK2 D1873H showed enhanced self-association activity, whereas LRRK2 S1403R and D1873H showed reduced microtubule-binding activity. Pathological analysis of a patient with the LRRK2 V1447M variant was also performed, which revealed Lewy pathology in the brainstem. No functional alterations in terms of kinase activity, self-association activity, and microtubule-binding activity were detected in LRRK2 S1120P and I1339M variants. However, the patient with PD carrying LRRK2 S1120P variant also had a heterozygous Glucosylceramidase beta 1 (GBA1) L444P variant. In conclusion, we characterized seven LRRK2 variants potentially associated with PD. Five of the seven variants in different LRRK2 domains exhibited altered properties in kinase activity, self-association, and microtubule-binding activity, suggesting that each domain variant may contribute to disease progression in different ways.

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Repeated Intravenous Methylprednisolone May Prevent Deterioration of Hypertrophic Pachymeningitis in Rosai-Dorfman Disease

Tezuka, T., Nukariya, T., Takahashi, N., Kufukihara, K., Tsuyama, N., Terui, Y., Kameyama, K., Nakahara, J. and Takizawa, T.

Intern Med 2024年07月

ISSN  0918-2918

　概要を見る

Rosai-Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytosis. Although 20% of patients with RDD have spontaneous remission, some cases with central nervous system (CNS) involvement require surgery or systemic treatment. We encountered a case of RDD in which hypertrophic pachymeningitis was diffuse, eliminating the need for surgical intervention. A 72-year-old Japanese man was diagnosed with RDD based on pathological lymph node findings. Repeated intravenous methylprednisolone (IVMP) administration resolved and stabilized the hypertrophic pachymeningitis without any sequelae. If surgery or anticancer medications are contraindicated, repeated IVMP may be a good therapeutic option for CNS-associated RDD.

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Cerebral Venous Thrombosis Mimicking Limbic Encephalitis

Tezuka, T., Takahashi, N., Tokuyasu, D., Azami, S., Sekiguchi, K., Takizawa, T., Izawa, Y., Nakahara, J. and Katsumata, M.

Intern Med 63 （ 9 ） 1277 - 1280 2024年05月

ISSN  0918-2918

　概要を見る

Cerebral venous thrombosis (CVT) is challenging to diagnose, as it presents with variable symptoms. We encountered a complicated case of CVT that mimicked limbic encephalitis due to sensory aphasia. Based on the characteristic magnetic resonance imaging findings, this 72-year-old Japanese man was later confirmed to have CVT, the cause of which was periodontitis due to Eikenella corrodens, a Gram-negative facultative anaerobic that is part of the mouth's normal flora. The symptoms improved without sequelae following anticoagulation treatment and antibiotics. Clinicians should consider CVT as a differential diagnosis when unexplainable neurological symptoms suggesting limbic encephalitis are observed.

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Amyloid-β prediction machine learning model using source-based morphometry across neurocognitive disorders

Momota, Y., Bun, S., Hirano, J., Kamiya, K., Ueda, R., Iwabuchi, Y., Takahata, K., Yamamoto, Y., Tezuka, T., Kubota, M., Seki, M., Shikimoto, R., Mimura, Y., Kishimoto, T., Tabuchi, H., Jinzaki, M., Ito, D. and Mimura, M.

Sci Rep 14 （ 1 ） 7633 2024年04月

ISSN  2045-2322

　概要を見る

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer's disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aβ) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aβ-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aβ-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

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【10年間で登場した薬剤の市販後を総点検!病棟頻用薬の通信簿】(PART.2)承認後3年〜7年未満(2018〜2021)　新規MAO-B阻害薬　サフィナミド,ラサギリン

手塚, 俊樹 and 関, 守信

薬事 66 （ 6 ） 1135 - 1141 2024年04月

ISSN  0016-5980

Validation study of the Japanese version of the King's Parkinson's Disease Pain Scale and the King's Parkinson's Disease Pain Questionnaire

Kurihara, K., Fujioka, S., Mizutani, Y., Watanabe, H., Iwaoka, K., Maeda, T., Seki, M., Tezuka, T., Nakahara, J., Konno, T., Ishiguro, T., Onodera, O., Asano, Y., Takahashi, K., Rizos, A., Chaudhuri, K. R. and Tsuboi, Y.

Parkinsonism Relat Disord 120   106012 2024年03月

ISSN  1353-8020

　概要を見る

INTRODUCTION: The King's Parkinson's Disease Pain Scale (KPPS)/King's Parkinson's Disease Pain Questionnaire (KPPQ) was developed as a tool to quantitatively assess pain in patients with Parkinson's disease (PwPD). Here, we conducted a Japanese multicenter validation study to verify the reliability of KPPS/KPPQ in Japanese PwPD. METHODS: PwPD, ≥20 years, with unexplained pain were included; those with a definitive primary cause of pain other than PD were excluded. A total of 151 patients who fulfilled the criteria were analyzed, and test-retest reliability was investigated in 25 individuals. RESULTS: The 151 patients included 101 women (66.9 %); mean age 68.3 ± 9.9 years, mean disease duration 9.2 ± 5.2 years. The most frequent pain type in the KPPS classification was musculoskeletal pain (82.8 %). There was a positive correlation between KPPS total score and the Non-Motor Symptoms Scale (NMSS) total score, NMSS item 27, the Parkinson's disease sleep scale-version 2 (PDSS-2) total score, PDSS-2 item 10, the Parkinson's Disease Questionnaire-8 (PDQ-8) summary index and PDQ-8 item 7. Cronbach's alpha of KPPS was 0.626 (0.562-0.658) and the intraclass correlation coefficient of test-retest reliability was 0.740. Cronbach's alpha of KPPQ was 0.660 (0.617-0.705) and a test-retest reliability of kappa coefficient was 0.593 (0.0-1.0). CONCLUSIONS: KPPS correlated well with other scales for assessing pain. KPPS correlated well with patients' quality of life, non-motor symptoms, and sleep disturbances. The reproducibility of KPPS/KPPQ makes it suitable for continuous evaluation of the same patient. On the other hand, the internal consistency of KPPS/KPPQ is rather low.

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パーキンソン病に対する脳深部刺激療法後に4-condition testが病態の把握に有用であった1例

大草, 翔平, 大河内, 遼太郎, 坂井, 悠人, 忽滑谷, 智紀, 小杉, 健三, 工藤, 駿, 手塚, 俊樹, 二瓶, 義廣, 秋山, 武紀, 内田, 裕之, 三村, 將, 戸田, 正博, 小林, 正人, 中原, 仁 and 関, 守信

日本定位・機能神経外科学会プログラム・抄録集 63回   121 2024年01月

Systemic lupus erythematosus mimicking retinal migraine: a case report

Tezuka, T., Shibata, M., Hanaoka, H., Izawa, Y., Kikuchi, T., Akino, K., Ozawa, Y., Saito, M., Kaneko, Y., Nakahara, J. and Takizawa, T.

Cephalalgia 43 （ 12 ） 3331024231219477 2023年12月

ISSN  0333-1024

　概要を見る

BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

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【腫瘍随伴症候群】免疫学的機序によるもの　抗NMDA受容体抗体脳炎

手塚, 俊樹 and 鈴木, 重明

臨床検査 67 （ 11 ） 1278 - 1283 2023年11月

ISSN  0485-1420

　概要を見る

＜文献概要＞POINT　●抗N-メチル-D-アスパラギン酸(NMDA)受容体抗体脳炎は,最も頻度が高い自己免疫性脳炎であり,急性・亜急性に発症する精神症状を特徴とし,抗NMDA受容体抗体によるNMDA受容体の内在化と機能低下が主な病態である.●抗NMDA受容体抗体の測定法としては,CBA法と免疫組織化学染色(IHC)を用いたTBA法があり,いずれの方法も血清・髄液における抗NMDA受容体抗体の検出が可能であるが,髄液のほうが感度・特異度ともに優れている.●わが国における抗NMDA抗体の測定法に関しては,商業ベースのCBA法があるが,保険適用外の検査であり,結果が出るまでに週単位の時間がかかる.より精度の高いTBA法に関しては,さらに施行可能な施設が限られる.●抗NMDA受容体抗体が治療により減少することで,内在化したNMDA受容体が再度シナプス膜上に戻り回復するため,早期の診断と免疫治療が患者の生命,機能予後の改善に重要である.

脊髄血管造影が鑑別の一助となった脊髄High-grade gliomaの一例

吉田, 昌平, 徳安, 大輝, 高橋, 洵行, 関口, 耕史, 手塚, 俊樹, 勝又, 雅裕, 伊澤, 良兼 and 中原, 仁

臨床神経学 63 （ 11 ） 768 2023年11月

ISSN  0009-918X

Source-based morphometryを用いた機械学習モデルでの神経認知障害のアミロイドβ予測

百田, 友紀, 文, 鐘玉, 平野, 仁一, 神谷, 慶, 上田, 亮, 岩渕, 雄, 高畑, 圭輔, 山本, 保天, 手塚, 俊樹, 窪田, 真人, 関, 守信, 色本, 涼, 三村, 悠, 岸本, 泰士郎, 田渕, 肇, 陣崎, 雅弘, 伊東, 大介 and 三村, 將

Dementia Japan 37 （ 4 ） 657 2023年10月

ISSN  1342-646X

Performance of plasma Aβ42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status

Bun, S., Ito, D., Tezuka, T., Kubota, M., Ueda, R., Takahata, K., Moriguchi, S., Kurose, S., Momota, Y., Suzuki, N., Morimoto, A., Hoshino, Y., Seki, M., Mimura, Y., Shikimoto, R., Yamamoto, Y., Hoshino, T., Sato, Y., Tabuchi, H. and Mimura, M.

Alzheimers Res Ther 15 （ 1 ） 149 2023年09月

　概要を見る

BACKGROUND: Plasma biomarkers have emerged as promising screening tools for Alzheimer's disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection. METHODS: We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson's disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). RESULTS: Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed (18)F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman's rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive. CONCLUSION: Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.

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"Missing-piece" sign with dural arteriovenous fistula at craniocervical junction: A case report

Tezuka, T., Nukariya, T., Katsumata, M., Miyauchi, T., Tokuyasu, D., Azami, S., Izawa, Y., Nagoshi, N., Fujiwara, H., Mizutani, K., Akiyama, T., Toda, M., Nakahara, J. and Nishimoto, Y.

J Stroke Cerebrovasc Dis 32 （ 7 ） 107152 2023年07月

ISSN  1052-3057

　概要を見る

OBJECTIVES: Spinal dural arteriovenous fistula (sDAVF) is a rare and often underdiagnosed spinal disease. Early diagnosis is required because the deficits are reversible and delays in treatment cause permanent morbidity. Although the abnormal vascular flow void is a critical radiographic feature of sDAVF, they are not always present. A characteristic enhancement pattern of sDAVF has been recently reported as the "missing-piece" sign which can lead to the early and correct diagnosis. METHODS: We presented imaging findings, treatment decisions, and the outcome of a rare case of sDAVF, in which the "missing-piece" sign appeared atypical. RESULTS: A 60-year-old woman developed numbness and weakness in her extremities. Spinal MRI revealed longitudinal hyperintensity in the T2-weighted image, extending from the thoracic level to medulla oblongata. At first, myelopathy with inflammation or tumor was suspected because of the lack of flow voids and vascular abnormalities in CT-angiography and MR-DSA. However, we administered intravenous methylprednisolone and her symptom got worse with the appearance of the "missing-piece" sign. Then, we successfully diagnosed sDAVF by angiography. The "missing-piece" sign was considered to derive from inconsistency of the intrinsic venous system of spinal cord, with the abrupt segments without enhancement. The same etiology was considered in our case. CONCLUSIONS: Detecting the "missing-piece" sign can lead to the correct diagnosis of sDAVF, even if the sign appeared atypical.

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Dysautonomia associated with immune checkpoint inhibitors

Tezuka, T., Okuzumi, S., Nakashima, C., Ide, T., Imai, S., Mitsuboshi, S., Kuwahara, Y., Takizawa, T., Seki, M., Minematsu, N., Aragane, N., Nakahara, J., Hori, S., Nakane, S. and Suzuki, S.

J Neurol 270 （ 7 ） 3413 - 3423 2023年07月

ISSN  0340-5354

　概要を見る

OBJECTIVE: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). METHODS: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. RESULTS: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. CONCLUSION: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

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パーキンソン病患者に対するオンラインリハビリの日常生活動作と生活の質への影響

大草, 翔平, 三枝, 洋喜, 宮川, 和也, 堤, 裕太, 石田, 沙瑛, 西潟, 京子, 忽滑谷, 智紀, 手塚, 俊樹, 二瓶, 義廣, 北川, 泰啓, 久保, 紳一郎, 鈴木, 則宏, 中原, 仁 and 関, 守信

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 17回   102 2023年07月

Anti-N-methyl-D-aspartate receptor encephalitis with concurrent human herpes virus-6A deoxyribonucleic acid detection: An autopsy case

Shimohama, S., Iizuka, T., Takizawa, T., Watanabe, N., Tezuka, T., Matsuda, K., Yamanoi, K., Kanazawa, N., Kawamura, Y., Yoshikawa, T., Suzuki, T., Takao, M., Nakahara, J. and Izawa, Y.

Neuropathology 43 （ 3 ） 257 - 261 2023年06月

ISSN  0919-6544

　概要を見る

We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3-4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

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ニボルマブ投与後に心筋炎を合併したirAE筋炎の1例

忽滑谷, 智紀, 徳安, 大輝, 手塚, 俊樹, 西本, 祥仁, 水野, 里香, 浜本, 康夫, 鈴木, 重明 and 中原, 仁

日本内科学会関東地方会 685回   41 2023年03月

免疫チェックポイント阻害剤関連の自律神経障害

手塚, 俊樹, 奥隅, 真一, 中島, 千穂, 今井, 俊吾, 峰松, 直人, 荒金, 尚子, 滝沢, 翼, 関, 守信, 中原, 仁 and 鈴木, 重明

日本内科学会雑誌 112 （ 臨増 ） 188 2023年02月

ISSN  0021-5384

Impact of Amyloid and Tau PET on Changes in Diagnosis and Patient Management

Shimohama, S., Tezuka, T., Takahata, K., Bun, S., Tabuchi, H., Seki, M., Momota, Y., Suzuki, N., Morimoto, A., Iwabuchi, Y., Kubota, M., Yamamoto, Y., Sano, Y., Shikimoto, R., Funaki, K., Mimura, Y., Nishimoto, Y., Ueda, R., Jinzaki, M., Nakahara, J., Mimura, M. and Ito, D.

Neurology 100 （ 3 ） e264 - e274 2023年01月

ISSN  0028-3878

　概要を見る

BACKGROUND AND OBJECTIVES: Previous studies have evaluated the diagnostic effect of amyloid PET in selected research cohorts. However, these studies did not assess the clinical impact of the combination of amyloid and tau PETs. Our objective was to evaluate the association of the combination of 2 PETs with changes in diagnosis, treatment, and management in a memory clinic cohort. METHODS: All participants underwent amyloid [(18)F]florbetaben PET and tau PET using [(18)F]PI-2620 or [(18)F]Florzolotau, which are potentially useful for the diagnosis of non-Alzheimer disease (AD) tauopathies. Dementia specialists determined a pre- and post-PET diagnosis that existed in both a clinical syndrome (cognitive normal [CN], mild cognitive impairment [MCI], and dementia) and suspected etiology, with a confidence level. In addition, the dementia specialists determined patient treatment in terms of ancillary investigations and management. RESULTS: Among 126 registered participants, 84.9% completed the study procedures and were included in the analysis (CN [n = 40], MCI [n = 25], AD [n = 20], and non-AD dementia [n = 22]). The etiologic diagnosis changed in 25.0% in the CN, 68.0% in the MCI, and 23.8% with dementia. Overall changes in management between pre- and post-PET occurred in 5.0% of CN, 52.0% of MCI, and 38.1% of dementia. Logistic regression analysis revealed that tau PET has stronger associations with change management than amyloid PET in all participants and dementia groups. DISCUSSION: The combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia, and the second-generation tau PET has a strong impact on the changes in diagnosis and management in memory clinics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the combination of amyloid and tau PETs was associated with changes in management and diagnosis of MCI and dementia.

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Findings of (18) F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample

Bun, S., Moriguchi, S., Tezuka, T., Sato, Y., Takahata, K., Seki, M., Nakajima, S., Yamamoto, Y., Sano, Y., Suzuki, N., Morimoto, A., Ueda, R., Tabuchi, H., Ito, D. and Mimura, M.

Neuropsychopharmacol Rep 42 （ 4 ） 437 - 448 2022年12月

ISSN  2574-173x

　概要を見る

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions. AIMS: (18) F-PI-2620 is one of the second-generation tau PET tracers with presumably less off-target binding than its predecessors. Although a few clinical studies have recently reported the use of (18) F-PI-2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined. METHODS: In the present pilot study, we performed (18) F-PI-2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p-tau181 as well as cognitive test scores were also analyzed. RESULTS: The uptake of (18) F-PI-2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p-tau181 levels, as well as with MMSE and ADAS-cog scores. DISCUSSION & CONCLUSION: Our results add to accumulating evidence suggesting that (18) F-PI-2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.

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再発性非小細胞肺癌が疑われ、ニボルマブ、イピリムマブを投与したのち脳炎と自律神経障害を発症した61歳男性例

手塚, 俊樹, 奥隅, 真一, 峰松, 直人, 滝沢, 翼, 関, 守信, 中原, 仁 and 鈴木, 重明

臨床神経学 62 （ 12 ） 972 2022年12月

ISSN  0009-918X

Impact of Amyloid and Tau PET Combination on Changes in Diagnosis and Management

下濱, 祥, 手塚, 俊樹, 高畑, 圭輔, 文, 鐘玉, 田渕, 肇, 関, 守信, 百田, 友紀, 三村, 悠, 西本, 祥仁, 色本, 涼, 船木, 桂, 窪田, 真人, 山本, 保天, 佐野, 康徳, 中原, 仁, 三村, 將 and 伊東, 大介

老年精神医学雑誌 33 （ 増刊II ） 336 2022年11月

ISSN  0915-6305

【脊椎・脊髄障害update】脊椎・脊髄障害症候群　Klippel-Feil症候群

手塚, 俊樹 and 滝沢, 翼

Clinical Neuroscience 40 （ 11 ） 1462 - 1464 2022年11月

ISSN  0289-0585

Impact of Amyloid and Tau PET Combination on Changes in Diagnosis and Management

下濱, 祥, 手塚, 俊樹, 高畑, 圭輔, 文, 鐘玉, 田渕, 肇, 関, 守信, 百田, 友紀, 三村, 悠, 西本, 祥仁, 色本, 涼, 船木, 桂, 窪田, 真人, 山本, 保天, 佐野, 康徳, 中原, 仁, 三村, 將 and 伊東, 大介

Dementia Japan 36 （ 4 ） 793 2022年10月

ISSN  1342-646X

Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson's disease

Tezuka, T., Taniguchi, D., Sano, M., Shimada, T., Oji, Y., Tsunemi, T., Ikeda, A., Li, Y., Yoshino, H., Ogata, J., Shiba-Fukushima, K., Funayama, M., Nishioka, K., Imai, Y. and Hattori, N.

NPJ Parkinsons Dis 8 （ 1 ） 97 2022年08月

ISSN  2373-8057

　概要を見る

Missense variants in leucine-rich repeat kinase 2 (LRRK2) lead to familial and sporadic Parkinson's disease (PD). The pathological features of PD patients with LRRK2 variants differ. Here, we report an autopsy case harboring the LRRK2 G2385R, a risk variant for PD occurring mainly in Asian populations. The patient exhibited levodopa-responsive parkinsonism at the early stage and visual hallucinations at the advanced stage. The pathological study revealed diffuse Lewy bodies with neurofibrillary tangles, amyloid plaques, and mild signs of neuroinflammation. Biochemically, detergent-insoluble phospho-α-synuclein was accumulated in the frontal, temporal, entorhinal cortexes, and putamen, consistent with the pathological observations. Elevated phosphorylation of Rab10, a substrate of LRRK2, was also prominent in various brain regions. In conclusion, G2385R appears to increase LRRK2 kinase activity in the human brain, inducing a deleterious brain environment that causes Lewy body pathology.

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Progressive Ataxia and Palatal Tremor Showing Characteristic Tau Depositions in [(18) F]PM-PBB3 PET

Tezuka, T., Takahata, K., Tagai, K., Ueda, R., Ito, D., Takeda, H., Takahashi, S., Nakahara, J., Higuchi, M. and Seki, M.

Mov Disord 37 （ 6 ） 1317 - 1319 2022年06月

ISSN  0885-3185

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(XIV章)神経(脳神経内科)系疾患における新たな診断技術・臨床検査の動向　神経(脳神経内科)系疾患における新たな診断技術・臨床検査の動向

手塚, 俊樹

脳神経内科学レビュー 2022-'23   426 - 433 2022年03月

ISSN  2436-7974

[The questionnaire survey regarding the impact of COVID-19 pandemic on Parkinson's disease patients]

Tezuka, T., Osada, T., Terayama, Y., Kubota, M., Okusa, S., Shiihashi, G., Kubo, S. I., Suzuki, N., Nakahara, J. and Seki, M.

Rinsho Shinkeigaku 62 （ 1 ） 8 - 14 2022年01月

ISSN  0009-918x

　概要を見る

We conducted the multicenter questionnaire survey targeting patients with Parkinson's disease (PD) in order to investigate the impacts on their daily lives and their requests to hospitals in the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mainly using open-ended questionnaire, we asked their anxiety, troubles they are facing, and requests toward hospitals in the pandemic of SARS-CoV-2. Two hundred fifth-eight PD patients answered the questionnaire. There were various opinions about anxiety such as "PD patients are susceptible and vulnerable to SARS-CoV-2" (36.8%). Concerning the troubles in the pandemic, the most frequent answer was that they couldn't participate in the rehabilitation and elderly day care (38.4%). Relatively many PD patients requested telemedicine (29.5%), whereas some people hoped face-to-face medical care (8.1%). There were demands about the delivery of medications (50.0%), the establishment of telephone consultations (43.8%), resources for rehabilitation at home (43.8%). The medical care adapted to the anxiety, trouble and requests of PD patients will be required in the era when we have to live with SARS-CoV-2.

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パーキンソン病患者を対象とした新型コロナウイルス感染拡大の影響に関するアンケート調査

手塚, 俊樹, 長田, 高志, 寺山, 靖夫, 窪田, 真人, 大草, 翔平, 椎橋, 元, 久保, 紳一郎, 鈴木, 則宏, 中原, 仁 and 関, 守信

臨床神経学 62 （ 1 ） 8 - 14 2022年01月

ISSN  0009-918X

　概要を見る

新型コロナウイルス流行によるパーキンソン病(Parkinson's disease,以下PDと略記)患者の生活への影響や医療現場への要望を調査すべく,PD患者を対象に多施設でアンケート調査を実施した.流行に伴う不安,問題,医療現場への要望を,主にオープン形式で質問し,258名から回答を得た.不安としてはPDがあると感染・重症化しやすいのではないかというものが多く,問題としてはリハビリ等に行けなくなったという回答が多かった.要望としては,電話診療を希望する意見が多かったが,対面診療を希望する声も一定数得られた.薬の宅配,電話相談窓口の設置,自宅でできるリハビリ資材を希望する意見が多かった.PD患者の不安・問題・要望に合わせた医療が求められる.(著者抄録)

Case report: Non-Alzheimer's disease tauopathy with logopenic variant primary progressive aphasia diagnosed using amyloid and tau PET

Momota, Y., Konishi, M., Takahata, K., Kishimoto, T., Tezuka, T., Bun, S., Tabuchi, H., Ito, D. and Mimura, M.

Front Neurol 13   1049113 2022年

ISSN  1664-2295

　概要を見る

We report a patient with logopenic variant primary progressive aphasia (lv-PPA) who was diagnosed as having non-Alzheimer's disease (AD) tauopathy after multiple biophysical/biological examinations, including amyloid and (18)F-florzolotau tau positron emission tomography (PET), had been performed. A woman in her late 60s who had previously been diagnosed as having AD was referred to us for a further, detailed examination. She had been unaware of any symptoms at the time of AD diagnosis, but she subsequently became gradually aware of a speech impairment. She talked nearly completely and fluently, although she occasionally exhibited word-finding difficulty and made phonological errors during naming, word fluency testing, and sentence repetition; these findings met the criteria for the diagnosis of lv-PPA, which is known to be observed more commonly in AD than in other proteinopathies. Magnetic resonance imaging, single photon emission computed tomography, and plasma phosphorylated tau and plasma neurofilament light chain measurements showed an AD-like pattern. However, both (11)C-Pittsburgh compound-B and (18)F-florbetaben amyloid PET showed negative results, whereas (18)F-florzolotau tau PET yielded positive results, with radio signals predominantly in the left superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and frontal operculum. Whole-genome sequencing revealed no known dominantly inherited mutations in AD or frontotemporal lobar degeneration genes, including the genes encoding amyloid precursor protein, microtubule-associated protein tau, presenilin 1 and 2. To the best of our knowledge, this patient was a rare case of lv-PPA who was diagnosed as having non-AD tauopathy based on the results of multiple examinations, including whole-genome sequencing, plasma measurement, and amyloid and (18)F-florzolotau tau PET. This case underscores the clinicopathologically heterogeneous nature of this syndrome.

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Evaluation of glymphatic system using diffusion MRI in AD spectrum

窪田, 真人, 手塚, 俊樹, 佐藤, 義明, 上田, 亮, 伊東, 大介 and 関, 守信

Dementia Japan 35 （ 4 ） 617 2021年10月

ISSN  1342-646X

[18F]PM-PBB3 and plasma p-tau181 and NfL for Alzheimer's disease

手塚, 俊樹, 高畑, 圭輔, 関, 守信, 文, 鐘玉, 佐藤, 義明, 上田, 亮, 窪田, 真人, 森口, 翔, 中島, 振一郎, 鈴木, 菜摘, 森本, 綾香, 百田, 友紀, 岩渕, 雄, 馬島, 恭子, 田渕, 肇, 陣崎, 雅弘, 三村, 將, 中原, 仁 and 伊東, 大介

Dementia Japan 35 （ 4 ） 611 2021年10月

ISSN  1342-646X

聴覚失認とプロソディ障害で発症し、[18F]PM-PBB3 PETで診断に至ったtauopathyの1例

馬島, 恭子, 小西, 海香, 手塚, 俊樹, 高畑, 圭輔, 岡本, 康秀, 関, 守信, 田淵, 肇, 伊東, 大介 and 三村, 將

Dementia Japan 35 （ 4 ） 623 2021年10月

ISSN  1342-646X

パーキンソン病患者を対象とした新型コロナウイルス感染拡大に関するアンケート(第1報)

手塚, 俊樹, 長田, 高志, 寺山, 靖夫, 窪田, 真人, 大草, 翔平, 鈴木, 則宏, 久保, 紳一郎, 椎橋, 元, 中原, 仁 and 関, 守信

臨床神経学 61 （ Suppl. ） S319 2021年09月

ISSN  0009-918X

語義失語様の症状を呈す進行性失語で非AD・tauopathyが疑われる一例

小西, 海香, 斎藤, 文恵, 手塚, 俊樹, 田渕, 肇 and 三村, 將

日本神経心理学会総会プログラム・予稿集 45回   114 2021年09月

A case of tauopathy with auditory agnosia and dysprosody diagnosed by [(18)F]PM-PBB3 tau PET scan

Mashima, K., Konishi, M., Tezuka, T., Ito, D. and Mimura, M.

Neurol Sci 42 （ 8 ） 3471 - 3474 2021年08月

ISSN  1590-1874

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パーキンソン病患者を対象とした新型コロナウイルス感染拡大に関するアンケート(第2報)

手塚, 俊樹, 長田, 高志, 寺山, 靖夫, 窪田, 真人, 大草, 翔平, 鈴木, 則宏, 久保, 紳一郎, 椎橋, 元, 中原, 仁 and 関, 守信

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   80 2021年07月

A case of progressive supranuclear palsy with predominant cerebellar ataxia diagnosed by [(18)F]PM-PBB3 tau PET

Ishizuchi, K., Takizawa, T., Tezuka, T., Takahata, K., Seki, M., Tabuchi, H., Ueda, R., Kubota, M., Mimura, M., Nakahara, J. and Ito, D.

J Neurol Sci 425   117440 2021年06月

ISSN  0022-510x

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【脳神経-もう一度眺めてみよう】機能と障害　第XII脳神経(舌下神経)hypoglossal nerve

手塚, 俊樹 and 滝沢, 翼

Clinical Neuroscience 39 （ 5 ） 571 - 573 2021年05月

ISSN  0289-0585

【タウPET:その足跡と今】アルツハイマー病におけるタウPETイメージング

手塚, 俊樹 and 伊東, 大介

臨床放射線 66 （ 4 ） 327 - 334 2021年04月

ISSN  0009-9252

【Neuro-COVID-19】COVID-19の神経障害　頭痛・筋痛

滝沢, 翼, 手塚, 俊樹 and 鈴木, 則宏

Clinical Neuroscience 39 （ 3 ） 327 - 330 2021年03月

ISSN  0289-0585

【COVID-19と神経治療学】COVID-19に合併する神経症候

手塚, 俊樹 and 中原, 仁

神経治療学 38 （ 1 ） 7 - 13 2021年01月

ISSN  0916-8443

Evaluation of [(18)F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies

Tezuka, T., Takahata, K., Seki, M., Tabuchi, H., Momota, Y., Shiraiwa, M., Suzuki, N., Morimoto, A., Nakahara, T., Iwabuchi, Y., Miura, E., Yamamoto, Y., Sano, Y., Funaki, K., Yamagata, B., Ueda, R., Yoshizaki, T., Mashima, K., Shibata, M., Oyama, M., Okada, K., Kubota, M., Okita, H., Takao, M., Jinzaki, M., Nakahara, J., Mimura, M. and Ito, D.

Brain Commun 3 （ 4 ） fcab190 2021年

ISSN  2632-1297

　概要を見る

Tau aggregates represent a key pathologic feature of Alzheimer's disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer's disease tauopathies. The novel tau PET tracer, [(18)F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer's disease and non-Alzheimer's disease tauopathies. To assess the ability of [(18)F]PI-2620 to detect regional tau burden in non-Alzheimer's disease tauopathies compared with Alzheimer's disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer's disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [(18)F]PI-2620 PET (Image acquisition at 60-90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [(18)F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [(18)F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer's disease, focal retention of [(18)F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer's disease tauopathies had elevated [(18)F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer's disease, but not healthy controls. A head-to-head comparison of [(18)F]PI-2620 and [(18)F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer's disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [(18)F]PI-2620 retention in vivo. High [(18)F]PI-2620 uptake at 60-90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer's disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer's disease-tau aggregation. However, late acquisition PET images of [(18)F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer's disease-detectable tau radiotracer, [(18)F]PM-PBB3. A recent study reported that [(18)F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer's disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.

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磁化率強調画像におけるswallow tail signのパーキンソン病診断における有用性

関, 守信, 上田, 亮, 手塚, 俊樹, 馬島, 恭子, 吉崎, 崇仁 and 中原, 仁

臨床神経学 60 （ Suppl. ） S407 2020年11月

ISSN  0009-918X

網膜片頭痛様の症状を呈したEvans症候群の1例

手塚, 俊樹, 柴田, 護, 伊澤, 良兼, 菊池, 拓, 藤原, 広和, 秋野, 邦彦, 小沢, 洋子, 中原, 仁 and 滝沢, 翼

日本頭痛学会誌 47 （ 2 ） O2 - 2 2020年11月

ISSN  1345-6547

髄液中の抗原、PCR検査で診断に至ったアスペルギルス髄膜炎の1例

寺山, 千夏, 勝又, 雅裕, 関口, 耕史, 手塚, 俊樹, 伊達, 悠岳, 阿部, 雅広 and 中原, 仁

日本内科学会関東地方会 662回   57 2020年09月

Novel tau tracer, PI 2620, for Alzheimer's disease(AD) and non-AD tauopathies

手塚, 俊樹, 高畑, 圭輔, 関, 守信, 田渕, 肇, 上田, 亮, 馬島, 恭子, 大山, 宗徳, 岡田, 健祐, 船木, 桂, 山縣, 文, 吉崎, 崇仁, 中原, 理紀, 百田, 友紀, 白岩, 美花, 柴田, 護, 三浦, 瑛祐, 陣崎, 雅弘, 中原, 仁, 三村, 將 and 伊東, 大介

Dementia Japan 33 （ 4 ） 513 2019年10月

ISSN  1342-646X

磁化率強調画像におけるswallow tail signのパーキンソン病及び関連疾患診断における有用性

関, 守信, 上田, 亮, 手塚, 俊樹, 岡田, 健佑, 馬島, 恭子, 吉崎, 崇仁 and 中原, 仁

神経治療学 36 （ 6 ） S262 2019年10月

ISSN  0916-8443

【認知症早期診断・発症進行予防とリハビリテーション】認知症・神経変性疾患診療における次世代タウPETプローブの可能性　プロティノパチーイメージングの時代を迎えて

伊東, 大介 and 手塚, 俊樹

MEDICAL REHABILITATION  （ 241 ） 18 - 21 2019年10月

ISSN  1346-0773

　概要を見る

近年の病理学、分子遺伝学の発展により、ほとんどの神経変性疾患は、特定の蛋白質が障害部位に異常蓄積するプロティノパチーとして理解されるようになった。異常蛋白質の蓄積は、病態メカニズムの理解だけでなく診断、治療においても重要なターゲットとなっている。それまで構造画像と機能画像に頼られていた神経変性疾患のイメージング技術は、2004年にピッツバーグ大学のKlunkらにより報告されたアミロイドイメージングによりプロティノパチーイメージングの時代となった。さらに、Maruyamaらの報告を皮切りに、我が国を含めた技術開発によりタウ病変の画像化も可能となり、多種にわたるタウオパチーの精度の高い診断、鑑別が可能となりつつある。本稿では、タウオパチー診療におけるタウPETプローブの現状と可能性について論ずる。(著者抄録)

パーキンソン病患者におけるパレイドリアは認知症の指標になる可能性がある

馬島, 恭子, 長田, 高志, 吉崎, 崇仁, 渡邊, 由里香, 野口, 恵理, 谷川, 万里子, 大山, 宗徳, 手塚, 俊樹, 岡田, 健佑, 中原, 仁 and 関, 守信

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 13回   121 2019年07月

パーキンソン病患者における睡眠障害と覚醒障害の包括的検討

関, 守信, 長田, 高志, 吉崎, 崇仁, 谷川, 万里子, 野口, 恵理, 馬島, 恭子, 大山, 宗徳, 岡田, 健佑, 手塚, 俊樹 and 中原, 仁

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 13回   121 2019年07月

Modeling neurological diseases with induced pluripotent cells reprogrammed from immortalized lymphoblastoid cell lines

Fujimori, K., Tezuka, T., Ishiura, H., Mitsui, J., Doi, K., Yoshimura, J., Tada, H., Matsumoto, T., Isoda, M., Hashimoto, R., Hattori, N., Takahashi, T., Morishita, S., Tsuji, S., Akamatsu, W. and Okano, H.

Mol Brain 9 （ 1 ） 88 2016年10月

ISSN  1756-6606

　概要を見る

Patient-specific induced pluripotent stem cells (iPSCs) facilitate understanding of the etiology of diseases, discovery of new drugs and development of novel therapeutic interventions. A frequently used starting source of cells for generating iPSCs has been dermal fibroblasts (DFs) isolated from skin biopsies. However, there are also numerous repositories containing lymphoblastoid B-cell lines (LCLs) generated from a variety of patients. To date, this rich bioresource of LCLs has been underused for generating iPSCs, and its use would greatly expand the range of targeted diseases that could be studied by using patient-specific iPSCs. However, it remains unclear whether patient's LCL-derived iPSCs (LiPSCs) can function as a disease model. Therefore, we generated Parkinson's disease patient-specific LiPSCs and evaluated their utility as tools for modeling neurological diseases. We established iPSCs from two LCL clones, which were derived from a healthy donor and a patient carrying PARK2 mutations, by using existing non-integrating episomal protocols. Whole genome sequencing (WGS) and comparative genomic hybridization (CGH) analyses showed that the appearance of somatic variations in the genomes of the iPSCs did not vary substantially according to the original cell types (LCLs, T-cells and fibroblasts). Furthermore, LiPSCs could be differentiated into functional neurons by using the direct neurosphere conversion method (dNS method), and they showed several Parkinson's disease phenotypes that were similar to those of DF-iPSCs. These data indicate that the global LCL repositories can be used as a resource for generating iPSCs and disease models. Thus, LCLs are the powerful tools for generating iPSCs and modeling neurological diseases.

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糖尿病性下肢壊疽を来たし、腸腰筋膿瘍から敗血症性ショックを来した1例

手塚, 俊樹, 細谷, 幸司, 安田, 聖一, 日比野, 祐香, 小松, 素明, 加藤, 優子 and 竜崎, 崇和

日本透析医学会雑誌 49 （ Suppl.1 ） 440 2016年05月

ISSN  1340-3451