published_papers "タイトル(日本語)","タイトル(英語)","著者(日本語)","著者(英語)","担当区分","概要(日本語)","概要(英語)","出版者・発行元(日本語)","出版者・発行元(英語)","出版年月","誌名(日本語)","誌名(英語)","巻","号","開始ページ","終了ページ","記述言語","査読の有無","招待の有無","掲載種別","国際・国内誌","国際共著","DOI","ISSN","eISSN","URL","URL2","主要な業績かどうか","公開の有無" "Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.","Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey.","Naoko Matsui, Keiko Tanaka, Mitsuyo Ishida, Yohei Yamamoto, Yuri Matsubara, Reiko Saika, Takahiro Iizuka, Koshi Nakamura, Nagato Kuriyama, Makoto Matsui, Kokichi Arisawa, Yosikazu Nakamura, Ryuji Kaji, Satoshi Kuwabara, Yuishin Izumi","Naoko Matsui, Keiko Tanaka, Mitsuyo Ishida, Yohei Yamamoto, Yuri Matsubara, Reiko Saika, Takahiro Iizuka, Koshi Nakamura, Nagato Kuriyama, Makoto Matsui, Kokichi Arisawa, Yosikazu Nakamura, Ryuji Kaji, Satoshi Kuwabara, Yuishin Izumi","null","This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.","This study provides the current epidemiologic and clinical status of SPS in Japan. The symptom onset to the diagnosis of SPS was longer in patients with high-titer GAD65 antibodies than in those with low-titer GAD65 antibodies. The outcome of patients with SPS was generally favorable, but more aggressive immunotherapies are necessary for GAD65-positive patients with SPS.","null","null","2023-09-22","Neurology® Neuroimmunology & Neuroinflammation","Neurology® Neuroimmunology & Neuroinflammation","Vol.10","No.6","e200165","e200165","eng","true","null","scientific_journal","null","null","10.1212/NXI.0000000000200165","2332-7812","null","null","null","null","null" "Segmental Zoster Paresis Accompanied by Horner's Syndrome.","Segmental Zoster Paresis Accompanied by Horner's Syndrome.","Kenta Hanada, Yusuke Osaki, Koji Fujita, Tatsuya Fukumoto, Koji Fukushima, Hideki Kito, Yuishin Izumi","Kenta Hanada, Yusuke Osaki, Koji Fujita, Tatsuya Fukumoto, Koji Fukushima, Hideki Kito, Yuishin Izumi","null","We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.","We herein report a 90-year-old immunocompromised woman who developed right upper limb weakness and right ptosis with a miotic pupil 1 week after oral therapy for zoster on the right T2 dermatome. The right pupil was dilated with instillation of 1% apraclonidine, indicating Horner's syndrome. The patient was treated with intravenous acyclovir and methylprednisolone. Focal weakness related to zoster, generally known as segmental zoster paresis, improved over five months, but Horner's syndrome remained. We suggest that aggressive intravenous treatment should be considered for rare cases of zoster that occur with a combination of these two neurological conditions.","null","null","2023-09-15","Internal Medicine","Internal Medicine","Vol.62","No.18","2743","2746","eng","true","null","scientific_journal","null","null","10.2169/internalmedicine.0578-22","1349-7235","null","null","null","null","null" "The necessity to improve disaster preparedness among patients with amyotrophic lateral sclerosis and their families.","The necessity to improve disaster preparedness among patients with amyotrophic lateral sclerosis and their families.","Takehisa Hirayama, Mari Shibukawa, Harumi Morioka, Masamichi Hozumi, Hiroshi Tsuda, Naoki Atsuta, Yuishin Izumi, Yuki Nakayama, Toshio Shimizu, Haruhisa Inoue, Makoto Urushitani, Koji Yamanaka, Masashi Aoki, Satoru Ebihara, Atsushi Takeda, Osamu Kano","Takehisa Hirayama, Mari Shibukawa, Harumi Morioka, Masamichi Hozumi, Hiroshi Tsuda, Naoki Atsuta, Yuishin Izumi, Yuki Nakayama, Toshio Shimizu, Haruhisa Inoue, Makoto Urushitani, Koji Yamanaka, Masashi Aoki, Satoru Ebihara, Atsushi Takeda, Osamu Kano","null","Disaster preparation is an important issue for patients with amyotrophic lateral sclerosis (ALS). However, to the best of our knowledge, no studies have investigated disaster preparedness among patients with ALS. In this study, we aimed to investigate disaster preparation in patients with ALS and their caregivers, including their families, in Japan. We conducted a nationwide webinar in September 2022 titled ""ALS Café"" and distributed a self-report questionnaire to participants with questions about awareness of disaster preparedness, social countermeasures, stockpiles, and electricity demand. Forty-eight patients with ALS (27 male; average age 60.0 ± 9.3 years) and 23 caregivers (8 male; 55.7 ± 9.9 years) responded. The median revised ALS Functional Rating Scale score was 30.5, and 25% of the patients with ALS were on a ventilator. More than 70% of the respondents answered that they were not prepared for disasters, increasing to 89% in patients not using ventilators. In the event of their phones being down, 86% of the respondents had no plans for alternative means of communication. <30% of the respondents, including ventilator users, had secured human resources for transportation. Twenty-five percent of the respondents did not stockpile food and beverages, and 12% of the ventilator users had no government-recommended ventilator preparation equipment. Thus, although patients with ALS and their families with ventilators have a high awareness of disaster preparedness, their awareness remains insufficient. Furthermore, patients with ALS and their families without ventilators have a low awareness of disaster preparedness. Therefore, better education regarding disaster preparedness is necessary for these groups.","Disaster preparation is an important issue for patients with amyotrophic lateral sclerosis (ALS). However, to the best of our knowledge, no studies have investigated disaster preparedness among patients with ALS. In this study, we aimed to investigate disaster preparation in patients with ALS and their caregivers, including their families, in Japan. We conducted a nationwide webinar in September 2022 titled ""ALS Café"" and distributed a self-report questionnaire to participants with questions about awareness of disaster preparedness, social countermeasures, stockpiles, and electricity demand. Forty-eight patients with ALS (27 male; average age 60.0 ± 9.3 years) and 23 caregivers (8 male; 55.7 ± 9.9 years) responded. The median revised ALS Functional Rating Scale score was 30.5, and 25% of the patients with ALS were on a ventilator. More than 70% of the respondents answered that they were not prepared for disasters, increasing to 89% in patients not using ventilators. In the event of their phones being down, 86% of the respondents had no plans for alternative means of communication. <30% of the respondents, including ventilator users, had secured human resources for transportation. Twenty-five percent of the respondents did not stockpile food and beverages, and 12% of the ventilator users had no government-recommended ventilator preparation equipment. Thus, although patients with ALS and their families with ventilators have a high awareness of disaster preparedness, their awareness remains insufficient. Furthermore, patients with ALS and their families without ventilators have a low awareness of disaster preparedness. Therefore, better education regarding disaster preparedness is necessary for these groups.","null","null","2023-08","Journal of Clinical Neuroscience","Journal of Clinical Neuroscience","Vol.116","null","87","92","eng","true","null","scientific_journal","null","null","10.1016/j.jocn.2023.08.002","1532-2653","null","null","null","null","null" "Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases.","Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases.","Yuki Yamamoto, Nobuaki Yamamoto, Tomohiro Matsuda, Kazutaka Kuroda, Izumi Yamaguchi, Shu Sogabe, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Yuishin Izumi","Yuki Yamamoto, Nobuaki Yamamoto, Tomohiro Matsuda, Kazutaka Kuroda, Izumi Yamaguchi, Shu Sogabe, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yasushi Takagi, Yuishin Izumi","null","In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.","In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.","null","null","2023-08-04","Surgical Neurology International","Surgical Neurology International","Vol.14","null","274","274","eng","true","null","scientific_journal","null","null","10.25259/SNI_513_2023","2229-5097","null","null","null","null","null" "Cranial geometry in patients with dystonia and Parkinson's disease.","Cranial geometry in patients with dystonia and Parkinson's disease.","Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto, Yasushi Takagi","Joji Fujikawa, Ryoma Morigaki, Kazuhisa Miyake, Taku Matsuda, Hiroshi Koyama, Teruo Oda, Nobuaki Yamamoto, Yuishin Izumi, Hideo Mure, Satoshi Goto, Yasushi Takagi","null","Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.","Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.","null","null","2023-07-07","Scientific Reports","Scientific Reports","Vol.13","No.1","null","null","eng","true","null","scientific_journal","null","null","10.1038/s41598-023-37833-3","2045-2322","null","null","null","null","null" "CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.","CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis.","Kodai Kume, Takashi Kurashige, Keiko Muguruma, Hiroyuki Morino, Yui Tada, Mai Kikumoto, Tatsuo Miyamoto, Natsuko Silvia Akutsu, Yukiko Matsuda, Shinya Matsuura, Masahiro Nakamori, Ayumi Nishiyama, Rumiko Izumi, Tetsuya Niihori, Masashi Ogasawara, Nobuyuki Eura, Tamaki Kato, Mamoru Yokomura, Yoshiaki Nakayama, Hidefumi Ito, Masataka Nakamura, Kayoko Saito, Yuichi Riku, Yasushi Iwasaki, Hirofumi Maruyama, Yoko Aoki, Ichizo Nishino, Yuishin Izumi, Masashi Aoki, Hideshi Kawakami","Kodai Kume, Takashi Kurashige, Keiko Muguruma, Hiroyuki Morino, Yui Tada, Mai Kikumoto, Tatsuo Miyamoto, Natsuko Silvia Akutsu, Yukiko Matsuda, Shinya Matsuura, Masahiro Nakamori, Ayumi Nishiyama, Rumiko Izumi, Tetsuya Niihori, Masashi Ogasawara, Nobuyuki Eura, Tamaki Kato, Mamoru Yokomura, Yoshiaki Nakayama, Hidefumi Ito, Masataka Nakamura, Kayoko Saito, Yuichi Riku, Yasushi Iwasaki, Hirofumi Maruyama, Yoko Aoki, Ichizo Nishino, Yuishin Izumi, Masashi Aoki, Hideshi Kawakami","null","Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.","Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of motor neurons. Although repeat expansion in C9orf72 is its most common cause, the pathogenesis of ALS isn't fully clear. In this study, we show that repeat expansion in LRP12, a causative variant of oculopharyngodistal myopathy type 1 (OPDM1), is a cause of ALS. We identify CGG repeat expansion in LRP12 in five families and two simplex individuals. These ALS individuals (LRP12-ALS) have 61-100 repeats, which contrasts with most OPDM individuals with repeat expansion in LRP12 (LRP12-OPDM), who have 100-200 repeats. Phosphorylated TDP-43 is present in the cytoplasm of iPS cell-derived motor neurons (iPSMNs) in LRP12-ALS, a finding that reproduces the pathological hallmark of ALS. RNA foci are more prominent in muscle and iPSMNs in LRP12-ALS than in LRP12-OPDM. Muscleblind-like 1 aggregates are observed only in OPDM muscle. In conclusion, CGG repeat expansions in LRP12 cause ALS and OPDM, depending on the length of the repeat. Our findings provide insight into the repeat length-dependent switching of phenotypes.","null","null","2023-06-09","American Journal of Human Genetics","American Journal of Human Genetics","Vol.110","No.7","1086","1097","eng","true","null","scientific_journal","null","null","10.1016/j.ajhg.2023.05.014","1537-6605","null","null","null","null","null" "Autosomal Recessive Spinocerebellar Ataxia Type 9 With a Response to Phosphate Repletion: A Case Report.","Autosomal Recessive Spinocerebellar Ataxia Type 9 With a Response to Phosphate Repletion: A Case Report.","Shotaro Haji, Ryosuke Miyamoto, Hiroyuki Morino, Yusuke Osaki, Seijiro Tsuji, Ichizo Nishino, Masahiro Abe, Yuishin Izumi","Shotaro Haji, Ryosuke Miyamoto, Hiroyuki Morino, Yusuke Osaki, Seijiro Tsuji, Ichizo Nishino, Masahiro Abe, Yuishin Izumi","null","This provides Class IV evidence. This is a single observational study without controls.","This provides Class IV evidence. This is a single observational study without controls.","null","null","2023-05-09","Neurology. Genetics","Neurology. Genetics","Vol.9","No.3","null","null","eng","true","null","scientific_journal","null","null","10.1212/NXG.0000000000200070","2376-7839","null","null","null","null","null" "Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and verification in iPSC-derived motor neurons from patients","Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and verification in iPSC-derived motor neurons from patients","R Nakamura, G Tohnai, M Nakatochi, N Atsuta, H Watanabe, D Ito, M Katsuno, A Hirakawa, Yuishin Izumi, M Morita, T Hirayama, O Kano, K Kanai, N Hattori, A Taniguchi, N Suzuki, M Aoki, I Iwata, I Yabe, K Shibuya, S Kuwabara, M Oda, R Hashimoto, I Aiba, T Ishihara, O Onodera, T Yamashita, K Abe, K Mizoguchi, T Shimizu, Y Ikeda, T Yokota, K Hasegawa, F Tanaka, K Nakashima, Ryuji Kaji, JI Niwa, M Doyu, C Terao, S Ikegawa, K Fujimori, S Nakamura, F Ozawa, S Morimoto, K Onodera, T Ito, Y Okada, H Okano, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS) study group","R Nakamura, G Tohnai, M Nakatochi, N Atsuta, H Watanabe, D Ito, M Katsuno, A Hirakawa, Yuishin Izumi, M Morita, T Hirayama, O Kano, K Kanai, N Hattori, A Taniguchi, N Suzuki, M Aoki, I Iwata, I Yabe, K Shibuya, S Kuwabara, M Oda, R Hashimoto, I Aiba, T Ishihara, O Onodera, T Yamashita, K Abe, K Mizoguchi, T Shimizu, Y Ikeda, T Yokota, K Hasegawa, F Tanaka, K Nakashima, Ryuji Kaji, JI Niwa, M Doyu, C Terao, S Ikegawa, K Fujimori, S Nakamura, F Ozawa, S Morimoto, K Onodera, T Ito, Y Okada, H Okano, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis research (JaCALS) study group","null","Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS. We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants. We used Cox proportional hazards regression analysis with an additive model adjusted for sex, age at onset and the first two principal components calculated from genotyped data to conduct a genome-wide association study. We further analysed messenger RNA (mRNA) and phenotype expression in motor neurons derived from induced pluripotent stem cells (iPSC-MNs) of patients with ALS. Three novel loci were significantly associated with the survival of patients with sporadic ALS- at 5q31.3 (rs11738209, HR=2.36 (95% CI, 1.77 to 3.15), p=4.85×10), at 7p21.3 (rs2354952, 1.38 (95% CI, 1.24 to 1.55), p=1.61×10) and at 12q13.3 (rs60565245, 2.18 (95% CI, 1.66 to 2.86), p=2.35×10). and variants were associated with decreased mRNA expression of each gene in iPSC-MNs and reduced in vitro survival of iPSC-MNs obtained from patients with ALS. The iPSC-MN in vitro survival was reduced when the expression of and was partially disrupted. The rs60565245 was not associated with mRNA expression. We identified three loci associated with the survival of patients with sporadic ALS, decreased mRNA expression of and and the viability of iPSC-MNs from patients. The iPSC-MN model reflects the association between patient prognosis and genotype and can contribute to target screening and validation for therapeutic intervention.","Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS. We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants. We used Cox proportional hazards regression analysis with an additive model adjusted for sex, age at onset and the first two principal components calculated from genotyped data to conduct a genome-wide association study. We further analysed messenger RNA (mRNA) and phenotype expression in motor neurons derived from induced pluripotent stem cells (iPSC-MNs) of patients with ALS. Three novel loci were significantly associated with the survival of patients with sporadic ALS- at 5q31.3 (rs11738209, HR=2.36 (95% CI, 1.77 to 3.15), p=4.85×10), at 7p21.3 (rs2354952, 1.38 (95% CI, 1.24 to 1.55), p=1.61×10) and at 12q13.3 (rs60565245, 2.18 (95% CI, 1.66 to 2.86), p=2.35×10). and variants were associated with decreased mRNA expression of each gene in iPSC-MNs and reduced in vitro survival of iPSC-MNs obtained from patients with ALS. The iPSC-MN in vitro survival was reduced when the expression of and was partially disrupted. The rs60565245 was not associated with mRNA expression. We identified three loci associated with the survival of patients with sporadic ALS, decreased mRNA expression of and and the viability of iPSC-MNs from patients. The iPSC-MN model reflects the association between patient prognosis and genotype and can contribute to target screening and validation for therapeutic intervention.","null","null","2023-05-04","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2022-330851","1468-330X","null","null","null","null","null" "Genome-wide association study identifies a new susceptibility locus in for Multiple System Atrophy.","Genome-wide association study identifies a new susceptibility locus in for Multiple System Atrophy.","Yasuo Nakahara, Jun Mitsui, Hidetoshi Date, Joyce Kristine Porto, Yasuhiro Hayashi, Atsushi Yamashita, Yoshio Kusakabe, Takashi Matsukawa, Hiroyuki Ishiura, Tsutomu Yasuda, Atsushi Iwata, Jun Goto, Yaeko Ichikawa, Yoshio Momose, Yuji Takahashi, Tatsushi Toda, Rikifumi Ohta, Jun Yoshimura, Shinichi Morishita, K Emil Gustavsson, Darren Christy, Melissa Maczis, J Matthew Farrer, Han-Joon Kim, Sung-Sup Park, Beomseok Jeon, Jin Zhang, Weihong Gu, W Sonja Scholz, B Andrew Singleton, Henry Houlden, Ichiro Yabe, Hidenao Sasaki, Masaaki Matsushima, Hiroshi Takashima, Akio Kikuchi, Masashi Aoki, Kenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Ken Yamamoto, Mihoko Shimada, Taku Miyagawa, Yosuke Kawai, Nao Nishida, Katsushi Tokunaga, Alexandra Dürr, Alexis Brice, Alessandro Filla, Thomas Klockgether, Ullrich Wüllner, M Caroline Tanner, A Walter Kukull, M-Y Virginia Lee, Eliezer Masliah, A Phillip Low, Paola Sandroni, Laurie Ozelius, Tatiana Foroud, Shoji Tsuji","Yasuo Nakahara, Jun Mitsui, Hidetoshi Date, Joyce Kristine Porto, Yasuhiro Hayashi, Atsushi Yamashita, Yoshio Kusakabe, Takashi Matsukawa, Hiroyuki Ishiura, Tsutomu Yasuda, Atsushi Iwata, Jun Goto, Yaeko Ichikawa, Yoshio Momose, Yuji Takahashi, Tatsushi Toda, Rikifumi Ohta, Jun Yoshimura, Shinichi Morishita, K Emil Gustavsson, Darren Christy, Melissa Maczis, J Matthew Farrer, Han-Joon Kim, Sung-Sup Park, Beomseok Jeon, Jin Zhang, Weihong Gu, W Sonja Scholz, B Andrew Singleton, Henry Houlden, Ichiro Yabe, Hidenao Sasaki, Masaaki Matsushima, Hiroshi Takashima, Akio Kikuchi, Masashi Aoki, Kenju Hara, Akiyoshi Kakita, Mitsunori Yamada, Hitoshi Takahashi, Osamu Onodera, Masatoyo Nishizawa, Hirohisa Watanabe, Mizuki Ito, Gen Sobue, Kinya Ishikawa, Hidehiro Mizusawa, Kazuaki Kanai, Satoshi Kuwabara, Kimihito Arai, Shigeru Koyano, Yoshiyuki Kuroiwa, Kazuko Hasegawa, Tatsuhiko Yuasa, Kenichi Yasui, Kenji Nakashima, Hijiri Ito, Yuishin Izumi, Ryuji Kaji, Takeo Kato, Susumu Kusunoki, Yasushi Osaki, Masahiro Horiuchi, Ken Yamamoto, Mihoko Shimada, Taku Miyagawa, Yosuke Kawai, Nao Nishida, Katsushi Tokunaga, Alexandra Dürr, Alexis Brice, Alessandro Filla, Thomas Klockgether, Ullrich Wüllner, M Caroline Tanner, A Walter Kukull, M-Y Virginia Lee, Eliezer Masliah, A Phillip Low, Paola Sandroni, Laurie Ozelius, Tatiana Foroud, Shoji Tsuji","null","To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association ( = 6.5 × 10 ) that was replicated in additional Japanese samples ( = 2.9 × 10 . OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data ( = 5.0 × 10 . Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples ( =0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.","To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association ( = 6.5 × 10 ) that was replicated in additional Japanese samples ( = 2.9 × 10 . OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data ( = 5.0 × 10 . Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples ( =0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.","null","null","2023-05-02","medRxiv : the preprint server for health sciences","medRxiv : the preprint server for health sciences","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1101/2023.05.02.23289328","null","null","null","null","null","null" "Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies","Correlation of muscle ultrasound with clinical and pathological findings in idiopathic inflammatory myopathies","Takeshi Yoshida, Hiroki Yamazaki, Y Nishimori, Naoko Takamatsu, Koji Fukushima, Yusuke Osaki, Y Taniguchi, T Nozaki, Y Kumon, J Albayda, I Nishino, Yuishin Izumi","Takeshi Yoshida, Hiroki Yamazaki, Y Nishimori, Naoko Takamatsu, Koji Fukushima, Yusuke Osaki, Y Taniguchi, T Nozaki, Y Kumon, J Albayda, I Nishino, Yuishin Izumi","null","In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.","In idiopathic inflammatory myopathies (IIMs), the change in muscle echogenicity and its histopathological basis are not well understood. We quantitatively measured muscle echogenicity in patients with IIMs and evaluated its correlation with disease activity and histopathological findings. This study involved patients with IIMs who underwent both ultrasonography (US) and muscle biopsy, as well as age- and sex-matched rheumatoid arthritis patients as inflammatory disease controls. On US, axial images of the right biceps brachii and vastus medialis were obtained. Standardized histopathological scoring was used to quantitatively measure each pathological domain. Forty-two patients (17 with inclusion body myositis [IBM] and 25 with IIMs other than IBM) and 25 controls were included. The muscle echo intensity (EI) of patients with IIMs was significantly higher than that of controls. Muscle EI showed significant correlations with creatine kinase (r = 0.66, p < .001) and muscle strength (r = -0.73, p < .0001) in patients with non-IBM IIMs. In patients with IBM, moderate correlation was found between muscle EI and quadriceps muscle strength (r = -0.53, p = .028). Histopathologically, the number of infiltrating CD3+ inflammatory cells correlated with muscle EI in the non-IBM group (r = 0.56, p = .017), but not in the IBM group. Muscle EI may be useful as a surrogate marker of muscle inflammation in non-IBM IIM. Increased muscle EI may be difficult to interpret in patients with long-standing IBM, which has advanced and complex histopathology.","null","null","2023-04-28","Muscle & Nerve","Muscle & Nerve","Vol.68","No.1","39","47","eng","true","null","scientific_journal","null","null","10.1002/mus.27833","1097-4598","null","null","null","null","null" "Far-field potential of the compound muscle action potential as a reliable marker in amyotrophic lateral sclerosis","Far-field potential of the compound muscle action potential as a reliable marker in amyotrophic lateral sclerosis","M Higashihara, Hiroki Yamazaki, Yuishin Izumi, M Kobayashi, Hiroyuki Nodera, C Oishi, A Iwata, S Murayama, Ryuji Kaji, M Sonoo","M Higashihara, Hiroki Yamazaki, Yuishin Izumi, M Kobayashi, Hiroyuki Nodera, C Oishi, A Iwata, S Murayama, Ryuji Kaji, M Sonoo","null","Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS. Patients with ALS and age-matched healthy controls were enrolled. We used a proximal reference (pref) in addition to the conventional distal reference (dref). Routine CMAP was recorded from the belly-dref lead and FFP-CMAP from the dref-pref lead for the ulnar and tibial nerves. Multiple point stimulation motor unit number estimation (MUNE) was also examined in the ulnar nerve. Inter-rater reproducibility was evaluated by two examiners, and some patients were followed up every 3 mo for 1 y. We tested 17 patients with ALS and 10 controls. The amplitudes of routine CMAP and FFP-CMAP in the ulnar and tibial nerves, and hypothenar MUNE value in the ulnar nerve were significantly decreased in ALS compared to controls. Ulnar FFP-CMAP achieved the highest inter-rater intraclass correlation coefficient (ICC) value (0.942) when compared with routine CMAP (0.880) and MUNE (0.839). The tibial FFP-CMAP had a higher ICC value (0.986) than the routine CMAP (0.697). In this way, the FFP-CMAP showed high inter-rater reproducibility because its shape was not much influenced by the electrode position. During 1-y follow-up, decline of CMAP, FFP, and MUNE showed significant correlations with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). The FFP-CMAP shows promise as a reliable marker for ALS.","Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS. Patients with ALS and age-matched healthy controls were enrolled. We used a proximal reference (pref) in addition to the conventional distal reference (dref). Routine CMAP was recorded from the belly-dref lead and FFP-CMAP from the dref-pref lead for the ulnar and tibial nerves. Multiple point stimulation motor unit number estimation (MUNE) was also examined in the ulnar nerve. Inter-rater reproducibility was evaluated by two examiners, and some patients were followed up every 3 mo for 1 y. We tested 17 patients with ALS and 10 controls. The amplitudes of routine CMAP and FFP-CMAP in the ulnar and tibial nerves, and hypothenar MUNE value in the ulnar nerve were significantly decreased in ALS compared to controls. Ulnar FFP-CMAP achieved the highest inter-rater intraclass correlation coefficient (ICC) value (0.942) when compared with routine CMAP (0.880) and MUNE (0.839). The tibial FFP-CMAP had a higher ICC value (0.986) than the routine CMAP (0.697). In this way, the FFP-CMAP showed high inter-rater reproducibility because its shape was not much influenced by the electrode position. During 1-y follow-up, decline of CMAP, FFP, and MUNE showed significant correlations with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). The FFP-CMAP shows promise as a reliable marker for ALS.","null","null","2023-04-22","Muscle & Nerve","Muscle & Nerve","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1002/mus.27829","1097-4598","null","null","null","null","null" "Long-sheath Introducer-assisted Revascularization (L-SHARE) Technique for Treating Large-vessel Occlusion by a Giant Clot","Long-sheath Introducer-assisted Revascularization (L-SHARE) Technique for Treating Large-vessel Occlusion by a Giant Clot","Nobuaki Yamamoto, Kazutaka Kuroda, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Kenji Shimada, Ryoma Morigaki, Yasuhisa Kanematsu, Yuishin Izumi, Yasushi Takagi","Nobuaki Yamamoto, Kazutaka Kuroda, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Kenji Shimada, Ryoma Morigaki, Yasuhisa Kanematsu, Yuishin Izumi, Yasushi Takagi","null","Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.","Revascularization for common carotid artery (CCA) occlusion might be difficult. We reported our strategy for revascularizing CCA occlusion by giant clots. A 94-year-old woman was transferred to our hospital because of right hemiparesis and aphasia. CCA occlusion and giant clots were detected on ultrasonography. We performed mechanical thrombectomy using a 9-Fr balloon-guiding catheter, stent retriever, and aspiration catheter through a 9-Fr long-sheath introducer [long-sheath introducer-assisted revascularization (L-SHARE) technique]. We successfully recanalized CCA occlusion using this method. The L-SHARE technique might be useful for recanalization of CCA occlusion.","null","null","2023-03-15","Internal Medicine","Internal Medicine","Vol.62","No.6","909","913","eng","true","null","scientific_journal","null","null","10.2169/internalmedicine.0089-22","0918-2918","null","null","null","null","null" "M1/precuneus ratio as a surrogate marker of upper motor neuron sign in ALS","M1/precuneus ratio as a surrogate marker of upper motor neuron sign in ALS","Wataru Sako, Shotaro Haji, Takashi Abe, Yusuke Osaki, Yuki Matsumoto, Masafumi Harada, Yuishin Izumi","Wataru Sako, Shotaro Haji, Takashi Abe, Yusuke Osaki, Yuki Matsumoto, Masafumi Harada, Yuishin Izumi","null","To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease-tracking biomarker for amyotrophic lateral sclerosis (ALS). In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/precuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04). The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.","To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease-tracking biomarker for amyotrophic lateral sclerosis (ALS). In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/precuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04). The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.","null","null","2023-02-15","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.445","null","120548","120548","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2023.120548","1878-5883","null","null","null","null","null" "An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study","An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study","Shotaro Haji, Koji Fujita, Ryosuke Oki, Yusuke Osaki, Ryosuke Miyamoto, Hiroyuki Morino, Seiichi Nagano, Naoki Atsuta, Yuki Kanazawa, Yuki Matsumoto, Atsuko Arisawa, Hisashi Kawai, Yasutaka Sato, Satoshi Sakaguchi, Kenta Yagi, Tatsuto Hamatani, Tatsuo Kagimura, Hiroaki Yanagawa, Hideki Mochizuki, Manabu Doyu, Gen Sobue, Masafumi Harada, Yuishin Izumi","Shotaro Haji, Koji Fujita, Ryosuke Oki, Yusuke Osaki, Ryosuke Miyamoto, Hiroyuki Morino, Seiichi Nagano, Naoki Atsuta, Yuki Kanazawa, Yuki Matsumoto, Atsuko Arisawa, Hisashi Kawai, Yasutaka Sato, Satoshi Sakaguchi, Kenta Yagi, Tatsuto Hamatani, Tatsuo Kagimura, Hiroaki Yanagawa, Hideki Mochizuki, Manabu Doyu, Gen Sobue, Masafumi Harada, Yuishin Izumi","null","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. This trial began data collection in September 2021 and is expected to be completed in October 2023. This study can provide useful data to understand the characteristics of EPI-589. Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. DERR1-10.2196/42032.","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2'-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. This trial began data collection in September 2021 and is expected to be completed in October 2023. This study can provide useful data to understand the characteristics of EPI-589. Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6. DERR1-10.2196/42032.","null","null","2023-01-30","JMIR Research Protocols","JMIR Research Protocols","Vol.12","null","e42032","e42032","eng","true","null","scientific_journal","null","null","10.2196/42032","1929-0748","null","null","null","null","null" "循環器病を防ぐために 徳島県循環器病推進計画の中での急性期脳卒中診療の取り組み","循環器病を防ぐために 徳島県循環器病推進計画の中での急性期脳卒中診療の取り組み","兼松 康久, 山口 泉, 石原 学, 曽我部 周, 宮本 健志, 高麗 雅章, 島田 健司, 黒田 一駿, 山本 雄貴, 山本 伸昭, 和泉 唯信, 髙木 康志","Yasuhisa Kanematsu, Izumi Yamaguchi, Manabu Ishihara, Shu Sogabe, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, KURODA Kazutaka, Yuki Yamamoto, Nobuaki Yamamoto, Yuishin Izumi, Yasushi Takagi","null","Cerebrovascular and cardiovascular disease are the main causes of death in Japan. The leading causes of the need for long-term care in Japan are also cerebrovascular and cardiovascular disease, which together account for more than one-fourth of the total. The Cerebrovascular and Cardiovascular Disease Control Act, of Japanese national law, was promulgated by a legislative act in 2018. On the basis of the Cerebrovascular and Cardiovascular Disease Control Act, the Ministry of Health, Labour and Welfare, Japan, published the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease (Japanese National Plan) in 2020. By the example of the Japanese National Plan, Tokushima prefecture established a cerebrovascular and cardiovascular disease countermeasure promotion plan to progress cerebrovascular and cardiovascular disease measures according to their own circumstances. One of the important measures of the plan is improving emergency transportation systems. Patients with intracranial large vessel occlusion strokes should be served by direct transfer to endovascular capable centers avoiding delays by misguided transfer to primary stroke centers. Considering the limited availability of endovascular capable centers, accurate identification of patients with high probability of having large vessel occlusion strokes in the prehospital setting is importance. To address this problem, we introduced prehospital scale called Field Assessment Stroke Triage for Emergency Destination (FAST-ED) on emergency transportation systems in Tokushima city.","Cerebrovascular and cardiovascular disease are the main causes of death in Japan. The leading causes of the need for long-term care in Japan are also cerebrovascular and cardiovascular disease, which together account for more than one-fourth of the total. The Cerebrovascular and Cardiovascular Disease Control Act, of Japanese national law, was promulgated by a legislative act in 2018. On the basis of the Cerebrovascular and Cardiovascular Disease Control Act, the Ministry of Health, Labour and Welfare, Japan, published the Japanese National Plan for Promotion of Measures Against Cerebrovascular and Cardiovascular Disease (Japanese National Plan) in 2020. By the example of the Japanese National Plan, Tokushima prefecture established a cerebrovascular and cardiovascular disease countermeasure promotion plan to progress cerebrovascular and cardiovascular disease measures according to their own circumstances. One of the important measures of the plan is improving emergency transportation systems. Patients with intracranial large vessel occlusion strokes should be served by direct transfer to endovascular capable centers avoiding delays by misguided transfer to primary stroke centers. Considering the limited availability of endovascular capable centers, accurate identification of patients with high probability of having large vessel occlusion strokes in the prehospital setting is importance. To address this problem, we introduced prehospital scale called Field Assessment Stroke Triage for Emergency Destination (FAST-ED) on emergency transportation systems in Tokushima city.","null","null","2022-12-25","四国医学雑誌","Shikoku Acta Medica","Vol.78","No.5-6","135","138","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/117958","null","null","null" "重症筋無力症との鑑別を要したクッシング病の1例","重症筋無力症との鑑別を要したクッシング病の1例","亀井 友志, 武藤 浩平, 山本 雄貴, 藤田 浩司, 和泉 唯信, 原 倫世","Yushi Kamei, MUTO Kohei, Yuki Yamamoto, Koji Fujita, Yuishin Izumi, Tomoyo Hara","null","The patient is a 77-year-old woman with a history of diabetes mellitus that was refractory to the medication and dietary restrictions. Four months prior to the admission, she developed a dropped head and ptosis that worsened in the evening. These symptoms were improved by the edrophonium test and the 3 Hz repetitive nerve stimulation testing was positive ; nevertheless, anti-acetylcholine and anti-muscle-specific tyrosine kinase antibodies were negative. Further examination demonstrated sustained hypokalemia and high levels of cortisol and ACTH. Moreover, CRH and high-dose dexamethasone suppression testings were positive and MRI demonstrated pituitary microadenoma. Based on these findings, she was subsequently diagnosed with Cushing's disease. After the resection of the pituitary tumor, ptosis improved with an alleviation of systemic edema, suggesting that it was caused by an eyelid edema. This case uniquely illustrates that Cushing's disease may mimic myasthenia gravis. Differentiation of the two disorders is crucial as treatment with steroids could compromise the interpretation of diagnostic testings for Cushing's disease and might result in a disease exacerbation. In this case, the history of treatment-refractory diabetes mellitus was helpful cue to differentiate the two disorders.","The patient is a 77-year-old woman with a history of diabetes mellitus that was refractory to the medication and dietary restrictions. Four months prior to the admission, she developed a dropped head and ptosis that worsened in the evening. These symptoms were improved by the edrophonium test and the 3 Hz repetitive nerve stimulation testing was positive ; nevertheless, anti-acetylcholine and anti-muscle-specific tyrosine kinase antibodies were negative. Further examination demonstrated sustained hypokalemia and high levels of cortisol and ACTH. Moreover, CRH and high-dose dexamethasone suppression testings were positive and MRI demonstrated pituitary microadenoma. Based on these findings, she was subsequently diagnosed with Cushing's disease. After the resection of the pituitary tumor, ptosis improved with an alleviation of systemic edema, suggesting that it was caused by an eyelid edema. This case uniquely illustrates that Cushing's disease may mimic myasthenia gravis. Differentiation of the two disorders is crucial as treatment with steroids could compromise the interpretation of diagnostic testings for Cushing's disease and might result in a disease exacerbation. In this case, the history of treatment-refractory diabetes mellitus was helpful cue to differentiate the two disorders.","null","null","2022-12-25","四国医学雑誌","Shikoku Acta Medica","Vol.78","No.5-6","221","226","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/117976","null","null","null" "低Na血症を合併した抗LGI1抗体陽性辺縁系脳炎の一例","低Na血症を合併した抗LGI1抗体陽性辺縁系脳炎の一例","松下 知樹, 笠井 嘉人, 新家 崇義, 原田 雅史, 武藤 浩平, 土師 正太郎, 和泉 唯信","MATSUSHITA Tomoki, Hiroto Kasai, Takayoshi Shinya, Masafumi Harada, MUTO Kohei, Shotaro Haji, Yuishin Izumi","null","null","null","null","null","2022-12","四国医学雑誌","Shikoku Acta Medica","Vol.78","No.5-6","246","247","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","null","null","null","null" "脳静脈洞血栓症に対して経皮的血栓回収術を行った3例","脳静脈洞血栓症に対して経皮的血栓回収術を行った3例","黒田 一駿, 山本 雄貴, 山本 伸昭, 和泉 唯信, 山口 泉, 島田 健司, 兼松 康久, 宮本 健志, 髙木 康志","KURODA Kazutaka, Yuki Yamamoto, Nobuaki Yamamoto, Yuishin Izumi, Izumi Yamaguchi, Kenji Shimada, Yasuhisa Kanematsu, Takeshi Miyamoto, Yasushi Takagi","null","null","null","null","null","2022-12","四国医学雑誌","Shikoku Acta Medica","Vol.78","No.5-6","221","226","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","null","null","null","null" "徳島市におけるアプリケーションを用いた脳主幹動脈閉塞診断スケールの活用,","徳島市におけるアプリケーションを用いた脳主幹動脈閉塞診断スケールの活用,","山本 雄貴, 山本 伸昭, 黒田 一駿, 和泉 唯信, 兼松 康久, 山口 泉, 曽我部 周, 高麗 雅章, 島田 健司, 髙木 康志","Yuki Yamamoto, Nobuaki Yamamoto, KURODA Kazutaka, Yuishin Izumi, Yasuhisa Kanematsu, Izumi Yamaguchi, Shu Sogabe, Masaaki Korai, Kenji Shimada, Yasushi Takagi","null","null","null","null","null","2022-12","四国医学雑誌","Shikoku Acta Medica","Vol.78","No.5,6","248","249","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","null","null","null","null" "Application of z-score-based quantification of muscle echogenicity for the diagnosis of sarcopenia in patients with rheumatoid arthritis","Application of z-score-based quantification of muscle echogenicity for the diagnosis of sarcopenia in patients with rheumatoid arthritis","Takeshi Yoshida, Y Kumon, N Takamatsu, T Nozaki, M Inoue, J Albayda, Yuishin Izumi","Takeshi Yoshida, Y Kumon, N Takamatsu, T Nozaki, M Inoue, J Albayda, Yuishin Izumi","null","null","null","null","null","2022-12","Geriatrics & Gerontology International","Geriatrics & Gerontology International","Vol.22","No.12","1055","1057","eng","true","null","scientific_journal","null","null","10.1111/ggi.14507","1447-0594","null","null","null","null","null" "Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy","Genetic and clinical landscape of childhood cerebellar hypoplasia and atrophy","M Sakamoto, K Iwama, M Sasaki, A Ishiyama, H Komaki, T Saito, E Takeshita, Y Shimizu-Motohashi, K Haginoya, T Kobayashi, T Goto, Y Tsuyusaki, M Iai, K Kurosawa, H Osaka, J Tohyama, Y Kobayashi, N Okamoto, Y Suzuki, S Kumada, K Inoue, H Mashimo, A Arisaka, I Kuki, H Saijo, K Yokochi, M Kato, Y Inaba, Y Gomi, S Saitoh, K Shirai, M Morimoto, Yuishin Izumi, Y Watanabe, SI Nagamitsu, Y Sakai, S Fukumura, K Muramatsu, T Ogata, K Yamada, K Ishigaki, K Hirasawa, K Shimoda, M Akasaka, K Kohashi, T Sakakibara, M Ikuno, N Sugino, T Yonekawa, S Gürsoy, T Cinleti, CA Kim, KW Teik, CM Yan, M Haniffa, C Ohba, S Ito, H Saitsu, K Saida, N Tsuchida, Y Uchiyama, E Koshimizu, A Fujita, K Hamanaka, K Misawa, S Miyatake, T Mizuguchi, N Miyake, N Matsumoto","M Sakamoto, K Iwama, M Sasaki, A Ishiyama, H Komaki, T Saito, E Takeshita, Y Shimizu-Motohashi, K Haginoya, T Kobayashi, T Goto, Y Tsuyusaki, M Iai, K Kurosawa, H Osaka, J Tohyama, Y Kobayashi, N Okamoto, Y Suzuki, S Kumada, K Inoue, H Mashimo, A Arisaka, I Kuki, H Saijo, K Yokochi, M Kato, Y Inaba, Y Gomi, S Saitoh, K Shirai, M Morimoto, Yuishin Izumi, Y Watanabe, SI Nagamitsu, Y Sakai, S Fukumura, K Muramatsu, T Ogata, K Yamada, K Ishigaki, K Hirasawa, K Shimoda, M Akasaka, K Kohashi, T Sakakibara, M Ikuno, N Sugino, T Yonekawa, S Gürsoy, T Cinleti, CA Kim, KW Teik, CM Yan, M Haniffa, C Ohba, S Ito, H Saitsu, K Saida, N Tsuchida, Y Uchiyama, E Koshimizu, A Fujita, K Hamanaka, K Misawa, S Miyatake, T Mizuguchi, N Miyake, N Matsumoto","null","Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.","Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.","null","null","2022-12","Genetics in Medicine","Genetics in Medicine","Vol.24","No.12","2453","2463","eng","true","null","scientific_journal","null","null","10.1016/j.gim.2022.08.007","1530-0366","null","null","null","null","null" "A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA.","A Pilot Study of A2NTX, a Novel Low-Molecular-Weight Neurotoxin Derived from Subtype A2 for Post-Stroke Lower Limb Spasticity: Comparison with OnabotulinumtoxinA.","Ryuji Kaji, Ai Miyashiro, Nori Sato, Taiki Furumoto, Toshiaki Takeuchi, Ryosuke Miyamoto, Tomoko Kohda, Yuishin Izumi, Shunji Kozaki","Ryuji Kaji, Ai Miyashiro, Nori Sato, Taiki Furumoto, Toshiaki Takeuchi, Ryosuke Miyamoto, Tomoko Kohda, Yuishin Izumi, Shunji Kozaki","null","= 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.","= 0.002), but was unaffected in the A2NTX-injected group by day 60, suggesting there was less spread of A2NTX to the upper limb than there was with BOTOX. Being a small-sized pilot investigation with an imbalance in the gender of the subjects, the present study suggested superior efficacy and safety of A2NTX, and warrants a larger scale clinical trial of A2NTX to confirm these preliminary results.","null","null","2022-10-28","Toxins","Toxins","Vol.14","No.11","null","null","eng","true","null","scientific_journal","null","null","10.3390/toxins14110739","2072-6651","null","null","null","null","null" "Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial","Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial","K Imamura, Yuishin Izumi, M Nagai, K Nishiyama, Y Watanabe, R Hanajima, N Egawa, T Ayaki, R Oki, Koji Fujita, R Uozumi, A Morinaga, T Hirohashi, Y Fujii, T Yamamoto, H Tatebe, T Tokuda, N Takahashi, S Morita, R Takahashi, H Inoue","K Imamura, Yuishin Izumi, M Nagai, K Nishiyama, Y Watanabe, R Hanajima, N Egawa, T Ayaki, R Oki, Koji Fujita, R Uozumi, A Morinaga, T Hirohashi, Y Fujii, T Yamamoto, H Tatebe, T Tokuda, N Takahashi, S Morita, R Takahashi, H Inoue","null","Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1-3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg-400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required. AMED and iPS Cell Research Fund.","Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1-3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg-400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required. AMED and iPS Cell Research Fund.","null","null","2022-10-25","eClinicalMedicine","eClinicalMedicine","Vol.53","null","101707","101707","eng","true","null","scientific_journal","null","null","10.1016/j.eclinm.2022.101707","2589-5370","null","null","null","null","null" "A case of anti-NT5c1A antibody-seropositive inclusion body myositis associated with severe dysphagia and prominent forearm weakness","A case of anti-NT5c1A antibody-seropositive inclusion body myositis associated with severe dysphagia and prominent forearm weakness","Naoko Matsui, Mika Takahara, Hiroki Yamazaki, Naoko Takamatsu, Yusuke Osaki, Ryuji Kaji, Ichizo Nishino, Satoshi Yamashita, Yuishin Izumi","Naoko Matsui, Mika Takahara, Hiroki Yamazaki, Naoko Takamatsu, Yusuke Osaki, Ryuji Kaji, Ichizo Nishino, Satoshi Yamashita, Yuishin Izumi","null","null","null","null","null","2022-10-24","Neurology and Clinical Neuroscience","Neurology and Clinical Neuroscience","Vol.11","No.1","46","48","eng","true","null","scientific_journal","null","null","10.1111/ncn3.12678","2049-4173","null","null","null","null","null" "The SYNGAP1 3'UTR variant in ALS patients causes aberrant SYNGAP1 splicing and dendritic spine loss by recruiting HNRNPK","The SYNGAP1 3'UTR variant in ALS patients causes aberrant SYNGAP1 splicing and dendritic spine loss by recruiting HNRNPK","S Yokoi, T Ito, K Sahashi, M Nakatochi, R Nakamura, G Tohnai, Y Fujioka, S Ishigaki, T Udagawa, Yuishin Izumi, M Morita, O Kano, M Oda, T Sone, H Okano, N Atsuta, M Katsuno, Y Okada, G Sobue","S Yokoi, T Ito, K Sahashi, M Nakatochi, R Nakamura, G Tohnai, Y Fujioka, S Ishigaki, T Udagawa, Yuishin Izumi, M Morita, O Kano, M Oda, T Sone, H Okano, N Atsuta, M Katsuno, Y Okada, G Sobue","null","Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 () mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform γ levels, which caused dendritic spine loss. Moreover, the variant excessively recruited FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK), and antisense oligonucleotides (ASOs) blocking HNRNPK altered aberrant splicing and ameliorated dendritic spine loss. These data suggest that excessive recruitment of RNA-binding proteins, especially HNRNPK, as well as changes in isoforms, are crucial for spine formation in motor neurons. It is not yet known which RNAs cause the pathogenesis of amyotrophic lateral sclerosis (ALS). We previously reported that Fused in sarcoma (FUS), a pathogenic RNA-binding protein in ALS, stabilizes synaptic Ras-GTPase activating protein 1 () mRNA at its 3' untranslated region (UTR) and maintains dendritic spine maturation. To elucidate whether this mechanism is crucial for ALS, we identified the 3'UTR variant rs149438267 at the FUS binding site. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the variant showed aberrant splicing, which caused dendritic spine loss along with excessive recruitment of FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK). Our findings that dendritic spine loss is because of excess recruitment of RNA-binding proteins provide a basis for the future exploration of ALS-related RNA-binding proteins.","Fused in sarcoma (FUS) is a pathogenic RNA-binding protein in amyotrophic lateral sclerosis (ALS). We previously reported that FUS stabilizes Synaptic Ras-GTPase activating protein 1 () mRNA at its 3' untranslated region (UTR) and maintains spine maturation. To elucidate the pathologic roles of this mechanism in ALS patients, we identified the 3'UTR variant rs149438267 in seven (four males and three females) out of 807 ALS patients at the FUS binding site from a multicenter cohort in Japan. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the variant showed aberrant splicing, increased isoform α1 levels, and decreased isoform γ levels, which caused dendritic spine loss. Moreover, the variant excessively recruited FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK), and antisense oligonucleotides (ASOs) blocking HNRNPK altered aberrant splicing and ameliorated dendritic spine loss. These data suggest that excessive recruitment of RNA-binding proteins, especially HNRNPK, as well as changes in isoforms, are crucial for spine formation in motor neurons. It is not yet known which RNAs cause the pathogenesis of amyotrophic lateral sclerosis (ALS). We previously reported that Fused in sarcoma (FUS), a pathogenic RNA-binding protein in ALS, stabilizes synaptic Ras-GTPase activating protein 1 () mRNA at its 3' untranslated region (UTR) and maintains dendritic spine maturation. To elucidate whether this mechanism is crucial for ALS, we identified the 3'UTR variant rs149438267 at the FUS binding site. Human-induced pluripotent stem cell (hiPSC)-derived motor neurons with the variant showed aberrant splicing, which caused dendritic spine loss along with excessive recruitment of FUS and heterogeneous nuclear ribonucleoprotein K (HNRNPK). Our findings that dendritic spine loss is because of excess recruitment of RNA-binding proteins provide a basis for the future exploration of ALS-related RNA-binding proteins.","null","null","2022-10-19","The Journal of Neuroscience","The Journal of Neuroscience","Vol.42","No.47","8881","8896","eng","true","null","scientific_journal","null","null","10.1523/JNEUROSCI.0455-22.2022","1529-2401","null","null","null","null","null" "Comparison of two families with and without ataxia harboring novel variants in PRKCG","Comparison of two families with and without ataxia harboring novel variants in PRKCG","Y Tada, K Kume, S Noguchi, T Sekiya, K Nishinaka, H Ishiguchi, J Koh, S Emori, Y Nakayama, T Kurashige, Yuishin Izumi, H Ito, N Sakai, H Kawakami","Y Tada, K Kume, S Noguchi, T Sekiya, K Nishinaka, H Ishiguchi, J Koh, S Emori, Y Nakayama, T Kurashige, Yuishin Izumi, H Ito, N Sakai, H Kawakami","null","Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant SCA caused by variants of the PRKCG encoding protein kinase C gamma (PKCγ). Although the toxic gain-of-function mechanism is the main cause of SCA14, its molecular pathophysiology remains unclear. To elucidate the molecular pathogenesis of SCA14, we analyzed two families with the variants in PRKCG. Clinical symptoms and neurological findings of two Japanese families were evaluated by neurologists. Exome sequencing was performed using the BGI platform. GFP-tagged PRKCGs harboring the identified variants were transfected into the HeLa cells, and aggregation of PKCγ was analyzed using confocal laser microscopy. Solubility of PKCγ was evaluated by assessing the proportion of insoluble fraction present in1% Triton-X. Patients in family 1 presented with only cerebellar atrophy without ataxia; however, patients in family 2 exhibited cerebellar ataxia, dystonia, and more severe cerebellar atrophy than those in family 1. Exome sequencing identified two novel missense variants of PRKCG:c.171 G > C,p.W57C (family 1), and c.400 T > C,p.C134R (family 2). Both the mutant PKCγ aggregated in the cytoplasm. Although the solubility of PKCγ of the C134R variant was lower than that of the wild-type, PKCγ of W57C retained its solubility. In conclusion, we identified two novel variants of PRKCG. The difference in severity between the two families may be due to the difference in solubility changes observed between the two variants. Decreased solubility of the PKCγ may play an important role in the pathogenesis of SCA14.","Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant SCA caused by variants of the PRKCG encoding protein kinase C gamma (PKCγ). Although the toxic gain-of-function mechanism is the main cause of SCA14, its molecular pathophysiology remains unclear. To elucidate the molecular pathogenesis of SCA14, we analyzed two families with the variants in PRKCG. Clinical symptoms and neurological findings of two Japanese families were evaluated by neurologists. Exome sequencing was performed using the BGI platform. GFP-tagged PRKCGs harboring the identified variants were transfected into the HeLa cells, and aggregation of PKCγ was analyzed using confocal laser microscopy. Solubility of PKCγ was evaluated by assessing the proportion of insoluble fraction present in1% Triton-X. Patients in family 1 presented with only cerebellar atrophy without ataxia; however, patients in family 2 exhibited cerebellar ataxia, dystonia, and more severe cerebellar atrophy than those in family 1. Exome sequencing identified two novel missense variants of PRKCG:c.171 G > C,p.W57C (family 1), and c.400 T > C,p.C134R (family 2). Both the mutant PKCγ aggregated in the cytoplasm. Although the solubility of PKCγ of the C134R variant was lower than that of the wild-type, PKCγ of W57C retained its solubility. In conclusion, we identified two novel variants of PRKCG. The difference in severity between the two families may be due to the difference in solubility changes observed between the two variants. Decreased solubility of the PKCγ may play an important role in the pathogenesis of SCA14.","null","null","2022-10","Journal of Human Genetics","Journal of Human Genetics","Vol.67","No.10","595","599","eng","true","null","scientific_journal","null","null","10.1038/s10038-022-01057-6","1435-232X","null","null","null","null","null" "Correction: Comparison of two families with and without ataxia harboring novel variants in PRKCG","Correction: Comparison of two families with and without ataxia harboring novel variants in PRKCG","Y Tada, K Kume, S Noguchi, T Sekiya, K Nishinaka, H Ishiguchi, J Koh, S Emori, Y Nakayama, T Kurashige, Yuishin Izumi, H Ito, N Sakai, H Kawakami","Y Tada, K Kume, S Noguchi, T Sekiya, K Nishinaka, H Ishiguchi, J Koh, S Emori, Y Nakayama, T Kurashige, Yuishin Izumi, H Ito, N Sakai, H Kawakami","null","null","null","null","null","2022-10","Journal of Human Genetics","Journal of Human Genetics","Vol.67","No.10","621","621","eng","true","null","scientific_journal","null","null","10.1038/s10038-022-01064-7","1435-232X","null","null","null","null","null" "Identification and validation of a gray matter volume network in Alzheimer's disease","Identification and validation of a gray matter volume network in Alzheimer's disease","M Chuluunbat, D Matsuda, Koji Fujita, M Otomo, Youichi Otomi, K Kudo, Masafumi Harada, Yuishin Izumi","M Chuluunbat, D Matsuda, Koji Fujita, M Otomo, Youichi Otomi, K Kudo, Masafumi Harada, Yuishin Izumi","null","This study aims to identify and validate a gray matter volume network in patients with Alzheimer's disease (AD). To identify a disease-related network, a principal component analysis-based algorithm, Scaled Subprofile Model, was applied to gray matter volume data derived from structural T1-weighted magnetic resonance imaging of the training sample that consisted of nine patients with AD (women, four; dementia, seven; mild cognitive impairment, two; age, 66.7 ± 8.8 [mean ± SD] years) with positive F-flutemetamol amyloid positron emission tomography and eight age-matched healthy controls obtained on-site. The network expression scores were calculated by topographic profile rating in the validation sample obtained via the Open Access Series of Imaging Studies and comprised 12 patients with AD dementia (women, four; age, 70.0 ± 3.7 years) and 12 age-matched healthy controls. A significant network from the training sample, for which subject expression differed between the groups (permutation test, P = 0.006; sensitivity and specificity, 100%; area under the curve, 1), was identified. This network was represented by the principal components 1, 2, and 3 and showed a relative decrease in the inferior parietal lobule including angular gyrus, inferior temporal gyrus, premotor cortex, amygdala, hippocampus, and precuneus. It significantly differed between the groups with a sensitivity, specificity, and area under the curve of 83%, 91%, and 0.85, respectively, in the validation sample (P = 0.003). An AD-related gray matter volume network that captured relevant regions was identified in amyloid positron emission tomography-positive patients and validated in an independent sample.","This study aims to identify and validate a gray matter volume network in patients with Alzheimer's disease (AD). To identify a disease-related network, a principal component analysis-based algorithm, Scaled Subprofile Model, was applied to gray matter volume data derived from structural T1-weighted magnetic resonance imaging of the training sample that consisted of nine patients with AD (women, four; dementia, seven; mild cognitive impairment, two; age, 66.7 ± 8.8 [mean ± SD] years) with positive F-flutemetamol amyloid positron emission tomography and eight age-matched healthy controls obtained on-site. The network expression scores were calculated by topographic profile rating in the validation sample obtained via the Open Access Series of Imaging Studies and comprised 12 patients with AD dementia (women, four; age, 70.0 ± 3.7 years) and 12 age-matched healthy controls. A significant network from the training sample, for which subject expression differed between the groups (permutation test, P = 0.006; sensitivity and specificity, 100%; area under the curve, 1), was identified. This network was represented by the principal components 1, 2, and 3 and showed a relative decrease in the inferior parietal lobule including angular gyrus, inferior temporal gyrus, premotor cortex, amygdala, hippocampus, and precuneus. It significantly differed between the groups with a sensitivity, specificity, and area under the curve of 83%, 91%, and 0.85, respectively, in the validation sample (P = 0.003). An AD-related gray matter volume network that captured relevant regions was identified in amyloid positron emission tomography-positive patients and validated in an independent sample.","null","null","2022-07-19","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.440","null","120344","120344","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2022.120344","1878-5883","null","null","null","null","null" "Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis","Ultrasound assessment of sarcopenia in patients with rheumatoid arthritis","Takeshi Yoshida, Y Kumon, N Takamatsu, T Nozaki, M Inoue, Hiroyuki Nodera, J Albayda, Yuishin Izumi","Takeshi Yoshida, Y Kumon, N Takamatsu, T Nozaki, M Inoue, Hiroyuki Nodera, J Albayda, Yuishin Izumi","null","To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.","To evaluate the efficacy of ultrasound (US) as a diagnostic tool for sarcopenia in patients with rheumatoid arthritis (RA). Female RA patients aged >50 years and matched controls were cross-sectionally assessed. Sarcopenia was diagnosed based on the 2019-updated Asian Working Group for Sarcopenia definition. The cross-sectional area (CSA) and echo intensity (EI) of the biceps brachii, rectus femoris, and EI of the vastus lateralis were examined bilaterally. Correction for subcutaneous fat and calculation of the recorrected EI (rcEI) were performed. We performed logistic regression using both muscle rcEI and CSA with receiver operating curve analysis to evaluate the discriminative performance per muscle group. Seventy-eight consecutive RA patients and 15 age-and sex-matched controls were assessed. Sarcopenia was diagnosed in 34 RA patients (43.6%). The rcEI of examined muscles were significantly higher, whereas CSA were significantly lower in sarcopenic RA patients than in non-sarcopenic patients and matched controls. The combined discriminative performance of rcEI and CSA was superior to those of rcEI or CSA alone. This study suggests the use of US for the diagnosis of sarcopenia in RA patients. The diagnostic performance increases when both echogenicity and CSA are considered together rather than individually.","null","null","2022-07-01","Modern Rheumatology","Modern Rheumatology","Vol.32","No.4","728","735","eng","true","null","scientific_journal","null","null","10.1093/mr/roab049","1439-7609","null","null","null","null","null" "TDP-43 Accumulation Within Intramuscular Nerve Bundles of Patients With Amyotrophic Lateral Sclerosis.","TDP-43 Accumulation Within Intramuscular Nerve Bundles of Patients With Amyotrophic Lateral Sclerosis.","Takashi Kurashige, Hiroyuki Morino, Tomomi Murao, Yuishin Izumi, Tomohito Sugiura, Kazuya Kuraoka, Hideshi Kawakami, Tsuyoshi Torii, Hirofumi Maruyama","Takashi Kurashige, Hiroyuki Morino, Tomomi Murao, Yuishin Izumi, Tomohito Sugiura, Kazuya Kuraoka, Hideshi Kawakami, Tsuyoshi Torii, Hirofumi Maruyama","null","Results of this dual case-control and retrospective cohort study suggest that axonal pTDP-43 accumulations may be characteristic for patients with ALS. As such findings precede clinical fulfillment of the Gold Coast criteria, TDP-43 in nerve bundles may be a novel diagnostic biomarker for ALS.","Results of this dual case-control and retrospective cohort study suggest that axonal pTDP-43 accumulations may be characteristic for patients with ALS. As such findings precede clinical fulfillment of the Gold Coast criteria, TDP-43 in nerve bundles may be a novel diagnostic biomarker for ALS.","null","null","2022-07-01","JAMA Neurology","JAMA Neurology","Vol.79","No.7","693","701","eng","true","null","scientific_journal","null","null","10.1001/jamaneurol.2022.1113","2168-6157","null","null","null","null","null" "Application of ultrasound in a case of eosinophilic fasciitis mimicking stiff-person syndrome","Application of ultrasound in a case of eosinophilic fasciitis mimicking stiff-person syndrome","Hiroki Yamazaki, Naoko Matsui, N Takamatsu, Takeshi Yoshida, Koji Fukushima, T Takata, Yusuke Osaki, K Tanaka, Y Kubo, Yuishin Izumi","Hiroki Yamazaki, Naoko Matsui, N Takamatsu, Takeshi Yoshida, Koji Fukushima, T Takata, Yusuke Osaki, K Tanaka, Y Kubo, Yuishin Izumi","null","Eosinophilic fasciitis (EF) is a rare disorder characterized by muscle stiffness mimicking other neuromuscular diseases. The diagnosis of EF is made on the basis of typical skin lesions. We report a case of a 36-year-old male patient with suspected stiff-person syndrome (SPS), who presented with progressive limb muscle stiffness and limited mobility of both wrists without obvious skin changes. Ultrasound revealed fascial thickening of bilateral upper and lower limb muscles and enlargement of hypoechoic tissues around the flexor digitorum tendons of the wrist. Skin and fascia biopsy confirmed the diagnosis of EF. Prednisolone therapy resulted in the improvement of muscle stiffness and tightness. Our findings suggest the need to consider connective tissue diseases such as EF in a patient with atypical features of SPS. Ultrasound is helpful for visualizing the causes of muscle stiffness and joint contractures in EF patients.","Eosinophilic fasciitis (EF) is a rare disorder characterized by muscle stiffness mimicking other neuromuscular diseases. The diagnosis of EF is made on the basis of typical skin lesions. We report a case of a 36-year-old male patient with suspected stiff-person syndrome (SPS), who presented with progressive limb muscle stiffness and limited mobility of both wrists without obvious skin changes. Ultrasound revealed fascial thickening of bilateral upper and lower limb muscles and enlargement of hypoechoic tissues around the flexor digitorum tendons of the wrist. Skin and fascia biopsy confirmed the diagnosis of EF. Prednisolone therapy resulted in the improvement of muscle stiffness and tightness. Our findings suggest the need to consider connective tissue diseases such as EF in a patient with atypical features of SPS. Ultrasound is helpful for visualizing the causes of muscle stiffness and joint contractures in EF patients.","null","null","2022-07","Neuromuscular Disorders","Neuromuscular Disorders","Vol.32","No.7","590","593","eng","true","null","scientific_journal","null","null","10.1016/j.nmd.2022.05.009","1873-2364","null","null","null","null","null" "Diagnosis and Treatment of Tremor in Parkinson's Disease Using Mechanical Devices","Diagnosis and Treatment of Tremor in Parkinson's Disease Using Mechanical Devices","J Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, H Nakanishi, T Oda, Yuishin Izumi, Yasushi Takagi","J Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, H Nakanishi, T Oda, Yuishin Izumi, Yasushi Takagi","null","Parkinsonian tremors are sometimes confused with essential tremors or other conditions. Recently, researchers conducted several studies on tremor evaluation using wearable sensors and devices, which may support accurate diagnosis. Mechanical devices are also commonly used to treat tremors and have been actively researched and developed. Here, we aimed to review recent progress and the efficacy of the devices related to Parkinsonian tremors. The PubMed and Scopus databases were searched for articles. We searched for ""Parkinson disease"" and ""tremor"" and ""device"". Eighty-six articles were selected by our systematic approach. Many studies demonstrated that the diagnosis and evaluation of tremors in patients with PD can be done accurately by machine learning algorithms. Mechanical devices for tremor suppression include deep brain stimulation (DBS), electrical muscle stimulation, and orthosis. In recent years, adaptive DBS and optimization of stimulation parameters have been studied to further improve treatment efficacy. Due to developments using state-of-the-art techniques, effectiveness in diagnosing and evaluating tremor and suppressing it using these devices is satisfactorily high in many studies. However, other than DBS, no devices are in practical use. To acquire high-level evidence, large-scale studies and randomized controlled trials are needed for these devices.","Parkinsonian tremors are sometimes confused with essential tremors or other conditions. Recently, researchers conducted several studies on tremor evaluation using wearable sensors and devices, which may support accurate diagnosis. Mechanical devices are also commonly used to treat tremors and have been actively researched and developed. Here, we aimed to review recent progress and the efficacy of the devices related to Parkinsonian tremors. The PubMed and Scopus databases were searched for articles. We searched for ""Parkinson disease"" and ""tremor"" and ""device"". Eighty-six articles were selected by our systematic approach. Many studies demonstrated that the diagnosis and evaluation of tremors in patients with PD can be done accurately by machine learning algorithms. Mechanical devices for tremor suppression include deep brain stimulation (DBS), electrical muscle stimulation, and orthosis. In recent years, adaptive DBS and optimization of stimulation parameters have been studied to further improve treatment efficacy. Due to developments using state-of-the-art techniques, effectiveness in diagnosing and evaluating tremor and suppressing it using these devices is satisfactorily high in many studies. However, other than DBS, no devices are in practical use. To acquire high-level evidence, large-scale studies and randomized controlled trials are needed for these devices.","null","null","2022-07","Life","Life","Vol.13","No.1","78","78","eng","true","null","scientific_journal","null","null","10.3390/life13010078","2075-1729","null","null","null","null","null" "脳神経疾患克服に向けた研究推進の提言2020,各論I(方法論別)","Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020","望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 髙橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会, 青木 吉嗣, 石浦 浩之, 和泉 唯信, 小池 春樹, 島田 斉, 髙橋 祐二, 徳田 隆彦, 中嶋 秀人, 波田野 琢, 三澤 園子, 渡辺 宏久","望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 髙橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会, 青木 吉嗣, 石浦 浩之, Yuishin Izumi, 小池 春樹, 島田 斉, 髙橋 祐二, 徳田 隆彦, 中嶋 秀人, 波田野 琢, 三澤 園子, 渡辺 宏久","null","null","null","null","null","2022-06-24","臨床神経学","Clinical Neurology","Vol.62","No.6","429","442","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.cn-001695","0009-918X","null","null","null","null","null" "脳神経疾患克服に向けた研究推進の提言2020,各論II(疾患群別)","Recommendations (Proposal) for promoting research for overcoming neurological diseases 2020","望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 髙橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会, 青木 吉嗣, 石浦 浩之, 和泉 唯信, 小池 春樹, 島田 斉, 髙橋 祐二, 徳田 隆彦, 中嶋 秀人, 波田野 琢, 三澤 園子, 渡辺 宏久","望月 秀樹, 青木 正志, 池中 建介, 井上 治久, 岩坪 威, 宇川 義一, 岡澤 均, 小野 賢二郎, 小野寺 理, 北川 一夫, 齊藤 祐子, 下畑 享良, 髙橋 良輔, 戸田 達史, 中原 仁, 松本 理器, 水澤 英洋, 三井 純, 村山 繁雄, 勝野 雅央, 日本神経学会将来構想委員会, 青木 吉嗣, 石浦 浩之, Yuishin Izumi, 小池 春樹, 島田 斉, 髙橋 祐二, 徳田 隆彦, 中嶋 秀人, 波田野 琢, 三澤 園子, 渡辺 宏久","null","null","null","null","null","2022-06-24","臨床神経学","Clinical Neurology","Vol.62","No.6","443","457","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.cn-001696","0009-918X","null","null","null","null","null" "Early diagnosis of amyotrophic lateral sclerosis based on fasciculations in muscle ultrasonography: A machine learning approach.","Early diagnosis of amyotrophic lateral sclerosis based on fasciculations in muscle ultrasonography: A machine learning approach.","Koji Fukushima, Naoko Takamatsu, Yuki Yamamoto, Hiroki Yamazaki, Takeshi Yoshida, Yusuke Osaki, Shotaro Haji, Koji Fujita, Kazuma Sugie, Yuishin Izumi","Koji Fukushima, Naoko Takamatsu, Yuki Yamamoto, Hiroki Yamazaki, Takeshi Yoshida, Yusuke Osaki, Shotaro Haji, Koji Fujita, Kazuma Sugie, Yuishin Izumi","null","We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS.","Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.","null","null","2022-06-17","Clinical Neurophysiology","Clinical Neurophysiology","Vol.140","null","136","144","eng","true","null","scientific_journal","null","null","10.1016/j.clinph.2022.06.005","1872-8952","null","null","null","null","null" "Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.","Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.","Ryosuke Oki, Yuishin Izumi, Koji Fujita, Ryosuke Miyamoto, Hiroyuki Nodera, Yasutaka Sato, Satoshi Sakaguchi, Hiroshi Nokihara, Kazuaki Kanai, Taiji Tsunemi, Nobutaka Hattori, Yuki Hatanaka, Masahiro Sonoo, Naoki Atsuta, Gen Sobue, Toshio Shimizu, Kazumoto Shibuya, Ken Ikeda, Osamu Kano, Kazuto Nishinaka, Yasuhiro Kojima, Masaya Oda, Kiyonobu Komai, Hitoshi Kikuchi, Nobuo Kohara, Makoto Urushitani, Yoshiaki Nakayama, Hidefumi Ito, Makiko Nagai, Kazutoshi Nishiyama, Daisuke Kuzume, Shun Shimohama, Takayoshi Shimohata, Koji Abe, Tomohiko Ishihara, Osamu Onodera, Sagiri Isose, Nobuyuki Araki, Mitsuya Morita, Kazuyuki Noda, Tatsushi Toda, Hirofumi Maruyama, Hirokazu Furuya, Satoshi Teramukai, Tatsuo Kagimura, Kensuke Noma, Hiroaki Yanagawa, Satoshi Kuwabara, Ryuji Kaji","Ryosuke Oki, Yuishin Izumi, Koji Fujita, Ryosuke Miyamoto, Hiroyuki Nodera, Yasutaka Sato, Satoshi Sakaguchi, Hiroshi Nokihara, Kazuaki Kanai, Taiji Tsunemi, Nobutaka Hattori, Yuki Hatanaka, Masahiro Sonoo, Naoki Atsuta, Gen Sobue, Toshio Shimizu, Kazumoto Shibuya, Ken Ikeda, Osamu Kano, Kazuto Nishinaka, Yasuhiro Kojima, Masaya Oda, Kiyonobu Komai, Hitoshi Kikuchi, Nobuo Kohara, Makoto Urushitani, Yoshiaki Nakayama, Hidefumi Ito, Makiko Nagai, Kazutoshi Nishiyama, Daisuke Kuzume, Shun Shimohama, Takayoshi Shimohata, Koji Abe, Tomohiko Ishihara, Osamu Onodera, Sagiri Isose, Nobuyuki Araki, Mitsuya Morita, Kazuyuki Noda, Tatsushi Toda, Hirofumi Maruyama, Hirokazu Furuya, Satoshi Teramukai, Tatsuo Kagimura, Kensuke Noma, Hiroaki Yanagawa, Satoshi Kuwabara, Ryuji Kaji","null","A total of 130 patients (mean [SD] age, 61.0 [11.7] years; 74 men [56.9%]) were randomly assigned to methylcobalamin or placebo (65 each). A total of 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Of these, 124 patients proceeded to the open-label extended period. The least square means difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (-2.66 vs -4.63; 95% CI, 0.44-3.50; P = .01). The incidence of adverse events was similar between the 2 groups.","ClinicalTrials.gov Identifier: NCT03548311.","null","null","2022-06-01","JAMA Neurology","JAMA Neurology","Vol.79","No.6","575","583","eng","true","null","scientific_journal","null","null","10.1001/jamaneurol.2022.0901","2168-6157","null","null","null","null","null" "TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2.","TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2.","Naohiro Egawa, Yuishin Izumi, Hidefumi Suzuki, Itaru Tsuge, Koji Fujita, Hitoshi Shimano, Keiichi Izumikawa, Nobuhiro Takahashi, Kayoko Tsukita, Takako Enami, Masahiro Nakamura, Akira Watanabe, Motoko Naitoh, Shigehiko Suzuki, Tsuneyoshi Seki, Kazuhiro Kobayashi, Tatsushi Toda, Ryuji Kaji, Ryosuke Takahashi, Haruhisa Inoue","Naohiro Egawa, Yuishin Izumi, Hidefumi Suzuki, Itaru Tsuge, Koji Fujita, Hitoshi Shimano, Keiichi Izumikawa, Nobuhiro Takahashi, Kayoko Tsukita, Takako Enami, Masahiro Nakamura, Akira Watanabe, Motoko Naitoh, Shigehiko Suzuki, Tsuneyoshi Seki, Kazuhiro Kobayashi, Tatsushi Toda, Ryuji Kaji, Ryosuke Takahashi, Haruhisa Inoue","null","Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.","Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.","null","null","2022-05-14","Scientific Reports","Scientific Reports","Vol.12","No.1","null","null","eng","true","null","scientific_journal","null","null","10.1038/s41598-022-12133-4","2045-2322","null","null","null","null","null" "Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis","Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis","G Tohnai, R Nakamura, N Atsuta, M Nakatochi, N Hayashi, D Ito, H Watanabe, H Watanabe, M Katsuno, Yuishin Izumi, A Taniguchi, K Kanai, M Morita, O Kano, S Kuwabara, M Oda, K Abe, M Aoki, I Aiba, K Okamoto, K Mizoguchi, T Ishihara, A Kawata, T Yokota, K Hasegawa, I Nagano, I Yabe, F Tanaka, S Kuru, N Hattori, K Nakashima, Ryuji Kaji, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)","G Tohnai, R Nakamura, N Atsuta, M Nakatochi, N Hayashi, D Ito, H Watanabe, H Watanabe, M Katsuno, Yuishin Izumi, A Taniguchi, K Kanai, M Morita, O Kano, S Kuwabara, M Oda, K Abe, M Aoki, I Aiba, K Okamoto, K Mizoguchi, T Ishihara, A Kawata, T Yokota, K Hasegawa, I Nagano, I Yabe, F Tanaka, S Kuru, N Hattori, K Nakashima, Ryuji Kaji, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)","null","DNAJC7 has recently been identified as an amyotrophic lateral sclerosis (ALS) gene via large-scale exome analysis, and its involvement in ALS is still unclear in various populations. This study aimed to determine the frequencies and characteristics of the DNAJC7 variants in a Japanese ALS cohort. A total of 807 unrelated Japanese patients with sporadic ALS were screened via exome analysis. In total, we detected six rare missense variants and one splice-site variant of the DNAJC7 gene, which are not reported in the Japanese public database. Furthermore, the missense variants are located around the TPR domain, which is important for the function of DNAJC7. The total frequency of the DNAJC7 variants in Japanese ALS patients was estimated at 0.87%. Collectively, these results suggest that variants of DNAJC7 are rare cause of Japanese patients with sporadic ALS.","DNAJC7 has recently been identified as an amyotrophic lateral sclerosis (ALS) gene via large-scale exome analysis, and its involvement in ALS is still unclear in various populations. This study aimed to determine the frequencies and characteristics of the DNAJC7 variants in a Japanese ALS cohort. A total of 807 unrelated Japanese patients with sporadic ALS were screened via exome analysis. In total, we detected six rare missense variants and one splice-site variant of the DNAJC7 gene, which are not reported in the Japanese public database. Furthermore, the missense variants are located around the TPR domain, which is important for the function of DNAJC7. The total frequency of the DNAJC7 variants in Japanese ALS patients was estimated at 0.87%. Collectively, these results suggest that variants of DNAJC7 are rare cause of Japanese patients with sporadic ALS.","null","null","2022-05","Neurobiology of Aging","Neurobiology of Aging","Vol.113","null","131","136","eng","true","null","scientific_journal","null","null","10.1016/j.neurobiolaging.2021.12.002","1558-1497","null","null","null","null","null" "Truncal dystonia with isolated middle cerebral artery ischemia: A case report of revascularization therapy for dystonia.","Truncal dystonia with isolated middle cerebral artery ischemia: A case report of revascularization therapy for dystonia.","Shinichi Matsumoto, Yuki Yamamoto, Koji Fujita, Ryosuke Miyamoto, Hidetaka Koizumi, Akihiro Tateishi, Naoaki Yamada, Yuishin Izumi","Shinichi Matsumoto, Yuki Yamamoto, Koji Fujita, Ryosuke Miyamoto, Hidetaka Koizumi, Akihiro Tateishi, Naoaki Yamada, Yuishin Izumi","null","Revascularization therapy improved CBF and truncal dystonia and could be a viable treatment option for dystonia with ischemia in the MCA region. Extensive cerebral ischemia can result in cortical inhibition loss or over-adapted cerebral plasticity and cause dystonia. Revascularization therapy may be useful for patients with dystonia and decreased CBF in the MCA region.","Revascularization therapy improved CBF and truncal dystonia and could be a viable treatment option for dystonia with ischemia in the MCA region. Extensive cerebral ischemia can result in cortical inhibition loss or over-adapted cerebral plasticity and cause dystonia. Revascularization therapy may be useful for patients with dystonia and decreased CBF in the MCA region.","null","null","2022-04-15","Surgical Neurology International","Surgical Neurology International","Vol.13","null","null","null","eng","true","null","scientific_journal","null","null","10.25259/SNI_173_2022","2229-5097","null","null","null","null","null" "Communicating the diagnosis: a survey of patients with amyotrophic lateral sclerosis and their families in Japan","Communicating the diagnosis: a survey of patients with amyotrophic lateral sclerosis and their families in Japan","T Hirayama, Yuishin Izumi, Y Nakayama, M Shibukawa, S Ebihara, O Kano","T Hirayama, Yuishin Izumi, Y Nakayama, M Shibukawa, S Ebihara, O Kano","null","To assess the needs of patients with amyotrophic lateral sclerosis (ALS) and their families when being communicated the diagnosis. We held a nationwide webinar in September 2020, titled ""ALS Café"", and distributed a self-report questionnaire to participants. This cross-sectional study included 56 respondents (patients, n = 32; family members, n = 24). Of the 56 respondents, 47 (84%) reported being anxious when they were communicated their diagnosis. The average time allocated for communicating the diagnosis was 36.3 ± 25.6 min, and 30% of respondents believed that insufficient time was allocated. Nearly half of the respondents were communicated their diagnosis by one physician, and 57% of the respondents received their diagnosis in one session. Approximately 80% of respondents received information about ventilators when they were being communicated their diagnosis, but most patients did not want to receive this information at that time. The anxious group tended to answer that the time to communicate the diagnosis was short. Meanwhile, all respondents in the mildly anxious group were provided with one or more information about the supportive contents along with the diagnosis. Moreover, in Japan, many patients with ALS and their families desire the legalization of euthanasia, which might affect decision-making. This study shows that a longer amount of time spent communicating the diagnosis and provision of descriptions needed by patients and their families are important. This can help clinicians understand what the patient requires while being communicated their diagnosis.","To assess the needs of patients with amyotrophic lateral sclerosis (ALS) and their families when being communicated the diagnosis. We held a nationwide webinar in September 2020, titled ""ALS Café"", and distributed a self-report questionnaire to participants. This cross-sectional study included 56 respondents (patients, n = 32; family members, n = 24). Of the 56 respondents, 47 (84%) reported being anxious when they were communicated their diagnosis. The average time allocated for communicating the diagnosis was 36.3 ± 25.6 min, and 30% of respondents believed that insufficient time was allocated. Nearly half of the respondents were communicated their diagnosis by one physician, and 57% of the respondents received their diagnosis in one session. Approximately 80% of respondents received information about ventilators when they were being communicated their diagnosis, but most patients did not want to receive this information at that time. The anxious group tended to answer that the time to communicate the diagnosis was short. Meanwhile, all respondents in the mildly anxious group were provided with one or more information about the supportive contents along with the diagnosis. Moreover, in Japan, many patients with ALS and their families desire the legalization of euthanasia, which might affect decision-making. This study shows that a longer amount of time spent communicating the diagnosis and provision of descriptions needed by patients and their families are important. This can help clinicians understand what the patient requires while being communicated their diagnosis.","null","null","2022-04","Acta Neurologica Belgica","Acta Neurologica Belgica","Vol.122","No.2","471","478","eng","true","null","scientific_journal","null","null","10.1007/s13760-021-01801-3","2240-2993","null","null","null","null","null" "Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials.","Therapeutic Devices for Motor Symptoms in Parkinson's Disease: Current Progress and a Systematic Review of Recent Randomized Controlled Trials.","Joji Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, Teruo Oda, Hiroshi Nakanishi, Yuishin Izumi, Yasushi Takagi","Joji Fujikawa, Ryoma Morigaki, Nobuaki Yamamoto, Teruo Oda, Hiroshi Nakanishi, Yuishin Izumi, Yasushi Takagi","null","Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.","Invasive and non-invasive medical devices have unique characteristics, and several RCTs have been conducted for each device. Invasive devices are more effective, while non-invasive devices are less effective and have lower hurdles and risks. It is important to understand the characteristics of each device and capitalize on these.","null","null","2022-03-29","Frontiers in Aging Neuroscience","Frontiers in Aging Neuroscience","Vol.14","null","null","null","eng","true","null","scientific_journal","null","null","10.3389/fnagi.2022.807909","1663-4365","null","null","null","null","null" "Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging","Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging","Yoshiteru Tada, Toshitaka Fujihara, Kenji Shimada, Nobuaki Yamamoto, Hiroki Yamazaki, Yuishin Izumi, Masafumi Harada, Yasuhisa Kanematsu, Yasushi Takagi","Yoshiteru Tada, Toshitaka Fujihara, Kenji Shimada, Nobuaki Yamamoto, Hiroki Yamazaki, Yuishin Izumi, Masafumi Harada, Yasuhisa Kanematsu, Yasushi Takagi","null","Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.","Arterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. Overall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. Of the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). A diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.","null","null","2022-03-07","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.436","null","1","8","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2022.120223","1878-5883","null","null","null","null","null" "Serum NfL and CHI3L1 for ALS and parkinsonian disorders in the process of diagnosis","Serum NfL and CHI3L1 for ALS and parkinsonian disorders in the process of diagnosis","Shotaro Haji, Wataru Sako, N Marukami, Yusuke Osaki, Yuishin Izumi","Shotaro Haji, Wataru Sako, N Marukami, Yusuke Osaki, Yuishin Izumi","null","Serum neurofilament light chain (NfL) and chitinase 3-like 1 (CHI3L1, also called YKL-40) concentrations are attractive candidate biomarkers for neurodegenerative disorders, which include amyotrophic lateral sclerosis (ALS) and parkinsonian disorders. We aimed to assess the diagnostic power of serum NfL and CHI3L1 concentrations with regard to the early diagnosis of ALS and Parkinson's disease (PD). We studied 157 individuals, which included 41 healthy controls, 8 patients with ALS mimics, 18 patients initially diagnosed with ALS (ID-ALS), 32 patients late-diagnosed with ALS (LD-ALS), 29 patients with PD, 12 patients with PD mimics, and 17 patients initially diagnosed with atypical parkinsonian disorders (ID-APDs) at the initial stage of diagnosis. Electrochemiluminescence was used to measure the concentrations of serum NfL and CHI3L1, the diagnostic performance of which was assessed using the area under the receiver operating curves (AUCs). The AUCs of serum NfL were 0.90 for discriminating ALS mimics from LD-ALS at the initial stage of diagnosis and 0.89 for discriminating ALS mimics from ALS (LD/ID-ALS). The AUCs of serum NfL were 0.76 for discriminating PD from PD mimics at the initial stage of diagnosis, and 0.80 for discriminating PD from APD. No significant difference existed in serum CHI3L1 concentrations between individuals with suspected ALS or parkinsonism (p = 0.14, and p = 0.44, respectively). Serum NfL had excellent and almost good diagnostic performances for patients with ALS and PD, respectively, at the initial stage of diagnosis, whereas no significant difference existed in serum CHI3L1 between any groups.","Serum neurofilament light chain (NfL) and chitinase 3-like 1 (CHI3L1, also called YKL-40) concentrations are attractive candidate biomarkers for neurodegenerative disorders, which include amyotrophic lateral sclerosis (ALS) and parkinsonian disorders. We aimed to assess the diagnostic power of serum NfL and CHI3L1 concentrations with regard to the early diagnosis of ALS and Parkinson's disease (PD). We studied 157 individuals, which included 41 healthy controls, 8 patients with ALS mimics, 18 patients initially diagnosed with ALS (ID-ALS), 32 patients late-diagnosed with ALS (LD-ALS), 29 patients with PD, 12 patients with PD mimics, and 17 patients initially diagnosed with atypical parkinsonian disorders (ID-APDs) at the initial stage of diagnosis. Electrochemiluminescence was used to measure the concentrations of serum NfL and CHI3L1, the diagnostic performance of which was assessed using the area under the receiver operating curves (AUCs). The AUCs of serum NfL were 0.90 for discriminating ALS mimics from LD-ALS at the initial stage of diagnosis and 0.89 for discriminating ALS mimics from ALS (LD/ID-ALS). The AUCs of serum NfL were 0.76 for discriminating PD from PD mimics at the initial stage of diagnosis, and 0.80 for discriminating PD from APD. No significant difference existed in serum CHI3L1 concentrations between individuals with suspected ALS or parkinsonism (p = 0.14, and p = 0.44, respectively). Serum NfL had excellent and almost good diagnostic performances for patients with ALS and PD, respectively, at the initial stage of diagnosis, whereas no significant difference existed in serum CHI3L1 between any groups.","null","null","2022-03","Journal of Neural Transmission","Journal of Neural Transmission","Vol.129","No.3","301","309","eng","true","null","scientific_journal","null","null","10.1007/s00702-022-02470-z","1435-1463","null","null","null","null","null" "The claw sign predicts first-pass effect in mechanical thrombectomy for cerebral large vessel occlusion in the anterior circulation","The claw sign predicts first-pass effect in mechanical thrombectomy for cerebral large vessel occlusion in the anterior circulation","Yuki Yamamoto, Nobuaki Yamamoto, Yasuhisa Kanematsu, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kenji Shimada, Yasushi Takagi, Yuishin Izumi","Yuki Yamamoto, Nobuaki Yamamoto, Yasuhisa Kanematsu, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Shu Sogabe, Kenji Shimada, Yasushi Takagi, Yuishin Izumi","null","Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the ""claw sign,"" was examined as candidate preoperative imaging factor for predicting the FPE. We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE. FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01-7.06; = 0.047). The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke.","Mechanical thrombectomy (MT) is an effective treatment for acute cerebral large vessel occlusion (LVO). Complete recanalization of vessels in a single procedure is defined as the first-pass effect (FPE) and is associated with good prognosis. In this study, angiographic clot protruding sign termed the ""claw sign,"" was examined as candidate preoperative imaging factor for predicting the FPE. We retrospectively analyzed data from 91 consecutive patients treated for acute LVO in the anterior circulation by MT between January 2014 and December 2019. The claw sign was defined as a thrombus that protruded proximally by more than half of the diameter of the parent artery. Radiological findings such as claw sign, clinical and etiological features, and outcomes were compared between groups with and without successful FPE. Multivariate analysis was conducted to evaluate perioperative factors associated with FPE. FPE was achieved in 26 of 91 (28.6%) patients and the claw sign was observed in 34 of 91 (37.4%) patients. The claw sign was significantly more frequent in the successful FPE group than in the failed FPE group (53.8% vs. 30.8%; = 0.040). After the multivariate analysis, the claw sign was the only pretreatment parameter that could predict FPE (odds ratio, 2.67; 95% confidence interval, 1.01-7.06; = 0.047). The claw sign is an angiographic imaging factor that might predict FPE after MT for anterior circulation acute ischemic stroke.","null","null","2022-02-25","Surgical Neurology International","Surgical Neurology International","Vol.13","No.72","1","7","eng","true","null","scientific_journal","null","null","10.25259/SNI_1160_2021","2229-5097","null","null","null","null","null" "血管炎性ニューロパチー様の臨床像で発症した抗Hu抗体陽性脳脊髄炎の1例","血管炎性ニューロパチー様の臨床像で発症した抗Hu抗体陽性脳脊髄炎の1例","大崎 裕亮, 島 かさ音, 山本 伸昭, 山﨑 博輝, 佐藤 健太, 和泉 唯信","Yusuke Osaki, 島 かさ音, Nobuaki Yamamoto, Hiroki Yamazaki, Kenta Sato, Yuishin Izumi","null","null","null","null","null","2022","Peripheral Nerve","Peripheral Nerve","Vol.33","No.1","136","143","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null" "Clinical safety and tolerability of A2NTX, a novel low-molecular-weight neurotoxin derived from botulinum neurotoxin subtype A2, in comparison with subtype A1 toxins","Clinical safety and tolerability of A2NTX, a novel low-molecular-weight neurotoxin derived from botulinum neurotoxin subtype A2, in comparison with subtype A1 toxins","T Takeuchi, T Okuno, A Miyashiro, T Kohda, Ryosuke Miyamoto, Yuishin Izumi, S Kozaki, Ryuji Kaji","T Takeuchi, T Okuno, A Miyashiro, T Kohda, Ryosuke Miyamoto, Yuishin Izumi, S Kozaki, Ryuji Kaji","null","All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (LL type A1 toxin, or onabotulinumtoxinA) and a low-molecular-weight (150 kD) A1 neurotoxin (A1NTX). Those who had been using A1LL ( = 90; 50-360 mouse LD50 units) or A1NTX ( = 30; 50-580 units) were switched to A2NTX ( = 120; 25-600 units) from 2010 to 2018 (number of sessions ~27, cumulative doses ~11,640 units per patient). The adverse events for A2NTX included weakness ( = 1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), and spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness ( = 2, A1NTX), dysphagia (8), ptosis (6), local weakness (7), and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had clinical safety up to the dose of 500 units and was well tolerated compared to A1 toxins.","All the botulinum type A neurotoxins available for clinical use are of the A1 subtype. We developed a subtype A2 low-molecular-weight (150 kD (kilo Dalton)) neurotoxin (A2NTX) with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed that its efficacy is superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (LL type A1 toxin, or onabotulinumtoxinA) and a low-molecular-weight (150 kD) A1 neurotoxin (A1NTX). Those who had been using A1LL ( = 90; 50-360 mouse LD50 units) or A1NTX ( = 30; 50-580 units) were switched to A2NTX ( = 120; 25-600 units) from 2010 to 2018 (number of sessions ~27, cumulative doses ~11,640 units per patient). The adverse events for A2NTX included weakness ( = 1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), and spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness ( = 2, A1NTX), dysphagia (8), ptosis (6), local weakness (7), and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had clinical safety up to the dose of 500 units and was well tolerated compared to A1 toxins.","null","null","2021-11-22","Toxins","Toxins","Vol.13","No.11","824","824","eng","true","null","scientific_journal","null","null","10.3390/toxins13110824","2072-6651","null","null","null","null","null" "MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis","MR spectroscopy and imaging-derived measurements in the supplementary motor area for biomarkers of amyotrophic lateral sclerosis","Wataru Sako, Yuishin Izumi, Takashi Abe, Shotaro Haji, Nagahisa Murakami, Yusuke Osaki, Yuki Matsumoto, Masafumi Harada, Ryuji Kaji","Wataru Sako, Yuishin Izumi, Takashi Abe, Shotaro Haji, Nagahisa Murakami, Yusuke Osaki, Yuki Matsumoto, Masafumi Harada, Ryuji Kaji","null","null","null","null","null","2021-10","Neurological Sciences","Neurological Sciences","Vol.42","No.10","4257","4263","eng","true","null","scientific_journal","null","null","10.1007/s10072-021-05107-3","1590-3478","null","null","null","null","null" """Burnt-out"" progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia","""Burnt-out"" progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia","T Fukumoto, Y Sakashita, F Katada, R Takeuchi, Ryosuke Miyamoto, Yuishin Izumi, S Sato, H Shibayama, K Takahashi, T Suzuki, K Nakamichi, S Murayama, T Fukutake","T Fukumoto, Y Sakashita, F Katada, R Takeuchi, Ryosuke Miyamoto, Yuishin Izumi, S Sato, H Shibayama, K Takahashi, T Suzuki, K Nakamichi, S Murayama, T Fukutake","null","Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by John Cunningham virus (JCV) infection; however, a growing number of PML patients now survive longer and achieve remission, largely due to the advent of combination antiretroviral therapy. Several reports have suggested that the pathology in such patients presents only chronic demyelination without characteristic cellular changes, being referred to as ""burnt-out"" PML. On the other hand, our knowledge of ""burnt-out"" PML is still substantially limited, especially in patients with non-human immunodeficiency virus infection. Here, we report a case of PML associated with idiopathic CD4 lymphocytopenia (ICL) who presented with spontaneous remission and survived for 11 years after onset. Notably, postmortem examination revealed surprisingly broad ""burnt-out"" lesions lacking the classic histopathological findings. However, pathogenic JCV-specific DNA sequences was still present in the autopsied brain tissue. This case suggests that complete remission can be achieved with a persistent presence of JCV-specific pathogenic sequences, even after a catastrophic infection. Considering that there have been a few reported cases of PML with ICL with long survival, the long-term survival of our case may share a favorable immunological response that is unique to a subgroup of ICL.","Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by John Cunningham virus (JCV) infection; however, a growing number of PML patients now survive longer and achieve remission, largely due to the advent of combination antiretroviral therapy. Several reports have suggested that the pathology in such patients presents only chronic demyelination without characteristic cellular changes, being referred to as ""burnt-out"" PML. On the other hand, our knowledge of ""burnt-out"" PML is still substantially limited, especially in patients with non-human immunodeficiency virus infection. Here, we report a case of PML associated with idiopathic CD4 lymphocytopenia (ICL) who presented with spontaneous remission and survived for 11 years after onset. Notably, postmortem examination revealed surprisingly broad ""burnt-out"" lesions lacking the classic histopathological findings. However, pathogenic JCV-specific DNA sequences was still present in the autopsied brain tissue. This case suggests that complete remission can be achieved with a persistent presence of JCV-specific pathogenic sequences, even after a catastrophic infection. Considering that there have been a few reported cases of PML with ICL with long survival, the long-term survival of our case may share a favorable immunological response that is unique to a subgroup of ICL.","null","null","2021-09-30","Neuropathology","Neuropathology","Vol.41","No.6","484","488","eng","true","null","scientific_journal","null","null","10.1111/neup.12773","1440-1789","null","null","null","null","null" "Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.","Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease.","Yohei Yamamoto, Naoko Matsui, Akiyuki Uzawa, Yukiko Ozawa, Tetsuya Kanai, Fumiko Oda, Hiroyuki Kondo, Izumi Ohigashi, Hiromitsu Takizawa, Kazuya Kondo, Mikio Sugano, Takashi Kitaichi, Hiroki Hata, Ryuji Kaji, Satoshi Kuwabara, Takashi Yamamura, Yuishin Izumi","Yohei Yamamoto, Naoko Matsui, Akiyuki Uzawa, Yukiko Ozawa, Tetsuya Kanai, Fumiko Oda, Hiroyuki Kondo, Izumi Ohigashi, Hiromitsu Takizawa, Kazuya Kondo, Mikio Sugano, Takashi Kitaichi, Hiroki Hata, Ryuji Kaji, Satoshi Kuwabara, Takashi Yamamura, Yuishin Izumi","null","Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.","Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.","null","null","2021-09-24","Neurology® Neuroimmunology & Neuroinflammation","Neurology® Neuroimmunology & Neuroinflammation","Vol.8","No.6","e1087","e1087","eng","true","null","scientific_journal","null","null","10.1212/NXI.0000000000001087","2332-7812","null","null","null","null","null" "Novel monoallelic variant in ERLIN2 causes spastic paraplegia converted to amyotrophic lateral sclerosis","Novel monoallelic variant in ERLIN2 causes spastic paraplegia converted to amyotrophic lateral sclerosis","K Kume, M Kamada, Yoshimitsu Shimatani, T Takata, Yuishin Izumi, H Kawakami","K Kume, M Kamada, Yoshimitsu Shimatani, T Takata, Yuishin Izumi, H Kawakami","null","null","null","null","null","2021-09-14","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.430","null","119984","119984","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2021.119984","1878-5883","null","null","null","null","null" "Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation","Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation","Masaaki Nishi, Ryosuke Miyamoto, Kasane Shima, Hirokazu Miki, Hideo Terasawa, Chie Takasu, Kouzou Yoshikawa, Takuro Oyama, Katsuya Tanaka, Yuishin Izumi, Mitsuo Shimada","Masaaki Nishi, Ryosuke Miyamoto, Kasane Shima, Hirokazu Miki, Hideo Terasawa, Chie Takasu, Kouzou Yoshikawa, Takuro Oyama, Katsuya Tanaka, Yuishin Izumi, Mitsuo Shimada","null","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Although affected patients may develop cancers, major surgical intervention has been hampered by its questionable overall benefit due to limited prognosis and risk of postoperative respiratory collapse. A recent study, however, showed that tracheostomy invasive ventilation (TIV) prolonged median survival to 11.3 years; thus, patients with ALS receiving TIV might benefit from major surgery. A 66-year-old man with ALS, who had received TIV and enteral tube feeding for 8 years, presented with bloody stool. The patient also had type 2 diabetes mellitus, stage 4 chronic kidney disease, abdominal aortic aneurysm, and anti-phospholipid syndrome, as well as multiple episodes of pneumonia and catheter-related urinary tract infection treated by antibiotics. Medical examination and esophagogastroduodenoscopy revealed a type 3 tumor in the middle part of the stomach. The patient's preoperative diagnosis was gastric cancer (GC), MU, type3, Less-Post, T3(SS), N1, H0, P0, M0, cStage III. The estimated mortality rate was 30.5%, according to the Japanese National Clinical Database. The patient and his family were fully informed of the risk of surgery; the patient clearly requested curative surgery by eye movement. Thus, robot-assisted total gastrectomy (RATG) was performed. The tissues were extremely fragile and hemorrhagic. The surgical time was 7 h 0 min; intraoperative blood loss was 324 ml. Pathological examination revealed GC, MU, type3, T4a(SE), N2, H0, CY0, P0, M0 fStage IIIB. The postoperative course was uneventful. He has remained in stable condition for 3 months. Our findings suggest that patients with ALS who achieve longer survival with TIV can undergo major cancer surgery, including robot-assisted surgery, which may facilitate a better mid-long-term prognosis. The online version contains supplementary material available at 10.1007/s13691-021-00499-7.","Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Although affected patients may develop cancers, major surgical intervention has been hampered by its questionable overall benefit due to limited prognosis and risk of postoperative respiratory collapse. A recent study, however, showed that tracheostomy invasive ventilation (TIV) prolonged median survival to 11.3 years; thus, patients with ALS receiving TIV might benefit from major surgery. A 66-year-old man with ALS, who had received TIV and enteral tube feeding for 8 years, presented with bloody stool. The patient also had type 2 diabetes mellitus, stage 4 chronic kidney disease, abdominal aortic aneurysm, and anti-phospholipid syndrome, as well as multiple episodes of pneumonia and catheter-related urinary tract infection treated by antibiotics. Medical examination and esophagogastroduodenoscopy revealed a type 3 tumor in the middle part of the stomach. The patient's preoperative diagnosis was gastric cancer (GC), MU, type3, Less-Post, T3(SS), N1, H0, P0, M0, cStage III. The estimated mortality rate was 30.5%, according to the Japanese National Clinical Database. The patient and his family were fully informed of the risk of surgery; the patient clearly requested curative surgery by eye movement. Thus, robot-assisted total gastrectomy (RATG) was performed. The tissues were extremely fragile and hemorrhagic. The surgical time was 7 h 0 min; intraoperative blood loss was 324 ml. Pathological examination revealed GC, MU, type3, T4a(SE), N2, H0, CY0, P0, M0 fStage IIIB. The postoperative course was uneventful. He has remained in stable condition for 3 months. Our findings suggest that patients with ALS who achieve longer survival with TIV can undergo major cancer surgery, including robot-assisted surgery, which may facilitate a better mid-long-term prognosis. The online version contains supplementary material available at 10.1007/s13691-021-00499-7.","null","null","2021-07-12","International Cancer Conference Journal","International Cancer Conference Journal","Vol.10","No.4","318","323","eng","true","null","scientific_journal","null","null","10.1007/s13691-021-00499-7","2192-3183","null","null","null","null","null" "Percutaneous Transluminal Angioplasty and Stenting Using an Aspiration Catheter","Percutaneous Transluminal Angioplasty and Stenting Using an Aspiration Catheter","Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yuishin Izumi, Yasushi Takagi","Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yuishin Izumi, Yasushi Takagi","null","
Objective: During percutaneous transluminal angioplasty (PTA) for the vertebral artery, occlusion of the subclavian artery using a balloon guiding catheter may be useful to prevent embolism of clots and/or debris distal to an atherosclerotic lesion. However, when placing a balloon guiding catheter at the intended vessels is difficult, it may be useful to use an aspiration catheter (AC) for mechanical thrombectomy as an intermediate catheter to suction way clots and/or debris. We report two cases in which PTA was performed for an atherosclerotic lesion at the intracranial vertebral artery using an AC, which ended without complications.
Case Presentations: Case 1: A 74-year-old man presented with dysarthria and was admitted to our hospital. MRI revealed severe left vertebral artery stenosis and diffuse cerebral infarct areas at the territory of the posterior circulation. The patient had an abdominal aortic aneurysm and abnormally shaped left tortuous subclavian artery. Therefore, we performed PTA and stenting via the left brachial artery. We guided a 6-Fr long sheath to the left subclavian artery, and a 6-Fr AC for thrombectomy was guided through the long sheath to the V4 portion of the left vertebral artery. Thereafter, PTA was carried out under manual aspiration from the AC. As restenosis at the atherosclerotic lesion occurred after PTA, we performed stenting using a coronary stent system for this lesion under manual aspiration from the AC. No new infarct areas were observed on post-procedural MRI. Case 2: A 74-year-old woman presented with dysarthria and was admitted to our hospital. MRI demonstrated basilar artery occlusion and diffuse cerebral infarct areas at the territory of the posterior circulation. As her symptom worsened after admission, we performed urgent mechanical thrombectomy. We first performed thrombectomy using a stent retriever and then performed PTA and stenting (PTAS) for residual basilar artery stenosis via the AC under manual aspiration.
Conclusion: When it is difficult to place a guiding catheter at the intended vessels during PTA, an AC may be useful to prevent distal embolization.
","Objective: During percutaneous transluminal angioplasty (PTA) for the vertebral artery, occlusion of the subclavian artery using a balloon guiding catheter may be useful to prevent embolism of clots and/or debris distal to an atherosclerotic lesion. However, when placing a balloon guiding catheter at the intended vessels is difficult, it may be useful to use an aspiration catheter (AC) for mechanical thrombectomy as an intermediate catheter to suction way clots and/or debris. We report two cases in which PTA was performed for an atherosclerotic lesion at the intracranial vertebral artery using an AC, which ended without complications.
Case Presentations: Case 1: A 74-year-old man presented with dysarthria and was admitted to our hospital. MRI revealed severe left vertebral artery stenosis and diffuse cerebral infarct areas at the territory of the posterior circulation. The patient had an abdominal aortic aneurysm and abnormally shaped left tortuous subclavian artery. Therefore, we performed PTA and stenting via the left brachial artery. We guided a 6-Fr long sheath to the left subclavian artery, and a 6-Fr AC for thrombectomy was guided through the long sheath to the V4 portion of the left vertebral artery. Thereafter, PTA was carried out under manual aspiration from the AC. As restenosis at the atherosclerotic lesion occurred after PTA, we performed stenting using a coronary stent system for this lesion under manual aspiration from the AC. No new infarct areas were observed on post-procedural MRI. Case 2: A 74-year-old woman presented with dysarthria and was admitted to our hospital. MRI demonstrated basilar artery occlusion and diffuse cerebral infarct areas at the territory of the posterior circulation. As her symptom worsened after admission, we performed urgent mechanical thrombectomy. We first performed thrombectomy using a stent retriever and then performed PTA and stenting (PTAS) for residual basilar artery stenosis via the AC under manual aspiration.
Conclusion: When it is difficult to place a guiding catheter at the intended vessels during PTA, an AC may be useful to prevent distal embolization.
","null","null","2021-07","Journal of Neuroendovascular Therapy","Journal of Neuroendovascular Therapy","Vol.16","No.5","277","282","eng","true","null","scientific_journal","null","null","10.5797/jnet.cr.2021-0030","1882-4072","null","https://www.jstage.jst.go.jp/article/jnet/advpub/0/advpub_cr.2021-0030/_pdf","null","null","null" "Peripheral nerve dysfunction in a patient with thyrotoxic periodic paralysis: Evidence from an axonal prolonged exercise test","Peripheral nerve dysfunction in a patient with thyrotoxic periodic paralysis: Evidence from an axonal prolonged exercise test","Yusuke Osaki, Hiroyuki Nodera, Tatsuya Fukumoto, Ryuji Kaji, Yuishin Izumi","Yusuke Osaki, Hiroyuki Nodera, Tatsuya Fukumoto, Ryuji Kaji, Yuishin Izumi","null","null","null","null","null","2021-07","Clinical Neurophysiology","Clinical Neurophysiology","Vol.132","No.7","1496","1498","eng","true","null","scientific_journal","null","null","10.1016/j.clinph.2021.04.006","1872-8952","null","null","null","null","null" "Gait apraxia as a presenting sign of Gerstmann-Sträussler-Scheinker disease","Gait apraxia as a presenting sign of Gerstmann-Sträussler-Scheinker disease","T Fukumoto, Ryosuke Miyamoto, Koji Fujita, Masafumi Harada, Yuishin Izumi","T Fukumoto, Ryosuke Miyamoto, Koji Fujita, Masafumi Harada, Yuishin Izumi","null","null","null","null","null","2021-07","Neurology and Clinical Neuroscience","Neurology and Clinical Neuroscience","Vol.9","No.4","339","341","eng","true","null","scientific_journal","null","null","10.1111/ncn3.12511","2049-4173","null","null","null","null","null" "Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sjögren's syndrome","Detection of nerve enlargement with ultrasound and correlation with skin biopsy findings in painful sensory neuropathy associated with Sjögren's syndrome","T Yoshida, Hiroyuki Nodera, Y Kumon, S Osanai, Yuishin Izumi, H Mizukami","T Yoshida, Hiroyuki Nodera, Y Kumon, S Osanai, Yuishin Izumi, H Mizukami","null","We evaluated usefulness of peripheral nerve ultrasound (US) in detecting abnormality in painful sensory neuropathy (PSN) associated with primary Sjögren's syndrome (pSS), and associations among various clinical factors, US findings, and intraepidermal nerve fiber density (IENFD). We conducted a retrospective, single-center, observational study of patients with pSS-PSN. US image was obtained to measure cross sectional area (CSA) of peripheral nerves and compared with matched pSS control. We included 11 patients with pSS-PSN (10 women; age 70.5 ± 5.66) and 17 pSS controls (15 women; age 62.5 ± 16.7). Sural nerve CSA were significantly increased in pSS-PSN group (3.48 ± 1.0 mm vs 2.05 ± 0.65 mm, = .001). US of sural nerve showed the area under the ROC curve of 0.872 (95% CI, 0.732 - 1). Sural nerve CSA and IENFD of lower leg showed positive correlation. Compared with pSS-PSN patients with abnormal IENFD, those with normal IENFD showed significantly larger sural nerve CSA, and trends toward less systemic disease activity and small fiber impairment with sparing of large fibers. US was useful in discriminating pSS patients with PSN from those without. Additionally, US may disclose distinct subsets of pSS-PSN with different clinical findings and IENFD.","We evaluated usefulness of peripheral nerve ultrasound (US) in detecting abnormality in painful sensory neuropathy (PSN) associated with primary Sjögren's syndrome (pSS), and associations among various clinical factors, US findings, and intraepidermal nerve fiber density (IENFD). We conducted a retrospective, single-center, observational study of patients with pSS-PSN. US image was obtained to measure cross sectional area (CSA) of peripheral nerves and compared with matched pSS control. We included 11 patients with pSS-PSN (10 women; age 70.5 ± 5.66) and 17 pSS controls (15 women; age 62.5 ± 16.7). Sural nerve CSA were significantly increased in pSS-PSN group (3.48 ± 1.0 mm vs 2.05 ± 0.65 mm, = .001). US of sural nerve showed the area under the ROC curve of 0.872 (95% CI, 0.732 - 1). Sural nerve CSA and IENFD of lower leg showed positive correlation. Compared with pSS-PSN patients with abnormal IENFD, those with normal IENFD showed significantly larger sural nerve CSA, and trends toward less systemic disease activity and small fiber impairment with sparing of large fibers. US was useful in discriminating pSS patients with PSN from those without. Additionally, US may disclose distinct subsets of pSS-PSN with different clinical findings and IENFD.","null","null","2021-07","Modern Rheumatology","Modern Rheumatology","Vol.31","No.4","849","855","eng","true","null","scientific_journal","null","null","10.1080/14397595.2020.1830484","1439-7609","null","null","null","null","null" "Repurposing bromocriptine for Aβ metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations.","Repurposing bromocriptine for Aβ metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations.","Takayuki Kondo, Haruhiko Banno, Taro Okunomiya, Yoko Amino, Kayoko Endo, Akiyoshi Nakakura, Ryuji Uozumi, Akemi Kinoshita, Harue Tada, Satoshi Morita, Hidehiro Ishikawa, Akihiro Shindo, Ken Yasuda, Yosuke Taruno, Takakuni Maki, Takashi Suehiro, Kohji Mori, Manabu Ikeda, Koji Fujita, Yuishin Izumi, Kazutomi Kanemaru, Kenji Ishii, Kazue Shigenobu, Yumiko Kutoku, Yoshihide Sunada, Shinobu Kawakatsu, Shunji Shiota, Toshifumi Watanabe, Osamu Uchikawa, Ryosuke Takahashi, Hidekazu Tomimoto, Haruhisa Inoue","Takayuki Kondo, Haruhiko Banno, Taro Okunomiya, Yoko Amino, Kayoko Endo, Akiyoshi Nakakura, Ryuji Uozumi, Akemi Kinoshita, Harue Tada, Satoshi Morita, Hidehiro Ishikawa, Akihiro Shindo, Ken Yasuda, Yosuke Taruno, Takakuni Maki, Takashi Suehiro, Kohji Mori, Manabu Ikeda, Koji Fujita, Yuishin Izumi, Kazutomi Kanemaru, Kenji Ishii, Kazue Shigenobu, Yumiko Kutoku, Yoshihide Sunada, Shinobu Kawakatsu, Shunji Shiota, Toshifumi Watanabe, Osamu Uchikawa, Ryosuke Takahashi, Hidekazu Tomimoto, Haruhisa Inoue","null","This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted.","jRCT2041200008, NCT04413344.","null","null","2021-06-30","BMJ Open","BMJ Open","Vol.11","No.6","e051343","e051343","eng","true","null","scientific_journal","null","null","10.1136/bmjopen-2021-051343","2044-6055","null","null","null","null","null" "Repurposing bromocriptine for Aβ metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations","Repurposing bromocriptine for Aβ metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations","T Kondo, H Banno, T Okunomiya, Y Amino, K Endo, A Nakakura, R Uozumi, A Kinoshita, H Tada, S Morita, H Ishikawa, A Shindo, K Yasuda, Y Taruno, T Maki, T Suehiro, K Mori, M Ikeda, Koji Fujita, Yuishin Izumi, K Kanemaru, K Ishii, K Shigenobu, Y Kutoku, Y Sunada, S Kawakatsu, S Shiota, T Watanabe, O Uchikawa, R Takahashi, H Tomimoto, H Inoue","T Kondo, H Banno, T Okunomiya, Y Amino, K Endo, A Nakakura, R Uozumi, A Kinoshita, H Tada, S Morita, H Ishikawa, A Shindo, K Yasuda, Y Taruno, T Maki, T Suehiro, K Mori, M Ikeda, Koji Fujita, Yuishin Izumi, K Kanemaru, K Ishii, K Shigenobu, Y Kutoku, Y Sunada, S Kawakatsu, S Shiota, T Watanabe, O Uchikawa, R Takahashi, H Tomimoto, H Inoue","null","null","null","null","null","2021-06-30","BMJ Open","BMJ Open","Vol.11","No.6","e051343","e051343","eng","true","null","scientific_journal","null","null","10.1136/bmjopen-2021-051343","2044-6055","null","null","null","null","null" "The cerebellum is a common key for visuospatial execution and attention in Parkinson's disease","The cerebellum is a common key for visuospatial execution and attention in Parkinson's disease","Wataru Sako, T Abe, Y Matsumoto, K Nakamura, Shotaro Haji, Yusuke Osaki, Masafumi Harada, Yuishin Izumi","Wataru Sako, T Abe, Y Matsumoto, K Nakamura, Shotaro Haji, Yusuke Osaki, Masafumi Harada, Yuishin Izumi","null","Cognitive decline affects the clinical course in patients with Parkinson's disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network ( = 0.54, < 0.001), naming-domain-related network ( = 0.39, < 0.001), attention-domain-related network ( = 0.86, < 0.001), language-domain-related network ( = 0.64, < 0.001), abstraction-related network ( = 0.10, < 0.05), and orientation-domain-related network ( = 0.64, < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.","Cognitive decline affects the clinical course in patients with Parkinson's disease (PD) and contributes to a poor prognosis. However, little is known about the underlying network-level abnormalities associated with each cognitive domain. We aimed to identify the networks related to each cognitive domain in PD using resting-state functional magnetic resonance imaging (MRI). Forty patients with PD and 15 normal controls were enrolled. All subjects underwent MRI and the Mini-Mental State Examination. Furthermore, the cognitive function of patients with PD was assessed using the Montreal Cognitive Assessment (MoCA). We used independent component analysis of the resting-state functional MRI for functional segmentation, followed by reconstruction to identify each domain-related network, to predict scores in PD using multiple regression models. Six networks were identified, as follows: the visuospatial-executive-domain-related network ( = 0.54, < 0.001), naming-domain-related network ( = 0.39, < 0.001), attention-domain-related network ( = 0.86, < 0.001), language-domain-related network ( = 0.64, < 0.001), abstraction-related network ( = 0.10, < 0.05), and orientation-domain-related network ( = 0.64, < 0.001). Cerebellar lobule VII was involved in the visuospatial-executive-domain-related and attention-domain-related networks. These two domains are involved in the first three listed nonamnestic cognitive impairment in the diagnostic criteria for PD with dementia (PDD). Furthermore, Brodmann area 10 contributed most frequently to each domain-related network. Collectively, these findings suggest that cerebellar lobule VII may play a key role in cognitive impairment in nonamnestic types of PDD.","null","null","2021-06-06","Diagnostics","Diagnostics","Vol.11","No.6","1042","1042","eng","true","null","scientific_journal","null","null","10.3390/diagnostics11061042","2075-4418","null","http://repo.lib.tokushima-u.ac.jp/116520","null","null","null" "Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia","Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia","Hiroshi Koyama, Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Taku Matsuda, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Satoshi Goto, Yasushi Takagi","Hiroshi Koyama, Hideo Mure, Ryoma Morigaki, Ryosuke Miyamoto, Kazuhisa Miyake, Taku Matsuda, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Satoshi Goto, Yasushi Takagi","null","Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.","Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.","null","null","2021-05-24","Life","Life","Vol.11","No.6","477","477","eng","true","null","scientific_journal","null","null","10.3390/life11060477","2075-1729","null","null","null","null","null" "Stiff-Person Syndrome","Stiff-Person Syndrome","松井 尚子, 田中 惠子, 和泉 唯信","Naoko Matsui, 田中 惠子, Yuishin Izumi","null","null","null","null","null","2021-05","脳と神経 - 神経研究の進歩","Brain and Nerve = Shinkei kenkyū no shinpo","Vol.73","No.5","640","646","jpn","true","null","scientific_journal","null","null","null","1881-6096","null","http://id.ndl.go.jp/bib/031510247","null","null","null" "A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma","A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma","Kohei Muto, Ryosuke Miyamoto, Yuka Terasawa, Yoshimitsu Shimatani, Keijiro Hara, Takumi Kakimoto, Tatsuya Fukumoto, Yusuke Osaki, Koji Fujita, Masafumi Harada, Hisanori Uehara, Yasushi Takagi, Yuishin Izumi","Kohei Muto, Ryosuke Miyamoto, Yuka Terasawa, Yoshimitsu Shimatani, Keijiro Hara, Takumi Kakimoto, Tatsuya Fukumoto, Yusuke Osaki, Koji Fujita, Masafumi Harada, Hisanori Uehara, Yasushi Takagi, Yuishin Izumi","null","null","null","null","null","2021-05","Human Genome Variation","Human Genome Variation","Vol.8","No.1","18","18","eng","true","null","scientific_journal","null","null","10.1038/s41439-021-00150-0","2054-345X","null","null","null","null","null" "An autopsy report of a familial amyotrophic lateral sclerosis case carrying VCP Arg487His mutation with a unique TDP-43 proteinopathy","An autopsy report of a familial amyotrophic lateral sclerosis case carrying VCP Arg487His mutation with a unique TDP-43 proteinopathy","Tomoyasu Matsubara, Yuishin Izumi, Masaya Oda, Masatoshi Takahashi, Hirofumi Maruyama, Ryosuke Miyamoto, Chigusa Watanabe, Yoshiro Tachiyama, Hiroyuki Morino, Hideshi Kawakami, Yuko Saito, Shigeo Murayama","Tomoyasu Matsubara, Yuishin Izumi, Masaya Oda, Masatoshi Takahashi, Hirofumi Maruyama, Ryosuke Miyamoto, Chigusa Watanabe, Yoshiro Tachiyama, Hiroyuki Morino, Hideshi Kawakami, Yuko Saito, Shigeo Murayama","null","We here report an autopsy case of familial amyotrophic lateral sclerosis (ALS) with p.Arg487His mutation in the valosin-containing protein (VCP) gene (VCP), in which upper motor neurons (UMNs) were predominantly involved. Moreover, our patient developed symptoms of frontotemporal dementia later in life and pathologically exhibited numerous phosphorylated transactivation response DNA-binding protein of 43 kDa (p-TDP-43)-positive neuronal cytoplasmic inclusions and short dystrophic neurites with a few lentiform neuronal intranuclear inclusions, sharing the features of frontotemporal lobar degeneration with TDP-43 pathology type A pattern. A review of previous reports of ALS with VCP mutations suggests that our case is unique in terms of its UMN-predominant lesion pattern and distribution of p-TDP-43 pathology. Thus, this case report effectively expands the clinical and pathological phenotype of ALS in patients with a VCP mutation.","We here report an autopsy case of familial amyotrophic lateral sclerosis (ALS) with p.Arg487His mutation in the valosin-containing protein (VCP) gene (VCP), in which upper motor neurons (UMNs) were predominantly involved. Moreover, our patient developed symptoms of frontotemporal dementia later in life and pathologically exhibited numerous phosphorylated transactivation response DNA-binding protein of 43 kDa (p-TDP-43)-positive neuronal cytoplasmic inclusions and short dystrophic neurites with a few lentiform neuronal intranuclear inclusions, sharing the features of frontotemporal lobar degeneration with TDP-43 pathology type A pattern. A review of previous reports of ALS with VCP mutations suggests that our case is unique in terms of its UMN-predominant lesion pattern and distribution of p-TDP-43 pathology. Thus, this case report effectively expands the clinical and pathological phenotype of ALS in patients with a VCP mutation.","null","null","2021-04","Neuropathology","Neuropathology","Vol.41","No.2","118","126","eng","true","null","scientific_journal","null","null","10.1111/neup.12710","1440-1789","null","null","null","null","null" "The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis","The value of serum uric acid as a prognostic biomarker in amyotrophic lateral sclerosis: Evidence from a meta-analysis","Shotaro Haji, Wataru Sako, Nagahisa Murakami, Yusuke Osaki, Takahiro Furukawa, Yuishin Izumi, Ryuji Kaji","Shotaro Haji, Wataru Sako, Nagahisa Murakami, Yusuke Osaki, Takahiro Furukawa, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2021-04","Clinical Neurology and Neurosurgery","Clinical Neurology and Neurosurgery","Vol.203","null","106566","106566","eng","true","null","scientific_journal","null","null","10.1016/j.clineuro.2021.106566","0303-8467","null","null","null","null","null" "Magnetic resonance tractography exhibiting retrograde degeneration of the corticospinal tract in a patient with a unilateral spinal cord tumor","Magnetic resonance tractography exhibiting retrograde degeneration of the corticospinal tract in a patient with a unilateral spinal cord tumor","Yusuke Osaki, Wataru Sako, Masafumi Harada, Yuishin Izumi","Yusuke Osaki, Wataru Sako, Masafumi Harada, Yuishin Izumi","null","null","null","null","null","2021-04","Brain and Behavior","Brain and Behavior","Vol.11","No.4","e02020","e02020","eng","true","null","scientific_journal","null","null","10.1002/brb3.2020","2162-3279","null","null","null","null","null" "Analysis of genetic risk factors in Japanese patients with Parkinson's disease","Analysis of genetic risk factors in Japanese patients with Parkinson's disease","Y Kanaya, K Kume, Hiroyuki Morino, R Ohsawa, T Kurashige, M Kamada, T Torii, Yuishin Izumi, H Maruyama, H Kawakami","Y Kanaya, K Kume, Hiroyuki Morino, R Ohsawa, T Kurashige, M Kamada, T Torii, Yuishin Izumi, H Maruyama, H Kawakami","null","Parkinson's disease (PD) is caused by a combination of genetic and environmental factors. Notably, genetic risk factors vary according to ethnicity and geographical regions, and few studies have analyzed the frequency of PD causative genes in Japanese patients. Therefore, we performed genetic analyses of Japanese patients with PD. We recruited 221 participants, including 26 patients with familial PD. Genetic risk factors were evaluated by target sequencing and gene dosage analysis. We detected the genetic risk factors in 58 cases (26.2%) and classified patients into three groups to clarify the differences in genetic risk factors by age at onset (AAO). The early-onset group (AAO < 50 years) included 18 cases (44.7%), who tended to have a larger number of genetic risk factors than the later-onset groups. Regarding the AAO for each causative gene, patients with PRKN variants were significantly younger at onset than those bearing LRRK2 variants. LRRK2 variants showed similar frequency in each AAO group. Of note, we identified two novel variants. Patients with early-onset PD have more genetic risk factors than patients with late-onset PD. In Japanese patients with PD, PRKN, and LRRK2 were the major PD-related genes. Particularly, LRRK2 was a common genetic factor in all age groups because of the presence of the Asian-specific variant such as LRRK2 p.G2385R. Accumulation of genetic and clinical data can contribute to the development of treatments for PD.","Parkinson's disease (PD) is caused by a combination of genetic and environmental factors. Notably, genetic risk factors vary according to ethnicity and geographical regions, and few studies have analyzed the frequency of PD causative genes in Japanese patients. Therefore, we performed genetic analyses of Japanese patients with PD. We recruited 221 participants, including 26 patients with familial PD. Genetic risk factors were evaluated by target sequencing and gene dosage analysis. We detected the genetic risk factors in 58 cases (26.2%) and classified patients into three groups to clarify the differences in genetic risk factors by age at onset (AAO). The early-onset group (AAO < 50 years) included 18 cases (44.7%), who tended to have a larger number of genetic risk factors than the later-onset groups. Regarding the AAO for each causative gene, patients with PRKN variants were significantly younger at onset than those bearing LRRK2 variants. LRRK2 variants showed similar frequency in each AAO group. Of note, we identified two novel variants. Patients with early-onset PD have more genetic risk factors than patients with late-onset PD. In Japanese patients with PD, PRKN, and LRRK2 were the major PD-related genes. Particularly, LRRK2 was a common genetic factor in all age groups because of the presence of the Asian-specific variant such as LRRK2 p.G2385R. Accumulation of genetic and clinical data can contribute to the development of treatments for PD.","null","null","2021-03-19","Journal of Human Genetics","Journal of Human Genetics","Vol.66","No.10","957","964","eng","true","null","scientific_journal","null","null","10.1038/s10038-021-00910-4","1435-232X","null","null","null","null","null" "Diagnostic usefulness of denervation edema in the multifidus muscles using 3-Tesla magnetic resonance imaging in cervical radiculopathy","Diagnostic usefulness of denervation edema in the multifidus muscles using 3-Tesla magnetic resonance imaging in cervical radiculopathy","Takeshi Yoshida, S Suwazono, T Sueyoshi, Yuishin Izumi, Hiroyuki Nodera","Takeshi Yoshida, S Suwazono, T Sueyoshi, Yuishin Izumi, Hiroyuki Nodera","null","Diagnosing cervical radiculopathy (CR) can be difficult because of symptomatic overlap with peripheral neuropathies. In this retrospective observational study, we aimed to determine whether short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) sequences are useful for detecting signs of denervation in the multifidus muscles in patients with CR. We analyzed the data of 18 patients with CR who developed arm weakness within 1 year. We also included 10 patients with sensorimotor symptoms involving the upper extremities who did not have intervertebral foraminal stenosis on MRI as controls. For each patient with CR, the signal intensity (SI) of the affected multifidus muscles was measured and compared to that on the contralateral side (signal intensity ratio: SIR). Control patients without CR did not exhibit STIR signal abnormalities in the multifidus muscles. Most of the 18 patients with CR were male (83.3%), and the mean age was 59.4 years. Thirteen of 18 CR patients (72.2%) were determined to have STIR signal abnormalities by a radiologist. The mean SIR in the 13 patients with increased SI was significantly higher than that in the five patients without signal abnormalities (1.23 vs 0.97, P = .004), supporting the radiologist's diagnosis. The distribution of signal abnormalities closely followed those identified via clinical and electrophysiological tests, especially severe weakness (P = .044). Denervation edema of the multifidus muscles can be detected in CR and correlates with clinical/electrophysiological tests and weakness severity, which may aid in CR diagnostics.","Diagnosing cervical radiculopathy (CR) can be difficult because of symptomatic overlap with peripheral neuropathies. In this retrospective observational study, we aimed to determine whether short-tau inversion recovery (STIR) magnetic resonance imaging (MRI) sequences are useful for detecting signs of denervation in the multifidus muscles in patients with CR. We analyzed the data of 18 patients with CR who developed arm weakness within 1 year. We also included 10 patients with sensorimotor symptoms involving the upper extremities who did not have intervertebral foraminal stenosis on MRI as controls. For each patient with CR, the signal intensity (SI) of the affected multifidus muscles was measured and compared to that on the contralateral side (signal intensity ratio: SIR). Control patients without CR did not exhibit STIR signal abnormalities in the multifidus muscles. Most of the 18 patients with CR were male (83.3%), and the mean age was 59.4 years. Thirteen of 18 CR patients (72.2%) were determined to have STIR signal abnormalities by a radiologist. The mean SIR in the 13 patients with increased SI was significantly higher than that in the five patients without signal abnormalities (1.23 vs 0.97, P = .004), supporting the radiologist's diagnosis. The distribution of signal abnormalities closely followed those identified via clinical and electrophysiological tests, especially severe weakness (P = .044). Denervation edema of the multifidus muscles can be detected in CR and correlates with clinical/electrophysiological tests and weakness severity, which may aid in CR diagnostics.","null","null","2021-03","Muscle & Nerve","Muscle & Nerve","Vol.63","No.3","365","370","eng","true","null","scientific_journal","null","null","10.1002/mus.27142","1097-4598","null","null","null","null","null" "Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells","Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells","Keiko Imamura, Yuichiro Yada, Yuishin Izumi, Mitsuya Morita, Akihiro Kawata, Takayo Arisato, Ayako Nagahashi, Takako Enami, Kayoko Tsukita, Hideshi Kawakami, Masanori Nakagawa, Ryosuke Takahashi, Haruhisa Inoue","Keiko Imamura, Yuichiro Yada, Yuishin Izumi, Mitsuya Morita, Akihiro Kawata, Takayo Arisato, Ayako Nagahashi, Takako Enami, Kayoko Tsukita, Hideshi Kawakami, Masanori Nakagawa, Ryosuke Takahashi, Haruhisa Inoue","null","In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence-based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research. ANN NEUROL 2021;89:1226-1233.","In amyotrophic lateral sclerosis (ALS), early diagnosis is essential for both current and potential treatments. To find a supportive approach for the diagnosis, we constructed an artificial intelligence-based prediction model of ALS using induced pluripotent stem cells (iPSCs). Images of spinal motor neurons derived from healthy control subject and ALS patient iPSCs were analyzed by a convolutional neural network, and the algorithm achieved an area under the curve of 0.97 for classifying healthy control and ALS. This prediction model by deep learning algorithm with iPSC technology could support the diagnosis and may provide proactive treatment of ALS through future prospective research. ANN NEUROL 2021;89:1226-1233.","null","null","2021-02-25","Annals of Neurology","Annals of Neurology","Vol.89","No.6","1226","1233","eng","true","null","scientific_journal","null","null","10.1002/ana.26047","1531-8249","null","null","null","null","null" "A new quantitative index in the diagnosis of Parkinson syndrome by dopamine transporter single-photon emission computed tomography.","A new quantitative index in the diagnosis of Parkinson syndrome by dopamine transporter single-photon emission computed tomography.","Ryota Bando, Hideki Otsuka, Tamaki Otani, Noritake Matsuda, Shota Azane, Yamato Kunikane, Yoichi Otomi, Wataru Sako, Yuishin Izumi, Masafumi Harada","Ryota Bando, Hideki Otsuka, Tamaki Otani, Noritake Matsuda, Shota Azane, Yamato Kunikane, Yoichi Otomi, Wataru Sako, Yuishin Izumi, Masafumi Harada","null","Dopamine transporter single-photon emission computed tomography (DAT SPECT) has been widely used to diagnose Parkinson syndrome. Using the standardized uptake value (SUV) of DAT SPECT, we propose ""functional dopamine transporter volume (f-DTV)"" as a new quantitative index to evaluate the three-dimensional volume of functional dopamine transporters and assess its diagnostic ability in differentiating dopaminergic neurodegenerative diseases (dNDD) from non-dNDD. Seventy-nine patients were enrolled (42 dNDD, 37 non-dNDD; 38 men; age 24-88 years). We analyzed seven quantitative indices. The specific binding ratio (SBR) was calculated using a program specialized for DAT SPECT (SBR_Bolt). The SUVmax, SUVpeak, and SUVmean were calculated using a quantification program for bone SPECT. SBR_SUV was calculated by dividing striatal SUVmean by the average of background SUVmean. The cutoff value of the active dopamine transporter level was examined using three methods (threshold of 40% of SUVmax, SUV 2, and SUV 3) to calculate the active dopamine transporter volume (ADV). The f-DTV was calculated by multiplying ADV and SUV. We assessed the correlations between SBR_Bolt and SBR_SUV, and compared the mean value of each index between the dNDD and non-dNDD groups. The abilities of SBR_Bolt, SBR_SUV, SUVmax, SUVpeak, SUVmean, ADV, and f-DTV in differentiating dNDD from non-dNDD were determined by the area under the receiver operating curve (AUC) generated by the receiver operating characteristics analysis. The SBR_Bolt and SBR_SUV highly correlated with each other (r = 0.71). The cutoff value of the active dopamine transporter level was determined as SUV 3. All seven quantitative indices showed lower values in the dNDD group than in the non-dNDD group, and the difference between the two groups was statistically significant (p < 0.05). Sensitivity, specificity, and AUC of f-DTV were slightly lower than those of SBR_Bolt (71%, 79%, and 0.81, respectively, for f-DTV, and 81%, 84%, 0.88, respectively, for SBR_Bolt). The difference in AUC between f-DTV and SBR_Bolt was not statistically significant. This study demonstrates the utility of f-DTV as a novel quantitative index for evaluating the three-dimensional volume of functional dopamine transporters, and that f-DTV has almost the same diagnostic ability to differentiate dNDD from non-dNDD using DAT SPECT.","Dopamine transporter single-photon emission computed tomography (DAT SPECT) has been widely used to diagnose Parkinson syndrome. Using the standardized uptake value (SUV) of DAT SPECT, we propose ""functional dopamine transporter volume (f-DTV)"" as a new quantitative index to evaluate the three-dimensional volume of functional dopamine transporters and assess its diagnostic ability in differentiating dopaminergic neurodegenerative diseases (dNDD) from non-dNDD. Seventy-nine patients were enrolled (42 dNDD, 37 non-dNDD; 38 men; age 24-88 years). We analyzed seven quantitative indices. The specific binding ratio (SBR) was calculated using a program specialized for DAT SPECT (SBR_Bolt). The SUVmax, SUVpeak, and SUVmean were calculated using a quantification program for bone SPECT. SBR_SUV was calculated by dividing striatal SUVmean by the average of background SUVmean. The cutoff value of the active dopamine transporter level was examined using three methods (threshold of 40% of SUVmax, SUV 2, and SUV 3) to calculate the active dopamine transporter volume (ADV). The f-DTV was calculated by multiplying ADV and SUV. We assessed the correlations between SBR_Bolt and SBR_SUV, and compared the mean value of each index between the dNDD and non-dNDD groups. The abilities of SBR_Bolt, SBR_SUV, SUVmax, SUVpeak, SUVmean, ADV, and f-DTV in differentiating dNDD from non-dNDD were determined by the area under the receiver operating curve (AUC) generated by the receiver operating characteristics analysis. The SBR_Bolt and SBR_SUV highly correlated with each other (r = 0.71). The cutoff value of the active dopamine transporter level was determined as SUV 3. All seven quantitative indices showed lower values in the dNDD group than in the non-dNDD group, and the difference between the two groups was statistically significant (p < 0.05). Sensitivity, specificity, and AUC of f-DTV were slightly lower than those of SBR_Bolt (71%, 79%, and 0.81, respectively, for f-DTV, and 81%, 84%, 0.88, respectively, for SBR_Bolt). The difference in AUC between f-DTV and SBR_Bolt was not statistically significant. This study demonstrates the utility of f-DTV as a novel quantitative index for evaluating the three-dimensional volume of functional dopamine transporters, and that f-DTV has almost the same diagnostic ability to differentiate dNDD from non-dNDD using DAT SPECT.","null","null","2021-02-25","Annals of Nuclear Medicine","Annals of Nuclear Medicine","Vol.35","No.4","504","513","eng","true","null","scientific_journal","null","null","10.1007/s12149-021-01592-w","1864-6433","null","null","null","null","null" "Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis","Utility of phrenic nerve ultrasound in amyotrophic lateral sclerosis","CT Suratos, N Takamatsu, Hiroki Yamazaki, Yusuke Osaki, T Fukumoto, Hiroyuki Nodera, Yuishin Izumi","CT Suratos, N Takamatsu, Hiroki Yamazaki, Yusuke Osaki, T Fukumoto, Hiroyuki Nodera, Yuishin Izumi","null","null","null","null","null","2021-02","Acta Neurologica Belgica","Acta Neurologica Belgica","Vol.121","No.1","225","230","eng","true","null","scientific_journal","null","null","10.1007/s13760-020-01531-y","0300-9009","null","null","null","null","null" "Reversible mixed perfusion on 123 I-IMP SPECT in anti-AMPA receptor encephalitis: A case report","Reversible mixed perfusion on 123 I-IMP SPECT in anti-AMPA receptor encephalitis: A case report","T Fukumoto, Ryosuke Miyamoto, Koji Fujita, N Murakami, Naoko Matsui, Yuishin Izumi","T Fukumoto, Ryosuke Miyamoto, Koji Fujita, N Murakami, Naoko Matsui, Yuishin Izumi","null","null","null","null","null","2021-01-04","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.421","null","117306","117306","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2020.117306","1878-5883","null","null","null","null","null" "Genetic and functional analysis of KIF5A variants in Japanese patients with sporadic amyotrophic lateral sclerosis","Genetic and functional analysis of KIF5A variants in Japanese patients with sporadic amyotrophic lateral sclerosis","R Nakamura, G Tohnai, N Atsuta, M Nakatochi, N Hayashi, H Watanabe, D Yokoi, H Watanabe, M Katsuno, Yuishin Izumi, A Taniguchi, K Kanai, M Morita, O Kano, S Kuwabara, M Oda, K Abe, M Aoki, I Aiba, K Okamoto, K Mizoguchi, N Hattori, K Nakashima, Ryuji Kaji, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)","R Nakamura, G Tohnai, N Atsuta, M Nakatochi, N Hayashi, H Watanabe, D Yokoi, H Watanabe, M Katsuno, Yuishin Izumi, A Taniguchi, K Kanai, M Morita, O Kano, S Kuwabara, M Oda, K Abe, M Aoki, I Aiba, K Okamoto, K Mizoguchi, N Hattori, K Nakashima, Ryuji Kaji, G Sobue, Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)","null","Two recent genetic studies reported that loss-of-function mutation of the C-terminal cargo-binding tail domain of the KIF5A gene cause amyotrophic lateral sclerosis (ALS). The aim of this study is to investigate the frequency of KIF5A variants in Japanese patients with sporadic ALS. In total, 807 sporadic ALS patients and 191 normal controls from a multicenter ALS cohort in Japan were included. Whole exome sequencing on an Illumina HiSeq 2000/2500 sequencer was used to identify and select variants within the KIF5A gene. Thirteen patients harbored a nonsynonymous variant in the KIF5A gene; These were considered variants of uncertain significance. One patient harbored a novel splice-site variant (c.2993-3C>A) in the C-terminal cargo-binding tail domain of the KIF5A gene. Functional analysis of this variant revealed that it caused skipping of exon 27. The frequency of KIF5A mutations in Japanese patients with sporadic ALS was 0.12% (1/807). This study reports a novel loss-of-function variant in KIF5A, and indicates that loss-of-function variant in KIF5A is a rare cause of sporadic ALS in Japanese patients.","Two recent genetic studies reported that loss-of-function mutation of the C-terminal cargo-binding tail domain of the KIF5A gene cause amyotrophic lateral sclerosis (ALS). The aim of this study is to investigate the frequency of KIF5A variants in Japanese patients with sporadic ALS. In total, 807 sporadic ALS patients and 191 normal controls from a multicenter ALS cohort in Japan were included. Whole exome sequencing on an Illumina HiSeq 2000/2500 sequencer was used to identify and select variants within the KIF5A gene. Thirteen patients harbored a nonsynonymous variant in the KIF5A gene; These were considered variants of uncertain significance. One patient harbored a novel splice-site variant (c.2993-3C>A) in the C-terminal cargo-binding tail domain of the KIF5A gene. Functional analysis of this variant revealed that it caused skipping of exon 27. The frequency of KIF5A mutations in Japanese patients with sporadic ALS was 0.12% (1/807). This study reports a novel loss-of-function variant in KIF5A, and indicates that loss-of-function variant in KIF5A is a rare cause of sporadic ALS in Japanese patients.","null","null","2021-01","Neurobiology of Aging","Neurobiology of Aging","Vol.97","No.147","e11","e17","eng","true","null","scientific_journal","null","null","10.1016/j.neurobiolaging.2020.07.010","0197-4580","null","null","null","null","null" "Ataxia with vitamin E deficiency in the Philippines: A case report of two siblings.","Ataxia with vitamin E deficiency in the Philippines: A case report of two siblings.","Daisy Ma Tabuena, Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Nobuaki Yamamoto, Kazuhisa Miyake, Taku Matsuda, Yuishin Izumi, Yasushi Takagi, P Rollin Tabuena, Toshitaka Kawarai","Daisy Ma Tabuena, Ryoma Morigaki, Ryosuke Miyamoto, Hideo Mure, Nobuaki Yamamoto, Kazuhisa Miyake, Taku Matsuda, Yuishin Izumi, Yasushi Takagi, P Rollin Tabuena, Toshitaka Kawarai","null","Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.","Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3.4","400","403","eng","true","null","scientific_journal","null","null","10.2152/jmi.68.400","1349-6867","null","null","null","null","null" "神経超音波を用いた症状誘発肢位での動的評価が診断の一助となった真の神経原性胸部出口症候群の1例","神経超音波を用いた症状誘発肢位での動的評価が診断の一助となった真の神経原性胸部出口症候群の1例","山﨑 博輝, 高松 直子, 野寺 裕之, 松田 拓, 牟礼 英生, 安田 宗義, 和泉 唯信","Hiroki Yamazaki, 高松 直子, Hiroyuki Nodera, Taku Matsuda, Hideo Mure, 安田 宗義, Yuishin Izumi","null","null","null","null","null","2021","臨床神経生理学","Japanese Journal of Clinical Neurophysiology","Vol.49","No.6","85","88","jpn","true","null","scientific_journal","null","null","null","1345-7101","null","null","null","null","null" "Clinical uses of a robot (hybrid-assisted limb or HALTM)in patients with post-stroke spasticity after botulinum toxin injections","Clinical uses of a robot (hybrid-assisted limb or HALTM)in patients with post-stroke spasticity after botulinum toxin injections","Tsuyoshi Okuno, T Takeuchi, E Takeda, Yuishin Izumi, Ryuji Kaji","Tsuyoshi Okuno, T Takeuchi, E Takeda, Yuishin Izumi, Ryuji Kaji","null","Spasticity is the major cause of disabilities in stroke-survivors. Botulinum neurotoxin (BoNT) injections have been used to reduce the muscle tone in those patients, but its efficacy in functional outcome is not well delineated. We have studied the effect of a robot (Hybrid-Assisted Limb or HAL™) designed for assisting the elbow flexion and extension in those who underwent BoNT injections with reduced muscle tone. We enrolled 15 post stroke patients who had BoNT injections for more than 12 months. They were measured for active ROM (range of motion) with video recordings before and after the use of HAL for 40 minutes. Active ROM was measured by a rater who were blinded as to the use of the robot. Significant increase of active ROM was observed immediately after the use of HAL, and the effect was maintained for another 12 months by repeating the sessions. It is suggested from present study that the combined use of BoNT and robotics is effective efficacious for regaining the active function of the upper limb in stroke survivors. J. Med. Invest. 68 : 297-301, August, 2021.","Spasticity is the major cause of disabilities in stroke-survivors. Botulinum neurotoxin (BoNT) injections have been used to reduce the muscle tone in those patients, but its efficacy in functional outcome is not well delineated. We have studied the effect of a robot (Hybrid-Assisted Limb or HAL™) designed for assisting the elbow flexion and extension in those who underwent BoNT injections with reduced muscle tone. We enrolled 15 post stroke patients who had BoNT injections for more than 12 months. They were measured for active ROM (range of motion) with video recordings before and after the use of HAL for 40 minutes. Active ROM was measured by a rater who were blinded as to the use of the robot. Significant increase of active ROM was observed immediately after the use of HAL, and the effect was maintained for another 12 months by repeating the sessions. It is suggested from present study that the combined use of BoNT and robotics is effective efficacious for regaining the active function of the upper limb in stroke survivors. J. Med. Invest. 68 : 297-301, August, 2021.","null","null","2021","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.68","No.3,4","297","301","eng","true","null","scientific_journal","null","null","10.2152/jmi.68.297","1349-6867","null","null","null","null","null" "筋萎縮性側索硬化症(ALS)を疑う神経症候とその特徴 筋力低下,体のぴくつき","筋萎縮性側索硬化症(ALS)を疑う神経症候とその特徴 筋力低下,体のぴくつき","和泉 唯信, 福島 功士, 沖 良祐","Yuishin Izumi, 福島 功士, Ryosuke Oki","null","null","null","null","null","2020-12-10","Medicina","Medicina","Vol.57","No.13","2354","2357","jpn","true","null","scientific_journal","null","null","10.11477/mf.1402227359","0025-7699","null","https://search.jamas.or.jp/link/ui/2021080649","null","null","null" "言語聴覚士 脳神経内科を標榜する療養型病床における言語聴覚士の役割","言語聴覚士 脳神経内科を標榜する療養型病床における言語聴覚士の役割","伊藤 一慶, 丸川 章, 織田 雅也, 和泉 唯信","伊藤 一慶, 丸川 章, 織田 雅也, Yuishin Izumi","null","null","null","null","null","2020-11","難病と在宅ケア","Home Health Care for the People with Intractable Diseases","Vol.26","No.8","41","44","jpn","true","null","scientific_journal","null","null","null","1880-9200","null","https://ci.nii.ac.jp/naid/40022392417/","null","null","null" "Factors associated with DWI-ASPECTS score in patients with acute ischemic stroke due to cerebral large vessel occlusion","Factors associated with DWI-ASPECTS score in patients with acute ischemic stroke due to cerebral large vessel occlusion","Nobuaki Yamamoto, Yuishin Izumi, Yuki Yamamoto, K Kuroda, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yasushi Takagi","Nobuaki Yamamoto, Yuishin Izumi, Yuki Yamamoto, K Kuroda, Izumi Yamaguchi, Shu Sogabe, Takeshi Miyamoto, Kenji Shimada, Yasuhisa Kanematsu, Ryoma Morigaki, Yasushi Takagi","null","The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission. We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings. This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p < 0.001, odds ratio 0.31, p = 0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission.","The Alberta Stroke Program Early CT score (ASPECTS) of patients with acute ischemic stroke at the time of admission varies. It is crucial to select appropriate methods of treatment, such as recombinant tissue-plasminogen activator, and/or endovascular thrombectomy. According to the recent guidelines, endovascular thrombectomy for patients with large vessel occlusion (LVO) and lesion of ischemic tissue that was not yet infarcted is effective. This result demonstrates the importance of patient selection based on neuroradiological imaging. However, there are many patients who are judged as ineligibility for recanalization therapy because of presence of large ischemic core, indicating unfavorable ASPECTS, at the time of admission. We investigated the factors associated with favorable diffusion-weighted image (DWI)-ASPECTS score at the time of admission. We studies patients with LVO within 24 h from onset who were admitted into our hospital. We divided them into two groups, with favorable DWI-ASPECTS (≥6), and unfavorable DWI-ASPECTS (<6) at the time of admission. We investigated factors associated with favorable DWI-ASPECTS by evaluation of our patients' severity of clinical symptom, etiology, and radiological findings. This study showed that mild white matter lesion (Fazekas scale ≤1), absence of internal carotid artery (ICA) occlusion and cardioembolic stroke were independent factor of favorable DWI-ASPECTS at the time of admission. (odds ratio 12.92, p < 0.001, odds ratio 0.31, p = 0.001, odds ratio 0.16, p = 0.001, respectively) CONCLUSIONS: Absence of severe white matter lesion, cardioembolic stroke, and ICA occlusion might be associated with favorable DWI-ASPECTS at the time of admission.","null","null","2020-10-16","Clinical Neurology and Neurosurgery","Clinical Neurology and Neurosurgery","Vol.199","null","106316","106316","eng","true","null","scientific_journal","null","null","10.1016/j.clineuro.2020.106316","1872-6968","null","null","null","null","null" "Neuropsychiatric systemic lupus erythematosus with cerebellar vasculitis and obstructive hydrocephalus requiring decompressive craniectomy.","Neuropsychiatric systemic lupus erythematosus with cerebellar vasculitis and obstructive hydrocephalus requiring decompressive craniectomy.","Nobuhito Naito, Hiroshi Kawano, Yuya Yamashita, Mayo Kondou, Shotaro Haji, Ryosuke Miyamoto, Yuko Toyoda, Yasuhisa Kanematsu, Yuishin Izumi, Yoshimi Bando, Yasuhiko Nishioka","Nobuhito Naito, Hiroshi Kawano, Yuya Yamashita, Mayo Kondou, Shotaro Haji, Ryosuke Miyamoto, Yuko Toyoda, Yasuhisa Kanematsu, Yuishin Izumi, Yoshimi Bando, Yasuhiko Nishioka","null","A 36-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE) was admitted to our hospital due to increasing disease SLE activity. Despite the intensification of immunosuppressive treatment, headache newly developed and worsened. Magnetic resonance imaging (MRI) revealed spreading of a high-intensity area along the sulci of the bilateral cerebellar hemispheres. She was diagnosed with neuropsychiatric SLE and methylprednisolone (mPSL) pulse therapy was started. However, consciousness disorder due to cerebellar oedema with obstructive hydrocephalus appeared and required decompressive craniectomy. The histological findings of the biopsy specimens from cerebellar vermis were compatible with features of vasculitis. She was successfully treated adding intravenous cyclophosphamide therapy.","A 36-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE) was admitted to our hospital due to increasing disease SLE activity. Despite the intensification of immunosuppressive treatment, headache newly developed and worsened. Magnetic resonance imaging (MRI) revealed spreading of a high-intensity area along the sulci of the bilateral cerebellar hemispheres. She was diagnosed with neuropsychiatric SLE and methylprednisolone (mPSL) pulse therapy was started. However, consciousness disorder due to cerebellar oedema with obstructive hydrocephalus appeared and required decompressive craniectomy. The histological findings of the biopsy specimens from cerebellar vermis were compatible with features of vasculitis. She was successfully treated adding intravenous cyclophosphamide therapy.","null","null","2020-10-09","Modern Rheumatology Case Reports","Modern Rheumatology Case Reports","Vol.5","No.1","52","57","eng","true","null","scientific_journal","null","null","10.1080/24725625.2020.1826626","2472-5625","null","null","null","null","null" "Prediction of improvement after extended thymectomy in non-thymomatous myasthenia gravis patients","Prediction of improvement after extended thymectomy in non-thymomatous myasthenia gravis patients","M Yoshida, K Kondo, Naoko Matsui, Yuishin Izumi, Y Bando, M Yokoishi, K Kajiura, Akira Tangoku","M Yoshida, K Kondo, Naoko Matsui, Yuishin Izumi, Y Bando, M Yokoishi, K Kajiura, Akira Tangoku","null","It is popularly believed that myasthenia gravis (MG) patients show acetylcholine receptor antibody (AChRAb) production associated with the thymus (germinal centers, approximately 80%). It has been suggested that thymectomy can remove the area of autoantibody production. This study aimed to determine whether the solid volume of the thymus calculated using three-dimensional (3D) imaging could be used to predict the efficacy of thymectomy. Additionally, the study assessed the relationships of the solid volume with germinal centers, change in the serum AChRAb level, postoperative MG improvement, and prednisolone (PSL) dose reduction extent. This retrospective study included 12 consecutive non-thymomatous MG patients (9 female and 3 male patients), who underwent extended thymectomy at our institution over the last 10 years. The mean patient age was 43.3 ± 14.2 years (range, 12-59 years). The study assessed the number of germinal centers per unit area, change in the serum AChRAb level, postoperative MG improvement, PSL dose reduction extent, and solid volume of the thymus. The number of germinal centers per unit area was significantly correlated with the solid volume of the thymus. The PSL dose reduction extent tended to be correlated with the solid volume. Our findings suggest that the solid volume of the thymus can possibly predict steroid dose reduction. Additionally, the solid volume of the thymus in 3D images is the most important indicator for predicting the efficacy of extended thymectomy.","It is popularly believed that myasthenia gravis (MG) patients show acetylcholine receptor antibody (AChRAb) production associated with the thymus (germinal centers, approximately 80%). It has been suggested that thymectomy can remove the area of autoantibody production. This study aimed to determine whether the solid volume of the thymus calculated using three-dimensional (3D) imaging could be used to predict the efficacy of thymectomy. Additionally, the study assessed the relationships of the solid volume with germinal centers, change in the serum AChRAb level, postoperative MG improvement, and prednisolone (PSL) dose reduction extent. This retrospective study included 12 consecutive non-thymomatous MG patients (9 female and 3 male patients), who underwent extended thymectomy at our institution over the last 10 years. The mean patient age was 43.3 ± 14.2 years (range, 12-59 years). The study assessed the number of germinal centers per unit area, change in the serum AChRAb level, postoperative MG improvement, PSL dose reduction extent, and solid volume of the thymus. The number of germinal centers per unit area was significantly correlated with the solid volume of the thymus. The PSL dose reduction extent tended to be correlated with the solid volume. Our findings suggest that the solid volume of the thymus can possibly predict steroid dose reduction. Additionally, the solid volume of the thymus in 3D images is the most important indicator for predicting the efficacy of extended thymectomy.","null","null","2020-10-05","PLoS ONE","PLoS ONE","Vol.15","No.10","e0239756","e0239756","eng","true","null","scientific_journal","null","null","10.1371/journal.pone.0239756","1932-6203","null","null","null","null","null" "A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis","A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis","R Nakamura, K Misawa, G Tohnai, M Nakatochi, S Furuhashi, N Atsuta, N Hayashi, D Yokoi, H Watanabe, M Katsuno, Yuishin Izumi, K Kanai, N Hattori, M Morita, A Taniguchi, O Kano, M Oda, K Shibuya, S Kuwabara, N Suzuki, M Aoki, Y Ohta, T Yamashita, K Abe, R Hashimoto, I Aiba, K Okamoto, K Mizoguchi, K Hasegawa, Y Okada, T Ishihara, O Onodera, K Nakashima, Ryuji Kaji, Y Kamatani, S Ikegawa, Y Momozawa, M Kubo, N Ishida, N Minegishi, M Nagasaki, G Sobue","R Nakamura, K Misawa, G Tohnai, M Nakatochi, S Furuhashi, N Atsuta, N Hayashi, D Yokoi, H Watanabe, M Katsuno, Yuishin Izumi, K Kanai, N Hattori, M Morita, A Taniguchi, O Kano, M Oda, K Shibuya, S Kuwabara, N Suzuki, M Aoki, Y Ohta, T Yamashita, K Abe, R Hashimoto, I Aiba, K Okamoto, K Mizoguchi, K Hasegawa, Y Okada, T Ishihara, O Onodera, K Nakashima, Ryuji Kaji, Y Kamatani, S Ikegawa, Y Momozawa, M Kubo, N Ishida, N Minegishi, M Nagasaki, G Sobue","null","Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.","Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.","null","null","2020-09-23","Communications Biology","Communications Biology","Vol.3","No.1","526","526","eng","true","null","scientific_journal","null","null","10.1038/s42003-020-01251-2","2399-3642","null","null","null","null","null" "Efficacy of Istradefylline for the Treatment of ADCY5-Related Disease","Efficacy of Istradefylline for the Treatment of ADCY5-Related Disease","Ryosuke Miyamoto, Toshitaka Kawarai, T Takeuchi, Yuishin Izumi, Satoshi Goto, Ryuji Kaji","Ryosuke Miyamoto, Toshitaka Kawarai, T Takeuchi, Yuishin Izumi, Satoshi Goto, Ryuji Kaji","null","View Supplementary Video 1 View Supplementary Video 2.","View Supplementary Video 1 View Supplementary Video 2.","null","null","2020-09-07","Movement Disorders Clinical Practice","Movement Disorders Clinical Practice","Vol.7","No.7","852","853","eng","true","null","scientific_journal","null","null","10.1002/mdc3.13067","2330-1619","null","null","null","null","null" "腕神経叢エコー検査が契機となって悪性腫瘍が診断できた1例","A case of led to diagnosis of malignancy by brachial plexus ultrasonography","高松 直子, 大崎 裕亮, 山﨑 博輝, 黒田 一駿, 小川 博久, 上原 久典, 常山 幸一, 野寺 裕之, 和泉 唯信","高松 直子, Yusuke Osaki, Hiroki Yamazaki, Kazutaka Kuroda, Hirohisa Ogawa, Hisanori Uehara, Koichi Tsuneyama, Hiroyuki Nodera, Yuishin Izumi","null","A 72-year-old man admitted to our hospital due to severe pain and drop hand in the left arm. MRI and CT of the head and neck at an outside hospital showed no abnormality. Neurological findings revealed distal weakness in the left upper extremity, vague pain between the radial aspect of the left hand and the middle of the digits 1-3, as well as brisk reflexes in the left extremities. Small masses were palpable in the posterior neck, the lower jaw, and the left neck. Clinically, left radial neuropathy and cervical radiculopathy were suspected. We performed ultrasound of the nerve roots, brachial plexus, and the radial nerve. There was a mass compressing the left brachial plexus from the caudolateral direction. Additionally, nerve swelling in the left arm was identified. Skin biopsy over the mass suggested metastatic adenocarcinoma. Chest CT scan showed a mass in the upper right lobe suggestive of a lung cancer. We concluded that the pain was due to radial neuropathy and upper and middle trunk disturbance of the left brachial plexopathy, of which neuromuscular ultrasound was useful in diagnosis.","A 72-year-old man admitted to our hospital due to severe pain and drop hand in the left arm. MRI and CT of the head and neck at an outside hospital showed no abnormality. Neurological findings revealed distal weakness in the left upper extremity, vague pain between the radial aspect of the left hand and the middle of the digits 1-3, as well as brisk reflexes in the left extremities. Small masses were palpable in the posterior neck, the lower jaw, and the left neck. Clinically, left radial neuropathy and cervical radiculopathy were suspected. We performed ultrasound of the nerve roots, brachial plexus, and the radial nerve. There was a mass compressing the left brachial plexus from the caudolateral direction. Additionally, nerve swelling in the left arm was identified. Skin biopsy over the mass suggested metastatic adenocarcinoma. Chest CT scan showed a mass in the upper right lobe suggestive of a lung cancer. We concluded that the pain was due to radial neuropathy and upper and middle trunk disturbance of the left brachial plexopathy, of which neuromuscular ultrasound was useful in diagnosis.","null","null","2020-08","神経超音波医学","Neurosonology","Vol.33","No.2","36","40","jpn","true","null","scientific_journal","null","null","10.2301/neurosonology.33.36","0917-074X","null","https://ci.nii.ac.jp/naid/130007908511/","null","null","null" "Cerebral Venous Thrombosis: An Unexpected Complication with Cerebrospinal Fluid Leaks after a Fall in a Patient with Spinocerebellar Ataxia Type 6.","Cerebral Venous Thrombosis: An Unexpected Complication with Cerebrospinal Fluid Leaks after a Fall in a Patient with Spinocerebellar Ataxia Type 6.","Yamamoto Yuki, Nobuaki Yamamoto, Koji Fujita, Fukumoto Tatsuya, Murakami Nagahisa, Hideo Mure, Yasuhisa Kanematsu, Yasushi Takagi, Yuishin Izumi","Yamamoto Yuki, Nobuaki Yamamoto, Koji Fujita, Fukumoto Tatsuya, Murakami Nagahisa, Hideo Mure, Yasuhisa Kanematsu, Yasushi Takagi, Yuishin Izumi","null","null","null","null","null","2020-04","Internal Medicine","Internal Medicine","Vol.59","No.14","1749","1753","eng","true","null","scientific_journal","null","null","10.2169/internalmedicine.4388-20","0918-2918","null","null","null","null","null" "Cognitive and Behavioral Status in Japanese ALS Patients: A Multicenter Study","Cognitive and Behavioral Status in Japanese ALS Patients: A Multicenter Study","Y Watanabe, J Raaphorst, Yuishin Izumi, H Yoshino, S Ito, T Adachi, H Takigawa, M Masuda, N Atsuta, Y Adachi, S Isose, K Arai, O Yokota, M Oda, M Ogino, H Ichikawa, K Hasegawa, H Kimura, T Shimizu, I Aiba, H Yabe, M Kanba, K Kusumi, T Aoki, Y Hiroe, H Watanabe, K Nishiyama, M Nomoto, G Sobue, E Beeldman, R Hanajima, K Nakashima, group research ALS-FTD-Q-J","Y Watanabe, J Raaphorst, Yuishin Izumi, H Yoshino, S Ito, T Adachi, H Takigawa, M Masuda, N Atsuta, Y Adachi, S Isose, K Arai, O Yokota, M Oda, M Ogino, H Ichikawa, K Hasegawa, H Kimura, T Shimizu, I Aiba, H Yabe, M Kanba, K Kusumi, T Aoki, Y Hiroe, H Watanabe, K Nishiyama, M Nomoto, G Sobue, E Beeldman, R Hanajima, K Nakashima, group research ALS-FTD-Q-J","null","Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression. Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests. Caregivers were asked to complete the ALS-FTD-Questionnaire (ALS-FTD-Q), a behavioral screen. We defined severe cognitive impairment (MoCA < 21 or FAB < 11), mild impairment (11 ≤ MoCA ≤ 25 or 11 ≤ FAB ≤ 15), and normal cognition (MoCA > 25 or FAB > 15). Severe and mild behavioral impairments and normal behavior were defined by the ALS-FTD-Q scores. In 145 ALS patients, better cognitive scores were correlated with earlier age at onset, whereas a worse behavioral score was associated with a longer disease duration and higher level of anxiety and depression. Around seventy percent of all ALS patients showed mild (40-45%) or severe cognitive impairment with cognitive impairment outnumbering behavioral impairment fivefold. Cognitive functions were more impaired in patients with age of onset over 65 years, while behavioral scores were not related to age. Considering the high prevalence of in particular cognitive impairment, and the diversity of impairments, the cognitive and behavioral aspects of Japanese ALS patients should be given more attention clinically.","Amyotrophic lateral sclerosis (ALS) patients may present with cognitive and behavioral abnormalities similar to frontotemporal dementia (FTD). In this multicenter study we examined Japanese ALS patients with and without FTD in order to characterize the full extent of cognitive and behavioral abnormalities, including associations with functional motor status, anxiety and depression. Patients were evaluated using the Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Hospital Anxiety and Depression Scale, ALS Functional Rating Scale-Revised, spirometry, and verbal fluency tests. Caregivers were asked to complete the ALS-FTD-Questionnaire (ALS-FTD-Q), a behavioral screen. We defined severe cognitive impairment (MoCA < 21 or FAB < 11), mild impairment (11 ≤ MoCA ≤ 25 or 11 ≤ FAB ≤ 15), and normal cognition (MoCA > 25 or FAB > 15). Severe and mild behavioral impairments and normal behavior were defined by the ALS-FTD-Q scores. In 145 ALS patients, better cognitive scores were correlated with earlier age at onset, whereas a worse behavioral score was associated with a longer disease duration and higher level of anxiety and depression. Around seventy percent of all ALS patients showed mild (40-45%) or severe cognitive impairment with cognitive impairment outnumbering behavioral impairment fivefold. Cognitive functions were more impaired in patients with age of onset over 65 years, while behavioral scores were not related to age. Considering the high prevalence of in particular cognitive impairment, and the diversity of impairments, the cognitive and behavioral aspects of Japanese ALS patients should be given more attention clinically.","null","null","2020-03","Journal of Neurology","Journal of Neurology","Vol.267","No.5","1321","1330","eng","true","null","scientific_journal","null","null","10.1007/s00415-019-09655-9","1432-1459","null","null","null","null","null" "Prognosis of Amyotrophic Lateral Sclerosis Patients Undergoing Tracheostomy Invasive Ventilation Therapy in Japan","Prognosis of Amyotrophic Lateral Sclerosis Patients Undergoing Tracheostomy Invasive Ventilation Therapy in Japan","N Hayashi, N Atsuta, D Yokoi, R Nakamura, M Nakatochi, M Katsuno, Yuishin Izumi, K Kanai, N Hattori, A Taniguchi, M Morita, O Kano, K Shibuya, S Kuwabara, N Suzuki, M Aoki, I Aiba, K Mizoguchi, M Oda, Ryuji Kaji, G Sobue","N Hayashi, N Atsuta, D Yokoi, R Nakamura, M Nakatochi, M Katsuno, Yuishin Izumi, K Kanai, N Hattori, A Taniguchi, M Morita, O Kano, K Shibuya, S Kuwabara, N Suzuki, M Aoki, I Aiba, K Mizoguchi, M Oda, Ryuji Kaji, G Sobue","null","The aim of this study is to describe and clarify the factors affecting the prognosis of Japanese patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy invasive ventilation (TIV) therapy. We conducted a prospective longitudinal observational case-control study using a multicentre registry. ALS patients who started TIV therapy after registration (TIV group) and those who did not receive TIV (non-TIV group) were included. We compared the survival time between the TIV group and the non-TIV group using a propensity score matching analysis and evaluated the prognostic factors in the TIV group. From February 2006 to January 2018, 190 patients in the TIV group and 1093 patients in the non-TIV group were included in this study. The mean age of disease onset and usage rate of gastrostomy and non-invasive ventilation therapy differed between the groups. In the propensity score matching analysis using known prognostic factors, the median overall survival time of the TIV group was significantly greater than that of the non-TIV group (11.33 years vs 4.61 years; p<0.001). Analysis using the Cox proportional hazard model suggested that older age of onset and respiratory onset was an independent factor for poor prognosis after starting TIV therapy. We showed that there was a significant difference of approximately 7 years in life expectancy between Japanese ALS patients who did and did not receive TIV therapy.","The aim of this study is to describe and clarify the factors affecting the prognosis of Japanese patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy invasive ventilation (TIV) therapy. We conducted a prospective longitudinal observational case-control study using a multicentre registry. ALS patients who started TIV therapy after registration (TIV group) and those who did not receive TIV (non-TIV group) were included. We compared the survival time between the TIV group and the non-TIV group using a propensity score matching analysis and evaluated the prognostic factors in the TIV group. From February 2006 to January 2018, 190 patients in the TIV group and 1093 patients in the non-TIV group were included in this study. The mean age of disease onset and usage rate of gastrostomy and non-invasive ventilation therapy differed between the groups. In the propensity score matching analysis using known prognostic factors, the median overall survival time of the TIV group was significantly greater than that of the non-TIV group (11.33 years vs 4.61 years; p<0.001). Analysis using the Cox proportional hazard model suggested that older age of onset and respiratory onset was an independent factor for poor prognosis after starting TIV therapy. We showed that there was a significant difference of approximately 7 years in life expectancy between Japanese ALS patients who did and did not receive TIV therapy.","null","null","2020-03","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","Vol.91","No.3","285","290","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2019-322213","1468-330X","null","null","null","null","null" "Differences in Cerebellar Perfusion Between Parkinson's Disease and Multiple System Atrophy","Differences in Cerebellar Perfusion Between Parkinson's Disease and Multiple System Atrophy","Nagahisa Murakami, Wataru Sako, Shotaroh Haji, T Furukawa, Y Otomi, H Otsuka, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Nagahisa Murakami, Wataru Sako, Shotaroh Haji, T Furukawa, Y Otomi, H Otsuka, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Objective biomarkers are required for differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). We aimed to determine if cerebellar blood flow, measured using N-isopropyl-[I] p-iodoamphetamine single photon emission computed tomography (I -IMP-SPECT), was useful for differentiating between PD, MSA and PSP. Twenty-four patients with PD, seventeen patients with MSA with predominant parkinsonian features (MSA-P), sixteenth patients with MSA with predominant cerebellar ataxia (MSA-C) and eight patients with PSP were enrolled. Twenty-seven normal controls' data were used for the calculation of z score. All patients underwent I -IMP-SPECT, and data were analyzed using a three-dimensional-stereotactic surface projection program. Cerebellar perfusion in MSA-P (MSA-P vs PD, P = .002; MSA-P vs PSP, P < .001) and MSA-C (MSA-C vs PD, P < .001; MSA-C vs PSP, P < .001) were significantly decreased compared with PD or PSP. There was no significant difference in perfusion between PD and PSP groups (P = .061). The area under the receiver operating characteristic curve for cerebellar perfusion between MSA-P and PD was 0.858. Our findings revealed that cerebellar perfusion by I-IMP-SPECT was useful for differentiating between PD and MSA-P.","Objective biomarkers are required for differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). We aimed to determine if cerebellar blood flow, measured using N-isopropyl-[I] p-iodoamphetamine single photon emission computed tomography (I -IMP-SPECT), was useful for differentiating between PD, MSA and PSP. Twenty-four patients with PD, seventeen patients with MSA with predominant parkinsonian features (MSA-P), sixteenth patients with MSA with predominant cerebellar ataxia (MSA-C) and eight patients with PSP were enrolled. Twenty-seven normal controls' data were used for the calculation of z score. All patients underwent I -IMP-SPECT, and data were analyzed using a three-dimensional-stereotactic surface projection program. Cerebellar perfusion in MSA-P (MSA-P vs PD, P = .002; MSA-P vs PSP, P < .001) and MSA-C (MSA-C vs PD, P < .001; MSA-C vs PSP, P < .001) were significantly decreased compared with PD or PSP. There was no significant difference in perfusion between PD and PSP groups (P = .061). The area under the receiver operating characteristic curve for cerebellar perfusion between MSA-P and PD was 0.858. Our findings revealed that cerebellar perfusion by I-IMP-SPECT was useful for differentiating between PD and MSA-P.","null","null","2020-02-15","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.409","null","116627","116627","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2019.116627","1878-5883","null","null","null","null","null" "Successful treatment of progressive multifocal leukoencephalopathy with mirtazapine and mefloquine in refractory myeloma","Successful treatment of progressive multifocal leukoencephalopathy with mirtazapine and mefloquine in refractory myeloma","Kengo Udaka, Shingen Nakamura, Shiroh Fujii, Ryosuke Miyamoto, Naoko Matsui, Shiyori Kawata, Taiki Hori, Junpei Murai, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Takeshi Harada, Kumiko Kagawa, Yuishin Izumi, Masahiro Abe, Hirokazu Miki","Kengo Udaka, Shingen Nakamura, Shiroh Fujii, Ryosuke Miyamoto, Naoko Matsui, Shiyori Kawata, Taiki Hori, Junpei Murai, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Mamiko Takahashi, Takeshi Harada, Kumiko Kagawa, Yuishin Izumi, Masahiro Abe, Hirokazu Miki","null","null","null","null","null","2020","International Journal of Myeloma","International Journal of Myeloma","Vol.10","No.1","8","12","eng","true","null","scientific_journal","null","null","null","2187-3143","null","null","null","null","null" "Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients","Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients","K Imamura, Yuishin Izumi, H Banno, R Uozumi, S Morita, N Egawa, T Ayaki, M Nagai, K Nishiyama, Y Watanabe, R Hanajima, R Oki, K Fujita, N Takahashi, T Ikeda, A Shimizu, A Morinaga, T Hirohashi, Y Fujii, R Takahashi, H Inoue","K Imamura, Yuishin Izumi, H Banno, R Uozumi, S Morita, N Egawa, T Ayaki, M Nagai, K Nishiyama, Y Watanabe, R Hanajima, R Oki, K Fujita, N Takahashi, T Ikeda, A Shimizu, A Morinaga, T Hirohashi, Y Fujii, R Takahashi, H Inoue","null","Amyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS. The objectives of this study are to evaluate the safety and tolerability of bosutinib for the treatment of patients with ALS and to explore the efficacy of bosutinib on ALS. This study is the first clinical trial of administered bosutinib for patients with ALS. An open-label, multicentre phase I dose escalation study has been designed. The study consists of a 12-week observation period, a 1-week transitional period, a 12-week study treatment period and a 4-week follow-up period. After completion of the transitional period, subjects whose total ALS Functional Rating Scale-Revised (ALSFRS-R) score decreased by 1-3 points during the 12-week observation period receive bosutinib for 12 weeks. Three to six patients with ALS are enrolled in each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day) to evaluate the safety and tolerability under a 3+3 dose escalation study design. Dose escalation and maximum tolerated dose are determined by the safety assessment committee comprising oncologists/haematologists and neurologists based on the incidence of dose-limiting toxicity in the first 4 weeks of the treatment at each dose level. A recommended phase II dose is determined by the safety assessment committee on completion of the 12-week study treatment in all subjects at all dose levels. The efficacy of bosutinib is also evaluated exploratorily using ALS clinical scores and biomarkers. This study received full ethical approval from the institutional review board of each participating site. The findings of the study will be disseminated in peer-reviewed journals and at scientific conferences. UMIN000036295; Pre-results, JMA-IIA00419; Pre-results.","Amyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS. The objectives of this study are to evaluate the safety and tolerability of bosutinib for the treatment of patients with ALS and to explore the efficacy of bosutinib on ALS. This study is the first clinical trial of administered bosutinib for patients with ALS. An open-label, multicentre phase I dose escalation study has been designed. The study consists of a 12-week observation period, a 1-week transitional period, a 12-week study treatment period and a 4-week follow-up period. After completion of the transitional period, subjects whose total ALS Functional Rating Scale-Revised (ALSFRS-R) score decreased by 1-3 points during the 12-week observation period receive bosutinib for 12 weeks. Three to six patients with ALS are enrolled in each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day) to evaluate the safety and tolerability under a 3+3 dose escalation study design. Dose escalation and maximum tolerated dose are determined by the safety assessment committee comprising oncologists/haematologists and neurologists based on the incidence of dose-limiting toxicity in the first 4 weeks of the treatment at each dose level. A recommended phase II dose is determined by the safety assessment committee on completion of the 12-week study treatment in all subjects at all dose levels. The efficacy of bosutinib is also evaluated exploratorily using ALS clinical scores and biomarkers. This study received full ethical approval from the institutional review board of each participating site. The findings of the study will be disseminated in peer-reviewed journals and at scientific conferences. UMIN000036295; Pre-results, JMA-IIA00419; Pre-results.","null","null","2019-12-02","BMJ Open","BMJ Open","Vol.9","No.12","e033131","e033131","eng","true","null","scientific_journal","null","null","10.1136/bmjopen-2019-033131","2044-6055","null","null","null","null","null" "Cone beam-computed tomography angiography by intravenous contrast injection is reliable to evaluate patients with large vessel occlusion","Cone beam-computed tomography angiography by intravenous contrast injection is reliable to evaluate patients with large vessel occlusion","Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi, Yasushi Takagi","Nobuaki Yamamoto, Yuki Yamamoto, Izumi Yamaguchi, Manabu Ishihara, Takeshi Miyamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi, Yasushi Takagi","null","Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion (ELVO) is standard treatment, the benefits, however, are highly time-sensitive. After patient eligibility for reperfusion therapy is determined by conventional radiological examinations, the time to be transferred from the department of radiological examination to angiography-suites is critical. We speculated that the time required for the diagnosis of AIS might be reduced if we could determine MT eligibility in patients with ELVO at angiography-suites. Modern angiography-suites with flat panel detectors can perform cone beam (CB)-CT. We performed CB-CTA using intravenous injection of contrast agent to evaluate occlusion sites, collateral score, and construction of vessels distal to occlusion sites and determined if CB-CTA could be useful to evaluate patients with ELVO. We included 15 patients with ELVO diagnosed by conventional MRI or CT/CTA, and investigated whether CB-CTA was reliable to diagnose occlusion sites. We also studied if collateral score on CB-CTA was associated with prognosis after successful reperfusion by MT by comparison between favorable (modified Rankin scale (mRS) 0-2), and unfavorable outcome group (mRS 3-6). There was strong agreement of occlusion sites between CB-CTA and conventional radiological examination (κ = 0.80). Collateral score determined by CB-CTA was significantly different between favorable outcome and unfavorable outcome group (median collateral score 2.3 v.s. 1.3, p = 0.040). Although prospective study of AIS patients at a radiography department is indispensable, CB-CTA performed in an angiography-suite might be useful to evaluate patients with ELVO.","Mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients due to emergent large vessel occlusion (ELVO) is standard treatment, the benefits, however, are highly time-sensitive. After patient eligibility for reperfusion therapy is determined by conventional radiological examinations, the time to be transferred from the department of radiological examination to angiography-suites is critical. We speculated that the time required for the diagnosis of AIS might be reduced if we could determine MT eligibility in patients with ELVO at angiography-suites. Modern angiography-suites with flat panel detectors can perform cone beam (CB)-CT. We performed CB-CTA using intravenous injection of contrast agent to evaluate occlusion sites, collateral score, and construction of vessels distal to occlusion sites and determined if CB-CTA could be useful to evaluate patients with ELVO. We included 15 patients with ELVO diagnosed by conventional MRI or CT/CTA, and investigated whether CB-CTA was reliable to diagnose occlusion sites. We also studied if collateral score on CB-CTA was associated with prognosis after successful reperfusion by MT by comparison between favorable (modified Rankin scale (mRS) 0-2), and unfavorable outcome group (mRS 3-6). There was strong agreement of occlusion sites between CB-CTA and conventional radiological examination (κ = 0.80). Collateral score determined by CB-CTA was significantly different between favorable outcome and unfavorable outcome group (median collateral score 2.3 v.s. 1.3, p = 0.040). Although prospective study of AIS patients at a radiography department is indispensable, CB-CTA performed in an angiography-suite might be useful to evaluate patients with ELVO.","null","null","2019-12","Journal of Clinical Neuroscience","Journal of Clinical Neuroscience","Vol.70","null","67","71","eng","true","null","scientific_journal","null","null","10.1016/j.jocn.2019.08.078","1532-2653","null","null","null","null","null" "メコバラミン","JETALS: The Japanese Early-stage Trial of high dose methylcobalamin for ALS","和泉 唯信, Ryosuke Oki, Satoshi Kuwabara, 梶 龍兒","Yuishin Izumi, Ryosuke Oki, Satoshi Kuwabara, Ryuji Kaji","null","高用量メコバラミンは臨床経験をとおして筋萎縮性側索硬化症(ALS)に対する有効性が示唆され,第Ⅱ/Ⅲ相試験(E0302-J081-761)において部分解析ではあるが発症1年以内のALS患者に対して生存期間延長とALS機能評価スケール(ALSFRS-R)合計点数の低下の抑制効果が認められた.今回われわれは発症1年以内のALS患者に対する高用量メコバラミン(E0302)の有効性・安全性の検証を目的として「高用量E0302の筋萎縮性側索硬化症に対する第Ⅲ相試験—医師主導治験—」(JETALS)を開始した.本治験は前向き,多施設共同,プラセボ対象,二重盲検,ランダム化比較第Ⅲ相試験であり,国内25施設が参加する.128例の被験者に対して16週にわたりE0302 50mgもしくはプラセボの週2回筋肉注射を行う.主要評価項目は割付日から16週目までのALSFRS-R合計点数の変化量である.症例登録期間は2017年11月∼2019年9月であり,2020年3月に治験終了予定である.有効性が確認され早期に承認されることが期待される.","High-dose methylcobalamin was found to be a therapeutic candidate for amyotrophic lateral sclerosis (ALS) through clinical experience. Our previous study (E0302-J081-761) has suggested that high-dose methylcobalamin (E0302) prolonged the overall survival and suppressed progression in ALS patients with a disease duration less than 12 months in, exploratory analyses. Therefore, we plan to conduct an investigator-initiated trial ""The Japan Early-stage Trial of high dose methylcobalamin for ALS (JETALS)"" to evaluate the efficacy and safety of E0302 for ALS patients within 12 months from onset. JETALS is a prospective, multicenter, placebo-controlled, double-blind, randomized Phase III study, conducted at 25 tertiary neurology centers, and is funded by the Japan Agency for Medical Research and Development. A total of 128 patients were randomized at a 1:1 ratio to receive intramuscular injection with E0302 50 mg or placebo, twice a week for 16 weeks. The primary endpoint is changes in the ALS Functional Rating Scale (ALSFRS-R) total score at 16 weeks. The patient enrollment period is from November 2017 to September 2019, and the follow-up is scheduled to end in March 2020. If the results are positive, we intend to apply for E0302 approval for methylcobalamin as a new drug for treating ALS.","null","null","2019-11","脳と神経 - 神経研究の進歩","Brain and Nerve = Shinkei kenkyū no shinpo","Vol.71","No.11","1261","1269","jpn","true","null","scientific_journal","null","null","10.11477/mf.1416201436","1881-6096","null","null","null","null","null" "Co-morbidity of progressive supranuclear palsy and amyotrophic lateral sclerosis: a clinical-pathological case report.","Co-morbidity of progressive supranuclear palsy and amyotrophic lateral sclerosis: a clinical-pathological case report.","Koji Fujita, Tomoyasu Matsubara, Ryosuke Miyamoto, Hiroyuki Sumikura, Toshiaki Takeuchi, Keiko Saladini Maruyama, Toshitaka Kawarai, Hiroyuki Nodera, Fukashi Udaka, Kodai Kume, Hiroyuki Morino, Hideshi Kawakami, Masato Hasegawa, Ryuji Kaji, Shigeo Murayama, Yuishin Izumi","Koji Fujita, Tomoyasu Matsubara, Ryosuke Miyamoto, Hiroyuki Sumikura, Toshiaki Takeuchi, Keiko Saladini Maruyama, Toshitaka Kawarai, Hiroyuki Nodera, Fukashi Udaka, Kodai Kume, Hiroyuki Morino, Hideshi Kawakami, Masato Hasegawa, Ryuji Kaji, Shigeo Murayama, Yuishin Izumi","null","A 77-year-old man presented with gait disturbance for 2 years, consistent with PSP with progressive gait freezing. At 79 years old, he developed muscle weakness compatible with ALS. The disease duration was 5 years after the onset of PSP and 5 months after the onset of ALS. Neuropathological findings demonstrated the coexistence of PSP and ALS. Immunohistochemical examination confirmed 4-repeat tauopathy, including globose-type neurofibrillary tangles, tufted astrocytes, and oligodendroglial coiled bodies as well as TAR DNA-binding protein 43 kDa pathology in association with upper and lower motor neuron degeneration. Immunoblotting showed hyperphosphorylated full-length 4-repeat tau bands (64 and 68 kDa) and C-terminal fragments (33 kDa), supporting the diagnosis of PSP and excluding other parkinsonian disorders, such as corticobasal degeneration. Genetic studies showed no abnormalities in genes currently known to be related to ALS or PSP.","Our case demonstrates the clinicopathological comorbidity of PSP and ALS in a sporadic patient. The possibility of multiple proteinopathies should be considered when distinct symptoms develop during the disease course.","null","null","2019-07-18","BMC Neurology","BMC Neurology","Vol.19","No.1","168","168","eng","true","null","scientific_journal","null","null","10.1186/s12883-019-1402-7","1471-2377","null","null","null","null","null" "A method for differential diagnosis of parkinsonian syndromes","A method for differential diagnosis of parkinsonian syndromes","Wataru Sako, Takashi Abe, Shotaroh Haji, Nagahisa Murakami, Yusuke Osaki, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Shotaroh Haji, Nagahisa Murakami, Yusuke Osaki, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Neurological findings are important for the differential diagnosis of Parkinson's disease (PD), multiple system atrophy with predominant parkinsonian features (MSA-P), and progressive supranuclear palsy (PSP). There is currently no fast and reliable method to distinguish these patients. To address this, we propose a novel approach to measure midbrain and pons size using a longitudinal ""one line"" method from the mid-sagittal view. Structural images were acquired from 101 subjects who underwent 3.0 T MRI (20 controls, 44 PD, 20 MSA, 12 PSP, and 5 corticobasal syndrome). We measured the middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), midbrain, and pons. Brainstem size was measured by area or length of the longitudinal axis, which we named the ""one line"" method. We conducted intraclass correlation coefficients to assess the extent of agreement and consistency among raters, and receiver operating characteristic curves were used to determine diagnostic accuracy. Intraclass correlation coefficients (ICC) of MCP width were excellent in sagittal and axial sections while those of SCP width were moderate. There were also excellent ICCs between raters for ""one line"" method of the midbrain and pons, while areas showed good ICCs. ""One line"" method and area of the midbrain were better than SCP width for the differential diagnosis of PSP from MSA-P and PD. In contrast, there was no clearly superior measurement for differentially diagnosing MSA-P. The ""one line"" method was comparable with area for inter-rater agreement and diagnostic accuracy even though this was a simple and fast way.","Neurological findings are important for the differential diagnosis of Parkinson's disease (PD), multiple system atrophy with predominant parkinsonian features (MSA-P), and progressive supranuclear palsy (PSP). There is currently no fast and reliable method to distinguish these patients. To address this, we propose a novel approach to measure midbrain and pons size using a longitudinal ""one line"" method from the mid-sagittal view. Structural images were acquired from 101 subjects who underwent 3.0 T MRI (20 controls, 44 PD, 20 MSA, 12 PSP, and 5 corticobasal syndrome). We measured the middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), midbrain, and pons. Brainstem size was measured by area or length of the longitudinal axis, which we named the ""one line"" method. We conducted intraclass correlation coefficients to assess the extent of agreement and consistency among raters, and receiver operating characteristic curves were used to determine diagnostic accuracy. Intraclass correlation coefficients (ICC) of MCP width were excellent in sagittal and axial sections while those of SCP width were moderate. There were also excellent ICCs between raters for ""one line"" method of the midbrain and pons, while areas showed good ICCs. ""One line"" method and area of the midbrain were better than SCP width for the differential diagnosis of PSP from MSA-P and PD. In contrast, there was no clearly superior measurement for differentially diagnosing MSA-P. The ""one line"" method was comparable with area for inter-rater agreement and diagnostic accuracy even though this was a simple and fast way.","null","null","2019-06-21","Acta Neurologica Scandinavica","Acta Neurologica Scandinavica","Vol.140","No.3","229","235","eng","true","null","scientific_journal","null","null","10.1111/ane.13136","1600-0404","null","null","null","null","null" "Deterministic-tractography-based approach for diagnosis and disease monitoring of amyotrophic lateral sclerosis","Deterministic-tractography-based approach for diagnosis and disease monitoring of amyotrophic lateral sclerosis","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Upper and lower motor neuron signs are required for the diagnosis of amyotrophic lateral sclerosis. The detection of upper motor neuron signs is key for the diagnosis, as quite a few patients with amyotrophic lateral sclerosis lack upper motor neuron signs during the course of disease. This study sought to investigate whether deterministic tractography of the corticospinal tract, reflecting upper motor neuron signs, could be a surrogate biomarker for amyotrophic lateral sclerosis. Fifteen patients with amyotrophic lateral sclerosis and ten controls underwent imaging on a 3.0 T MRI. The corticospinal tract was reconstructed using deterministic tractography, and the track number was calculated. We analyzed the differences between the groups and the relationship between the track number and disease severity, disease duration, progression rate or upper motor neuron signs. A reduction in the track number of the corticospinal tract was found in amyotrophic lateral sclerosis compared with controls (Student's t test, P = 0.008). The sensitivity and specificity were 0.67 and 0.9, respectively. The track number correlated with disease severity alone (r = 0.71, P = 0.003), and significantly associated with upper motor neuron signs (P = 0.004). These findings suggest that the deterministic-tractography-based approach is a potential biomarker for the diagnosis and disease monitoring of amyotrophic lateral sclerosis.","Upper and lower motor neuron signs are required for the diagnosis of amyotrophic lateral sclerosis. The detection of upper motor neuron signs is key for the diagnosis, as quite a few patients with amyotrophic lateral sclerosis lack upper motor neuron signs during the course of disease. This study sought to investigate whether deterministic tractography of the corticospinal tract, reflecting upper motor neuron signs, could be a surrogate biomarker for amyotrophic lateral sclerosis. Fifteen patients with amyotrophic lateral sclerosis and ten controls underwent imaging on a 3.0 T MRI. The corticospinal tract was reconstructed using deterministic tractography, and the track number was calculated. We analyzed the differences between the groups and the relationship between the track number and disease severity, disease duration, progression rate or upper motor neuron signs. A reduction in the track number of the corticospinal tract was found in amyotrophic lateral sclerosis compared with controls (Student's t test, P = 0.008). The sensitivity and specificity were 0.67 and 0.9, respectively. The track number correlated with disease severity alone (r = 0.71, P = 0.003), and significantly associated with upper motor neuron signs (P = 0.004). These findings suggest that the deterministic-tractography-based approach is a potential biomarker for the diagnosis and disease monitoring of amyotrophic lateral sclerosis.","null","null","2019-04-15","Clinical Neurology and Neurosurgery","Clinical Neurology and Neurosurgery","Vol.181","null","73","75","eng","true","null","scientific_journal","null","null","10.1016/j.clineuro.2019.04.015","1872-6968","null","null","null","null","null" "Potential Utility of 123I-MIBG Scintigraphy as a Predictor of Falls in Parkinson's Disease","Potential Utility of 123I-MIBG Scintigraphy as a Predictor of Falls in Parkinson's Disease","Nagahisa Murakami, Wataru Sako, Shotaroh Haji, Takahiro Furukawa, Yoichi Otomi, Hideki Otsuka, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Nagahisa Murakami, Wataru Sako, Shotaroh Haji, Takahiro Furukawa, Yoichi Otomi, Hideki Otsuka, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Falls are associated with poor prognosis in patients with Parkinson's disease (PD). Although several factors related to falls were reported in patients with PD, objective predictors of falls are not identified. We aimed to determine whether I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy could be a useful biomarker to predict falls. Forty-five patients with PD were enrolled in this study. These subjects were followed up more than 5 years after MIBG scintigraphy and were divided into two groups: one with decreased uptake of MIBG and the other without decreased uptake of MIBG. The cut-off value for the delayed heart-to-mediastinum ratio was 1.8. Kaplan-Meier analysis and a log-rank test were performed to test the predictive power of MIBG cardiac scintigraphy for falls. Univariate analysis was selected because we did not have appropriate data for adjustment, such as motor and cognitive assessment. The group with decreased uptake of MIBG had a significantly higher incidence of falls than that without decreased uptake of MIBG ( = 0.022, log-rank test). Although the limitations of this study were lack of several key factors including motor and cognitive assessment, MIBG cardiac scintigraphy may be used to predict falls in patients with PD.","Falls are associated with poor prognosis in patients with Parkinson's disease (PD). Although several factors related to falls were reported in patients with PD, objective predictors of falls are not identified. We aimed to determine whether I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy could be a useful biomarker to predict falls. Forty-five patients with PD were enrolled in this study. These subjects were followed up more than 5 years after MIBG scintigraphy and were divided into two groups: one with decreased uptake of MIBG and the other without decreased uptake of MIBG. The cut-off value for the delayed heart-to-mediastinum ratio was 1.8. Kaplan-Meier analysis and a log-rank test were performed to test the predictive power of MIBG cardiac scintigraphy for falls. Univariate analysis was selected because we did not have appropriate data for adjustment, such as motor and cognitive assessment. The group with decreased uptake of MIBG had a significantly higher incidence of falls than that without decreased uptake of MIBG ( = 0.022, log-rank test). Although the limitations of this study were lack of several key factors including motor and cognitive assessment, MIBG cardiac scintigraphy may be used to predict falls in patients with PD.","null","null","2019-04-12","Frontiers in Neurology","Frontiers in Neurology","Vol.10","null","376","376","eng","true","null","scientific_journal","null","null","10.3389/fneur.2019.00376","1664-2295","null","null","null","null","null" "The Claw Sign: An angiographic Predictor of Recanalization After Mechanical Thrombectomy for Cerebral Large Vessel Occlusion.","The Claw Sign: An angiographic Predictor of Recanalization After Mechanical Thrombectomy for Cerebral Large Vessel Occlusion.","Yamamoto Yuki, Nobuaki Yamamoto, Yasuhisa Kanematsu, Masaaki Korai, Kenji Shimada, Yuishin Izumi, Yasushi Takagi","Yamamoto Yuki, Nobuaki Yamamoto, Yasuhisa Kanematsu, Masaaki Korai, Kenji Shimada, Yuishin Izumi, Yasushi Takagi","null","Mechanical thrombectomy undoubtedly improves functional outcomes for patients with acute ischemic stroke. Although we have observed occlusion sites that protrude proximally into the vessel on angiography, termed the ""claw sign,"" we have been unable to state its clinical significance. In this study, we aimed to determine whether the presence of a claw sign was related to recanalization success after mechanical thrombectomy. We retrospectively included 73 consecutive patients treated for acute cerebral large vessel occlusion by mechanical thrombectomy between January 2014 and December 2017. The angiographic claw sign was defined as a thrombus that protruded proximally by more than half the diameter of the parent artery. Claw sign positivity, clinical and etiological features, and outcomes were compared between groups with and without recanalization. The claw sign was observed in 29 of 73 (40%) patients and was positive significantly more frequently in those with recanalization (50.0%) than in those without recanalization (5.9%) (P < .01). By multivariate analysis, the claw sign was the only pretreatment parameter to predict successful recanalization (odds ratio, 12.50; 95% confidence interval, 1.50-103.00; P = .019). The presence of the claw sign might predict successful recanalization in patients undergoing mechanical thrombectomy for large vessel occlusion.","Mechanical thrombectomy undoubtedly improves functional outcomes for patients with acute ischemic stroke. Although we have observed occlusion sites that protrude proximally into the vessel on angiography, termed the ""claw sign,"" we have been unable to state its clinical significance. In this study, we aimed to determine whether the presence of a claw sign was related to recanalization success after mechanical thrombectomy. We retrospectively included 73 consecutive patients treated for acute cerebral large vessel occlusion by mechanical thrombectomy between January 2014 and December 2017. The angiographic claw sign was defined as a thrombus that protruded proximally by more than half the diameter of the parent artery. Claw sign positivity, clinical and etiological features, and outcomes were compared between groups with and without recanalization. The claw sign was observed in 29 of 73 (40%) patients and was positive significantly more frequently in those with recanalization (50.0%) than in those without recanalization (5.9%) (P < .01). By multivariate analysis, the claw sign was the only pretreatment parameter to predict successful recanalization (odds ratio, 12.50; 95% confidence interval, 1.50-103.00; P = .019). The presence of the claw sign might predict successful recanalization in patients undergoing mechanical thrombectomy for large vessel occlusion.","null","null","2019-03-28","Journal of Stroke & Cerebrovascular Diseases","Journal of Stroke & Cerebrovascular Diseases","Vol.28","No.6","1555","1560","eng","true","null","scientific_journal","null","null","10.1016/j.jstrokecerebrovasdis.2019.03.007","1532-8511","null","null","null","null","null" "Differences in the intra-cerebellar connections and graph theoretical measures between Parkinson's disease and multiple system atrophy","Differences in the intra-cerebellar connections and graph theoretical measures between Parkinson's disease and multiple system atrophy","Wataru Sako, Takashi Abe, T Furukawa, R Oki, Shotaroh Haji, Nagahisa Murakami, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, T Furukawa, R Oki, Shotaroh Haji, Nagahisa Murakami, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Parkinson's disease (PD) does not present with motor symptoms until dopaminergic neuronal loss exceeds 50%. This might indicate that a network-level compensatory mechanism involving surviving regions in PD acts to reduce brain abnormalities. In contrast, there is no evidence of a compensatory mechanism in multiple system atrophy (MSA). We hypothesized that a comparison of these two diseases would help to identify compensatory effects in PD. We recruited 23 patients with PD, 11 patients with MSA, and 11 controls that showed an aging brain but no neurological deficits. All subjects underwent resting state functional magnetic resonance imaging (fMRI). Regions of interest were defined according to the motor network related to the basal ganglia and cerebellum. Network-level analyses were performed. Network-based statistical analyses revealed that functional connectivity in PD brains was reduced between cerebellar lobules IX on both sides and vermis X, as compared with MSA brains. Transitivity was reduced in MSA as compared with controls. We demonstrated that a part of the intra-cerebellar connectivity was reduced in PD, and that network segregation was reduced in MSA. However, there was no evidence of compensatory effects in PD.","Parkinson's disease (PD) does not present with motor symptoms until dopaminergic neuronal loss exceeds 50%. This might indicate that a network-level compensatory mechanism involving surviving regions in PD acts to reduce brain abnormalities. In contrast, there is no evidence of a compensatory mechanism in multiple system atrophy (MSA). We hypothesized that a comparison of these two diseases would help to identify compensatory effects in PD. We recruited 23 patients with PD, 11 patients with MSA, and 11 controls that showed an aging brain but no neurological deficits. All subjects underwent resting state functional magnetic resonance imaging (fMRI). Regions of interest were defined according to the motor network related to the basal ganglia and cerebellum. Network-level analyses were performed. Network-based statistical analyses revealed that functional connectivity in PD brains was reduced between cerebellar lobules IX on both sides and vermis X, as compared with MSA brains. Transitivity was reduced in MSA as compared with controls. We demonstrated that a part of the intra-cerebellar connectivity was reduced in PD, and that network segregation was reduced in MSA. However, there was no evidence of compensatory effects in PD.","null","null","2019-03-25","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.400","null","129","134","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2019.03.022","1878-5883","null","null","null","null","null" "Deep learning for waveform identification of resting needle electromyography signals","Deep learning for waveform identification of resting needle electromyography signals","Hiroyuki Nodera, Y Osaki, Hiroki Yamazaki, A Mori, Yuishin Izumi, Ryuji Kaji","Hiroyuki Nodera, Y Osaki, Hiroki Yamazaki, A Mori, Yuishin Izumi, Ryuji Kaji","null","Given the recent advent in machine learning and artificial intelligence on medical data analysis, we hypothesized that the deep learning algorithm can classify resting needle electromyography (n-EMG) discharges. Six clinically observed resting n-EMG signals were used as a dataset. The data were converted to Mel-spectrogram. Data augmentation was then applied to the training data. Deep learning algorithms were applied to assess the accuracies of correct classification, with or without the use of pre-trained weights for deep-learning networks. While the original data yielded the accuracy up to 0.86 on the test dataset, data-augmentation up to 200,000 training images showed significant increase in the accuracy to 1.0. The use of pre-trained weights (fine tuning) showed greater accuracy than ""training from scratch"". Resting n-EMG signals were successfully classified by deep-learning algorithm, especially with the use of data augmentation and transfer learning techniques. Computer-aided signal identification of clinical n-EMG testing might be possible by deep-learning algorithms.","Given the recent advent in machine learning and artificial intelligence on medical data analysis, we hypothesized that the deep learning algorithm can classify resting needle electromyography (n-EMG) discharges. Six clinically observed resting n-EMG signals were used as a dataset. The data were converted to Mel-spectrogram. Data augmentation was then applied to the training data. Deep learning algorithms were applied to assess the accuracies of correct classification, with or without the use of pre-trained weights for deep-learning networks. While the original data yielded the accuracy up to 0.86 on the test dataset, data-augmentation up to 200,000 training images showed significant increase in the accuracy to 1.0. The use of pre-trained weights (fine tuning) showed greater accuracy than ""training from scratch"". Resting n-EMG signals were successfully classified by deep-learning algorithm, especially with the use of data augmentation and transfer learning techniques. Computer-aided signal identification of clinical n-EMG testing might be possible by deep-learning algorithms.","null","null","2019-02-23","Clinical Neurophysiology","Clinical Neurophysiology","Vol.130","No.5","617","623","eng","true","null","scientific_journal","null","null","10.1016/j.clinph.2019.01.024","1872-8952","null","null","null","null","null" "MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons","MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons","Fumiko Nakazeki, Itaru Tsuge, Takahiro Horie, Keiko Imamura, Kayoko Tsukita, Akitsu Hotta, Osamu Baba, Yasuhide Kuwabara, Tomohiro Nishino, Tetsushi Nakao, Masataka Nishiga, Hitoo Nishi, Yasuhiro Nakashima, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Shuhei Tsuji, Motoko Naitoh, Shigehiko Suzuki, Yuishin Izumi, Toshitaka Kawarai, Ryuji Kaji, Takeshi Kimura, Haruhisa Inoue, Koh Ono","Fumiko Nakazeki, Itaru Tsuge, Takahiro Horie, Keiko Imamura, Kayoko Tsukita, Akitsu Hotta, Osamu Baba, Yasuhide Kuwabara, Tomohiro Nishino, Tetsushi Nakao, Masataka Nishiga, Hitoo Nishi, Yasuhiro Nakashima, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Shuhei Tsuji, Motoko Naitoh, Shigehiko Suzuki, Yuishin Izumi, Toshitaka Kawarai, Ryuji Kaji, Takeshi Kimura, Haruhisa Inoue, Koh Ono","null","Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here, we show that , which encodes a microtubule-severing protein called SPASTIN, was a novel target gene of in human. Actually, the miR-33 binding site in the 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of on in mice. We demonstrated that inhibition of , a major form of in human neurons, via locked nucleic acid (LNA)-anti-miR ameliorated the pathological phenotype in hereditary spastic paraplegia (HSP)-SPG4 patient induced pluripotent stem cell (iPSC)-derived cortical neurons. Thus, miR-33a can be a potential therapeutic target for the treatment of HSP-SPG4.","Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here, we show that , which encodes a microtubule-severing protein called SPASTIN, was a novel target gene of in human. Actually, the miR-33 binding site in the 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of on in mice. We demonstrated that inhibition of , a major form of in human neurons, via locked nucleic acid (LNA)-anti-miR ameliorated the pathological phenotype in hereditary spastic paraplegia (HSP)-SPG4 patient induced pluripotent stem cell (iPSC)-derived cortical neurons. Thus, miR-33a can be a potential therapeutic target for the treatment of HSP-SPG4.","null","null","2019-02-22","Clinical Science","Clinical Science","Vol.133","No.4","583","595","eng","true","null","scientific_journal","null","null","10.1042/CS20180980","1470-8736","null","null","null","null","null" "Simultaneous approach to tandem occlusion in acute ischemic stroke patients: Percutaneous Transluminal Angioplasty (PTA) using push wire of stent retriever","Simultaneous approach to tandem occlusion in acute ischemic stroke patients: Percutaneous Transluminal Angioplasty (PTA) using push wire of stent retriever","Nobuaki Yamamoto, Yuki Yamamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi, Junichiro Satomi, Yasushi Takagi, Ryuji Kaji","Nobuaki Yamamoto, Yuki Yamamoto, Masaaki Korai, Kenji Shimada, Yasuhisa Kanematsu, Yuishin Izumi, Junichiro Satomi, Yasushi Takagi, Ryuji Kaji","null","null","null","null","null","2019","Journal of Neuroendovascular Therapy","Journal of Neuroendovascular Therapy","Vol.13","No.6","257","261","eng","true","null","scientific_journal","null","null","10.5797/jnet.cr.2018-0108","1882-4072","null","null","null","null","null" "Amyotrophic lateral sclerosis of long clinical course clinically presenting with progressive muscular atrophy","Amyotrophic lateral sclerosis of long clinical course clinically presenting with progressive muscular atrophy","T Matsubara, M Oda, T Takahashi, C Watanabe, Y Tachiyama, H Morino, H Kawakami, Ryuji Kaji, H Maruyama, S Murayama, Yuishin Izumi","T Matsubara, M Oda, T Takahashi, C Watanabe, Y Tachiyama, H Morino, H Kawakami, Ryuji Kaji, H Maruyama, S Murayama, Yuishin Izumi","null","Amyotrophic lateral sclerosis (ALS) primarily affects upper and lower motor neurons. Phosphorylated trans-activation response DNA-binding protein of 43 kDa (TDP-43) inclusion bodies are reportedly a pathological hallmark of sporadic ALS. Here, we present an atypical case of sporadic ALS that progressed very slowly, persisted for 19 years, and clinically appeared to only affect the lower motor neurons; however, upper motor neuron degeneration was detected at autopsy. Furthermore, no inclusion bodies positive for phosphorylated TDP-43, ubiquitin, fused in sarcoma, or superoxide dismutase-1 were detected in the central nervous system. We performed exome-sequencing data analysis but found no genetic disorders. This was therefore an unusual case of lower motor neuron-predominant ALS without TDP-43 pathology or known gene-disease associations. We also reviewed autopsied ALS cases that progressed slowly and had no phosphorylated TDP-43 or ubiquitin-positive inclusions and present the clinicopathological features of such cases. Based on these results, there may be a sporadic ALS subgroup that progresses slowly and shows no accumulation of phosphorylated TDP-43.","Amyotrophic lateral sclerosis (ALS) primarily affects upper and lower motor neurons. Phosphorylated trans-activation response DNA-binding protein of 43 kDa (TDP-43) inclusion bodies are reportedly a pathological hallmark of sporadic ALS. Here, we present an atypical case of sporadic ALS that progressed very slowly, persisted for 19 years, and clinically appeared to only affect the lower motor neurons; however, upper motor neuron degeneration was detected at autopsy. Furthermore, no inclusion bodies positive for phosphorylated TDP-43, ubiquitin, fused in sarcoma, or superoxide dismutase-1 were detected in the central nervous system. We performed exome-sequencing data analysis but found no genetic disorders. This was therefore an unusual case of lower motor neuron-predominant ALS without TDP-43 pathology or known gene-disease associations. We also reviewed autopsied ALS cases that progressed slowly and had no phosphorylated TDP-43 or ubiquitin-positive inclusions and present the clinicopathological features of such cases. Based on these results, there may be a sporadic ALS subgroup that progresses slowly and shows no accumulation of phosphorylated TDP-43.","null","null","2019","Neuropathology","Neuropathology","Vol.39","No.1","47","53","eng","true","null","scientific_journal","null","null","10.1111/neup.12523","1440-1789","null","null","null","null","null" "Texture analysis of sonographic muscle images can distinguish myopathic conditions.","Texture analysis of sonographic muscle images can distinguish myopathic conditions.","Hiroyuki Nodera, Kazuki Sogawa, Naoko Takamatsu, Shuji Hashiguchi, Miho Saito, Atsuko Mori, Yusuke Osaki, Yuishin Izumi, Ryuji Kaji","Hiroyuki Nodera, Kazuki Sogawa, Naoko Takamatsu, Shuji Hashiguchi, Miho Saito, Atsuko Mori, Yusuke Osaki, Yuishin Izumi, Ryuji Kaji","null","Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions. J. Med. Invest. 66 : 237-240, August, 2019.","Given the recent technological advent of muscle ultrasound (US), classification of various myopathic conditions could be possible, especially by mathematical analysis of muscular fine structure called texture analysis. We prospectively enrolled patients with three neuromuscular conditions and their lower leg US images were quantitatively analyzed by texture analysis and machine learning methodology in the following subjects : Inclusion body myositis (IBM) [N=11] ; myotonic dystrophy type 1 (DM1) [N=19] ; polymyositis/dermatomyositis (PM-DM) [N=21]. Although three-group analysis achieved up to 58.8% accuracy, two-group analysis of IBM plus PM-DM versus DM1 showed 78.4% accuracy. Despite the small number of subjects, texture analysis of muscle US followed by machine learning might be expected to be useful in identifying myopathic conditions. J. Med. Invest. 66 : 237-240, August, 2019.","null","null","2019","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.66","No.3,4","237","247","eng","true","null","scientific_journal","null","null","10.2152/jmi.66.237","1349-6867","null","null","null","null","null" "Classification of needle-EMG resting potentials by machine learning","Classification of needle-EMG resting potentials by machine learning","Hiroyuki Nodera, Y Osaki, Hiroki Yamazaki, A Mori, Yuishin Izumi, Ryuji Kaji","Hiroyuki Nodera, Y Osaki, Hiroki Yamazaki, A Mori, Yuishin Izumi, Ryuji Kaji","null","The diagnostic importance of audio signal characteristics in needle electromyography (EMG) is well established. Given the recent advent of audio-sound identification by artificial intelligence, we hypothesized that the extraction of characteristic resting EMG signals and application of machine learning algorithms could help classify various EMG discharges. Data files of 6 classes of resting EMG signals were divided into 2-s segments. Extraction of characteristic features (384 and 4,367 features each) was used to classify the 6 types of discharges using machine learning algorithms. Across 841 audio files, the best overall accuracy of 90.4% was observed for the smaller feature set. Among the feature classes, mel-frequency cepstral coefficients (MFCC)-related features were useful in correct classification. We showed that needle EMG resting signals were satisfactorily classifiable by the combination of feature extraction and machine learning, and this can be applied to clinical settings. Muscle Nerve 59:224-228, 2019.","The diagnostic importance of audio signal characteristics in needle electromyography (EMG) is well established. Given the recent advent of audio-sound identification by artificial intelligence, we hypothesized that the extraction of characteristic resting EMG signals and application of machine learning algorithms could help classify various EMG discharges. Data files of 6 classes of resting EMG signals were divided into 2-s segments. Extraction of characteristic features (384 and 4,367 features each) was used to classify the 6 types of discharges using machine learning algorithms. Across 841 audio files, the best overall accuracy of 90.4% was observed for the smaller feature set. Among the feature classes, mel-frequency cepstral coefficients (MFCC)-related features were useful in correct classification. We showed that needle EMG resting signals were satisfactorily classifiable by the combination of feature extraction and machine learning, and this can be applied to clinical settings. Muscle Nerve 59:224-228, 2019.","null","null","2019","Muscle & Nerve","Muscle & Nerve","Vol.59","No.2","224","229","eng","true","null","scientific_journal","null","null","10.1002/mus.26363","1097-4598","null","null","null","null","null" "Distinct Incidence of Takotsubo Syndrome Between Amyotrophic Lateral Sclerosis and Synucleinopathies: A Cohort Study.","Distinct Incidence of Takotsubo Syndrome Between Amyotrophic Lateral Sclerosis and Synucleinopathies: A Cohort Study.","Yuishin Izumi, Ryosuke Miyamoto, Koji Fujita, Yuki Yamamoto, Hirotsugu Yamada, Tomoyasu Matsubara, Yuki Unai, Ai Tsukamoto, Naoko Takamatsu, Hiroyuki Nodera, Shinya Hayashi, Masaya Oda, Atsuko Mori, Yoshihiko Nishida, Shunsuke Watanabe, Hirohisa Ogawa, Hisanori Uehara, Shigeo Murayama, Masataka Sata, Ryuji Kaji","Yuishin Izumi, Ryosuke Miyamoto, Koji Fujita, Yuki Yamamoto, Hirotsugu Yamada, Tomoyasu Matsubara, Yuki Unai, Ai Tsukamoto, Naoko Takamatsu, Hiroyuki Nodera, Shinya Hayashi, Masaya Oda, Atsuko Mori, Yoshihiko Nishida, Shunsuke Watanabe, Hirohisa Ogawa, Hisanori Uehara, Shigeo Murayama, Masataka Sata, Ryuji Kaji","null","Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory.","Takotsubo syndrome (TTS) is an acute cardiac syndrome characterized by regional left ventricular dysfunction with a peculiar circumferential pattern, which typically results in apical ballooning. Evidence indicates a pivotal role of catecholamines in TTS, and researchers have discussed multiple hypotheses on the etiology, including multivessel coronary spasm, myocardial stunning, excessive transient ventricular afterload, and cardiac sympathetic overactivity with local noradrenaline spillover. Although central nervous system disorders, such as stroke and epilepsy, are known to trigger TTS, the incidence and clinical features of TTS in neurodegenerative disorders are poorly understood. Here, we retrospectively examined TTS cases in a single-center cohort composed of 250 patients with amyotrophic lateral sclerosis (ALS) and 870 patients with synucleinopathies [582 patients with Parkinson's disease (PD), 125 patients with dementia with Lewy bodies (DLB), and 163 patients with multiple system atrophy (MSA)] and identified 4 (1.6%, including 2 women) cases with ALS and no cases with synucleinopathies. Two ALS patients underwent autopsy and the pathological findings were compatible with the chronological changes identified in catecholamine-induced cardiomyopathy. A literature review identified 16 TTS cases with ALS, 1 case each with PD and DLB, and no cases with MSA. When current and previous TTS cases with ALS were concatenated: 55% (11/20) were female; 35% (7/20) had a bulbar-onset and 45% (9/20) had a limb-onset; the mean age of TTS onset was 63.3 ± 9.0 years and the mean interval time from ALS onset to TTS development was 4.9 ± 3.0 years; no (0/16) patients developed TTS within 12 months after ALS onset; 50% (10/20) underwent artificial ventilations; the mortality was 17% (3/18); and most cases had precipitating factors, and TTS development was associated with gastrostomy, tracheostomy, or infections in 45% (9/20) of the patients. This study demonstrated that ALS is a considerable predisposing factor of TTS and that synucleinopathies rarely cause TTS. The distinct TTS incidence between ALS and synucleinopathies may be due to cardiac sympathetic overactivity in ALS and may also be affected by cardiac sympathetic denervation in synucleinopathies. Moreover, the etiology of TTS in ALS may be reasonably explained by the two-hit theory.","null","null","2018-12-13","Frontiers in Neurology","Frontiers in Neurology","Vol.9","null","1099","1099","eng","true","null","scientific_journal","null","null","10.3389/fneur.2018.01099","1664-2295","null","null","null","null","null" "123I-MIBG心筋シンチグラフィーとパーキンソン病患者における転倒リスクの評価","123I-MIBG心筋シンチグラフィーとパーキンソン病患者における転倒リスクの評価","村上 永尚, 佐光 亘, 土師 正太郎, 古川 貴大, 宇山 直人, 音見 暢一, 和泉 唯信, 原田 雅史, 梶 龍兒","村上 永尚, Wataru Sako, 土師 正太郎, Takahiro Furukawa, Naoto Uyama, Youichi Otomi, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","null","null","null","null","2018-12","臨床神経学","Clinical Neurology","Vol.58","No.Suppl.","S213","S213","jpn","true","null","scientific_journal","null","null","null","0009-918X","null","http://search.jamas.or.jp/link/ui/T117590352","null","null","null" "Compound heterozygote mutations in the SIGMAR1 gene in an oldest-old patient with amyotrophic lateral sclerosis.","Compound heterozygote mutations in the SIGMAR1 gene in an oldest-old patient with amyotrophic lateral sclerosis.","Yuishin Izumi, Hiroyuki Morino, Ryosuke Miyamoto, Yukiko Matsuda, Ryosuke Ohsawa, Takashi Kurashige, Yoshimitsu Shimatani, Ryuji Kaji, Hideshi Kawakami","Yuishin Izumi, Hiroyuki Morino, Ryosuke Miyamoto, Yukiko Matsuda, Ryosuke Ohsawa, Takashi Kurashige, Yoshimitsu Shimatani, Ryuji Kaji, Hideshi Kawakami","null","null","null","null","null","2018-10","Geriatrics & Gerontology International","Geriatrics & Gerontology International","Vol.18","No.10","1519","1520","eng","true","null","scientific_journal","null","null","10.1111/ggi.13506","1447-0594","null","null","null","null","null" "CSF cystatin C and diffusion tensor imaging parameters as biomarkers of upper motor neuron degeneration in amyotrophic lateral sclerosis.","CSF cystatin C and diffusion tensor imaging parameters as biomarkers of upper motor neuron degeneration in amyotrophic lateral sclerosis.","Shunya Nakane, Koji Fujita, Shingo Azuma, Ryo Urushihara, Masaki Kamada, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","Shunya Nakane, Koji Fujita, Shingo Azuma, Ryo Urushihara, Masaki Kamada, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","null","MR findings indicated that decreased anisotropy, increased diffusion, and increased myo-inositol/creatine ratio were also significantly correlated with UMN involvement in patients with ALS. The CSF cystatin C levels were significantly lower in patients with ALS than in the other three groups. The reduction of CSF cystatin C levels was significantly correlated with clinical UMN involvement (r = -0.505, p = 0.023).","Reduced cystatin C in CSF can reflect UMN involvement as shown in high-field MR of ALS, potentially providing a new biomarker for UMN degeneration in ALS.","null","null","2018-07-10","Clinical Neurology and Neurosurgery","Clinical Neurology and Neurosurgery","Vol.172","null","162","168","eng","true","null","scientific_journal","null","null","10.1016/j.clineuro.2018.07.008","1872-6968","null","null","null","null","null" "Guillan-Barre syndrome in local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients","Guillan-Barre syndrome in local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients","Naoko Matsui, Hiroyuki Nodera, D Kuzume, N Iwasa, Y Unai, W Sakai, Y Miyazaki, H Yamazaki, Yusuke Osaki, A Mori, T Furukawa, A Tsukamoto-Miyashiro, Y Shimatani, M Yamasaki, Yuishin Izumi, S Kusunoki, Kokichi Arisawa, Ryuji Kaji","Naoko Matsui, Hiroyuki Nodera, D Kuzume, N Iwasa, Y Unai, W Sakai, Y Miyazaki, H Yamazaki, Yusuke Osaki, A Mori, T Furukawa, A Tsukamoto-Miyashiro, Y Shimatani, M Yamasaki, Yuishin Izumi, S Kusunoki, Kokichi Arisawa, Ryuji Kaji","null","Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.","Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.","null","null","2018-05-25","European Journal of Neurology","European Journal of Neurology","Vol.25","No.5","718","724","eng","true","null","scientific_journal","null","null","10.1111/ene.13569","1468-1331","null","null","null","null","null" "未治療のサルコイドーシスに合併した進行性多巣性白質脳症","未治療のサルコイドーシスに合併した進行性多巣性白質脳症","山上 圭, 古川 貴大, 大崎 裕亮, 村上 永尚, 中道 一生, 西條 政幸, 松井 尚子, 和泉 唯信, 梶 龍兒","山上 圭, Takahiro Furukawa, Yusuke Osaki, 村上 永尚, 中道 一生, 西條 政幸, Naoko Matsui, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2018-04-30","神経感染症","Neuroinfection","Vol.23","No.1","151","156","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null" "Phenotype variability and allelic heterogeneity in KMT2B-Associated disease.","Phenotype variability and allelic heterogeneity in KMT2B-Associated disease.","Toshitaka Kawarai, Ryosuke Miyamoto, Eiji Nakagawa, Reiko Koichihara, Takashi Sakamoto, Hideo Mure, Ryoma Morigaki, Hidetaka Koizumi, Ryosuke Oki, Celeste Montecchiani, Carlo Caltagirone, Antonio Orlacchio, Ayako Hattori, Hideaki Mashimo, Yuishin Izumi, Takahiro Mezaki, Satoko Kumada, Makoto Taniguchi, Fusako Yokochi, Shinji Saitoh, Satoshi Goto, Ryuji Kaji","Toshitaka Kawarai, Ryosuke Miyamoto, Eiji Nakagawa, Reiko Koichihara, Takashi Sakamoto, Hideo Mure, Ryoma Morigaki, Hidetaka Koizumi, Ryosuke Oki, Celeste Montecchiani, Carlo Caltagirone, Antonio Orlacchio, Ayako Hattori, Hideaki Mashimo, Yuishin Izumi, Takahiro Mezaki, Satoko Kumada, Makoto Taniguchi, Fusako Yokochi, Shinji Saitoh, Satoshi Goto, Ryuji Kaji","null","We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.","We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.","null","null","2018-04-05","Parkinsonism & Related Disorders","Parkinsonism & Related Disorders","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1016/j.parkreldis.2018.03.022","1873-5126","null","null","null","null","null" "Risk Factors of Neurological Deterioration in Patients with Cerebral Infarction due to Large Artery Atherosclerosis","Risk Factors of Neurological Deterioration in Patients with Cerebral Infarction due to Large Artery Atherosclerosis","Nobuaki Yamamoto, Junichiro Satomi, Yuki Yamamoto, Kenji Shono, Yasuhisa Kanematsu, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Junichiro Satomi, Yuki Yamamoto, Kenji Shono, Yasuhisa Kanematsu, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","null","In some patients with acute ischemic stroke, neurological deterioration (ND) is observed, and it is difficult to predict at the time of admission. Especially in some patients with large-artery atherosclerosis (LAA), aggressive medical treatments and surgical interventions might be helpful to prevent ND. Therefore, we investigated factors associated with ND in patients with LAA. We studied patients with LAA who were admitted to our hospital. We divided them into 2 groups with (group 1) and without deterioration (group 2), and evaluated their medical records, risk factors, and radiological findings, such as number of diffusion-positive lesion and degree of stenosis. Our study population consisted of 171 patients; 71 (41.5%) did and 100 (58.5%) did not suffer deterioration. By univariate analysis, blood pressure (BP), heart rate, National Institutes of Health Stroke Scale (NIHSS) score, number of diffusion-positive lesion, count of red blood cell, high-density lipoprotein, and degree of stenosis differed significantly between the 2 groups. By multivariate analysis, systolic BP (170 mm Hg, odds ratio: 7.20, P <.001) was associated with ND. Furthermore, number of diffusion-weighted image (DWI)-positive lesion (8), degree of stenosis (>80.0%), and NIHSS score (4) were also independent factors associated with ND. High BP, severity of neurological deficit at the time of admission, and radiological findings, such as degree of stenosis and number of DWI-positive lesion, are independently associated with ND in patients with LAA.","In some patients with acute ischemic stroke, neurological deterioration (ND) is observed, and it is difficult to predict at the time of admission. Especially in some patients with large-artery atherosclerosis (LAA), aggressive medical treatments and surgical interventions might be helpful to prevent ND. Therefore, we investigated factors associated with ND in patients with LAA. We studied patients with LAA who were admitted to our hospital. We divided them into 2 groups with (group 1) and without deterioration (group 2), and evaluated their medical records, risk factors, and radiological findings, such as number of diffusion-positive lesion and degree of stenosis. Our study population consisted of 171 patients; 71 (41.5%) did and 100 (58.5%) did not suffer deterioration. By univariate analysis, blood pressure (BP), heart rate, National Institutes of Health Stroke Scale (NIHSS) score, number of diffusion-positive lesion, count of red blood cell, high-density lipoprotein, and degree of stenosis differed significantly between the 2 groups. By multivariate analysis, systolic BP (170 mm Hg, odds ratio: 7.20, P <.001) was associated with ND. Furthermore, number of diffusion-weighted image (DWI)-positive lesion (8), degree of stenosis (>80.0%), and NIHSS score (4) were also independent factors associated with ND. High BP, severity of neurological deficit at the time of admission, and radiological findings, such as degree of stenosis and number of DWI-positive lesion, are independently associated with ND in patients with LAA.","null","null","2017-08","Journal of Stroke & Cerebrovascular Diseases","Journal of Stroke & Cerebrovascular Diseases","Vol.26","No.8","1801","1806","eng","true","null","scientific_journal","null","null","10.1016/j.jstrokecerebrovasdis.2017.04.011","1532-8511","null","null","null","null","null" "Spastic paraplegia type 4: A novel SPAST splice site donor mutation and expansion of the phenotype variability.","Spastic paraplegia type 4: A novel SPAST splice site donor mutation and expansion of the phenotype variability.","Toshitaka Kawarai, Celeste Montecchiani, Ryosuke Miyamoto, Fabrizio Gaudiello, Carlo Caltagirone, Yuishin Izumi, Ryuji Kaji, Antonio Orlacchio","Toshitaka Kawarai, Celeste Montecchiani, Ryosuke Miyamoto, Fabrizio Gaudiello, Carlo Caltagirone, Yuishin Izumi, Ryuji Kaji, Antonio Orlacchio","null","Mutations in SPG4/SPAST are the most frequent molecular aetiology in the autosomal dominant form of hereditary spastic paraplegia (HSP). Loss-of-function and haploinsufficiency in SPAST have been demonstrated and the pure form of spastic paraplegia is a main clinical manifestation. This study is to explore the novel SPAST splice site donor variant, c.1004+3A>C, in seven patients from two families, one from Italy and the other from Japan. Exon 6 is skipped out by the variant, leading to a premature termination of translation, p.Gly290Trpfs*5. Measurement of SPAST transcripts in lymphocytes demonstrated a reduction through nonsense-mediated mRNA decay (NMD). Intra- and inter-familial phenotypic variations were observed, including age-at-onset, severity of spasticity, and scoliosis. Our study demonstrated further evidence of allelic heterogeneity in SPG4, dosage effects through NMD, and broad clinical features of the SPAST mutation.","Mutations in SPG4/SPAST are the most frequent molecular aetiology in the autosomal dominant form of hereditary spastic paraplegia (HSP). Loss-of-function and haploinsufficiency in SPAST have been demonstrated and the pure form of spastic paraplegia is a main clinical manifestation. This study is to explore the novel SPAST splice site donor variant, c.1004+3A>C, in seven patients from two families, one from Italy and the other from Japan. Exon 6 is skipped out by the variant, leading to a premature termination of translation, p.Gly290Trpfs*5. Measurement of SPAST transcripts in lymphocytes demonstrated a reduction through nonsense-mediated mRNA decay (NMD). Intra- and inter-familial phenotypic variations were observed, including age-at-onset, severity of spasticity, and scoliosis. Our study demonstrated further evidence of allelic heterogeneity in SPG4, dosage effects through NMD, and broad clinical features of the SPAST mutation.","null","null","2017-07-09","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.380","null","92","97","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2017.07.011","1878-5883","null","null","null","null","null" "Usefulness of the superior cerebellar peduncle for differential diagnosis of progressive supranuclear palsy: A meta-analysis.","Usefulness of the superior cerebellar peduncle for differential diagnosis of progressive supranuclear palsy: A meta-analysis.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","Previous studies have reported the usefulness of superior cerebellar peduncle (SCP) abnormalities in diagnosing progressive supranuclear palsy. However, the results of these studies were heterogeneous. In the present meta-analysis, we aimed to establish more robust evidence of SCP abnormalities in progressive supranuclear palsy, and to determine the cause of the previously reported heterogeneity. We identified six studies on SCP size and three studies on apparent diffusion coefficient. Key features of each study were extracted and standardized differences in size and apparent diffusion coefficient values were calculated. There was some heterogeneity in terms of the reduction in SCP size in patients with progressive supranuclear palsy compared to those with Parkinson's disease. Moreover, age and Hoehn-Yahr stage negatively correlated with standardized mean difference in SCP size between patients with progressive supranuclear palsy and Parkinson's disease. There was homogenous agreement that the SCP was smaller in patients with progressive supranuclear palsy compared to those with multiple system atrophy. Finally, in terms of apparent diffusion coefficient, there was no significant difference between patients with progressive supranuclear palsy, Parkinson's disease, or multiple system atrophy. Together, these findings suggest that SCP size, when corrected for age and disease severity, could be a diagnostic tool for progressive supranuclear palsy.","Previous studies have reported the usefulness of superior cerebellar peduncle (SCP) abnormalities in diagnosing progressive supranuclear palsy. However, the results of these studies were heterogeneous. In the present meta-analysis, we aimed to establish more robust evidence of SCP abnormalities in progressive supranuclear palsy, and to determine the cause of the previously reported heterogeneity. We identified six studies on SCP size and three studies on apparent diffusion coefficient. Key features of each study were extracted and standardized differences in size and apparent diffusion coefficient values were calculated. There was some heterogeneity in terms of the reduction in SCP size in patients with progressive supranuclear palsy compared to those with Parkinson's disease. Moreover, age and Hoehn-Yahr stage negatively correlated with standardized mean difference in SCP size between patients with progressive supranuclear palsy and Parkinson's disease. There was homogenous agreement that the SCP was smaller in patients with progressive supranuclear palsy compared to those with multiple system atrophy. Finally, in terms of apparent diffusion coefficient, there was no significant difference between patients with progressive supranuclear palsy, Parkinson's disease, or multiple system atrophy. Together, these findings suggest that SCP size, when corrected for age and disease severity, could be a diagnostic tool for progressive supranuclear palsy.","null","null","2017-05-03","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.378","null","153","157","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2017.05.005","1878-5883","null","null","null","null","null" "Proteasome impairment in neural cells derived from HMSN-P patient iPSCs.","Proteasome impairment in neural cells derived from HMSN-P patient iPSCs.","Nagahisa Murakami, Keiko Imamura, Yuishin Izumi, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Takuya Yamamoto, Toshitaka Kawarai, Ryuji Kaji, Haruhisa Inoue","Nagahisa Murakami, Keiko Imamura, Yuishin Izumi, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Takuya Yamamoto, Toshitaka Kawarai, Ryuji Kaji, Haruhisa Inoue","null","Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration. Here we generated induced pluripotent stem cells (iPSCs) from HMSN-P patients, and differentiated the iPSCs into neural cells with spinal motor neurons (iPS-MNs). We found that HMSN-P patient iPS-MNs exhibited ubiquitin proteasome system (UPS) impairment, and HMSN-P patient iPS-MNs were vulnerable to UPS inhibitory stress. Gene correction of the mutation in TFG using the CRISPR-Cas9 system reverted the cellular phenotypes of HMSN-P patient iPS-MNs. Collectively, these results suggest that our cellular model with defects in cellular integrity including UPS impairments may lead to identification of pathomechanisms and a therapeutic target for HMSN-P.","Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration. Here we generated induced pluripotent stem cells (iPSCs) from HMSN-P patients, and differentiated the iPSCs into neural cells with spinal motor neurons (iPS-MNs). We found that HMSN-P patient iPS-MNs exhibited ubiquitin proteasome system (UPS) impairment, and HMSN-P patient iPS-MNs were vulnerable to UPS inhibitory stress. Gene correction of the mutation in TFG using the CRISPR-Cas9 system reverted the cellular phenotypes of HMSN-P patient iPS-MNs. Collectively, these results suggest that our cellular model with defects in cellular integrity including UPS impairments may lead to identification of pathomechanisms and a therapeutic target for HMSN-P.","null","null","2017-02-15","Molecular Brain","Molecular Brain","Vol.10","No.1","null","null","eng","true","null","scientific_journal","null","null","10.1186/s13041-017-0286-y","1756-6606","null","null","null","null","null" "Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity.","Spontaneous brain activity in the sensorimotor cortex in amyotrophic lateral sclerosis can be negatively regulated by corticospinal fiber integrity.","Wataru Sako, Takashi Abe, Yuishin Izumi, Hiroki Yamazaki, Naoko Matsui, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Yuishin Izumi, Hiroki Yamazaki, Naoko Matsui, Masafumi Harada, Ryuji Kaji","null","Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.","Previous studies failed to detect reduced value of the amplitude of low frequency fluctuation (ALFF) derived from resting state functional magnetic resonance imaging in the primary motor cortex in amyotrophic lateral sclerosis (ALS) though primary motor cortex was mainly affected with ALS. We aimed to investigate the cause of masking the abnormality in the primary motor cortex in ALS and usefulness of ALFF for differential diagnosis among diseases showing muscle weakness. We enrolled ten patients with ALS and eleven disease controls showing muscle weakness. Voxel-wise analysis revealed that significant reduction of ALFF value was present in the right sensorimotor cortex in ALS. There was a significant negative correlation between ALFF value in the right sensorimotor cortex and fractional anisotropy (FA) value in the posterior limbs of the internal capsule (PLIC). For a diagnostic tool, the area under receiver operating characteristic curve improved if the ALS patients with disease duration >1 year were excluded. The present findings raised the possibility of usefulness of ALFF value in the sensorimotor cortex for differential diagnosis of ALS, and supported the notion that adjustment for FA value in the PLIC could improve accuracy.","null","null","2017-02-01","Neurological Sciences","Neurological Sciences","Vol.38","No.5","755","760","eng","true","null","scientific_journal","null","null","10.1007/s10072-017-2831-y","1590-3478","null","null","null","null","null" "シャルコー・マリー・トウース病に類似した三頭酵素欠損症の成人例","Mitochondrial trifunctional protein deficiency: an adult patient with similar progress to Charcot-Marie-Tooth disease.","山本 雄貴, 松井 尚子, 平松 有, 宮﨑 由道, 野寺 裕之, 和泉 唯信, 高嶋 博, 梶 龍兒","Yuki Yamamoto, Naoko Matsui, 平松 有, Yoshimichi Miyazaki, Hiroyuki Nodera, Yuishin Izumi, 高嶋 博, Ryuji Kaji","null","A 45-year-old man presented to us due to slowly progressive muscle weakness and sensory disturbances in his lower limbs since his 40's. He reported multiple episodes of exercise-induced severe muscle fatigue and brown urine in his childhood, which disappeared by age 20. A nerve conduction study showed peripheral axonal neuropathy and then Charcot-Marie-Tooth disease (CMT) was considered as the most likely diagnosis; however, exome sequencing failed to identify a mutation in the known genes of CMTs. Since age 55, he recurrently developed severe rhabdomyolysis that required hospitalization. On suspicion of lipid metabolism disorders, we performed serum acylcarnitine analysis, and which revealed mildly elevated long-chain fatty acids. We re-examined variants obtained via exome sequencing and found a mutation in HADHB. Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid beta-oxidation caused by HADHA or HADHB mutation. It can be a life-threatening multiorgan disorder with early infantile onset, but it can also present in childhood or adolescence with peripheral neuropathy and recurrent rhabdomyolysis. This case of adult-diagnosed MTP deficiency was characterized by slowly progressive peripheral neuropathy masquerading CMT in addition to muscular symptoms. MTP deficiency should be considered in patients with the combination of peripheral neuropathy and recurrent rhabdomyolysis.","A 45-year-old man presented to us due to slowly progressive muscle weakness and sensory disturbances in his lower limbs since his 40's. He reported multiple episodes of exercise-induced severe muscle fatigue and brown urine in his childhood, which disappeared by age 20. A nerve conduction study showed peripheral axonal neuropathy and then Charcot-Marie-Tooth disease (CMT) was considered as the most likely diagnosis; however, exome sequencing failed to identify a mutation in the known genes of CMTs. Since age 55, he recurrently developed severe rhabdomyolysis that required hospitalization. On suspicion of lipid metabolism disorders, we performed serum acylcarnitine analysis, and which revealed mildly elevated long-chain fatty acids. We re-examined variants obtained via exome sequencing and found a mutation in HADHB. Mitochondrial trifunctional protein (MTP) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid beta-oxidation caused by HADHA or HADHB mutation. It can be a life-threatening multiorgan disorder with early infantile onset, but it can also present in childhood or adolescence with peripheral neuropathy and recurrent rhabdomyolysis. This case of adult-diagnosed MTP deficiency was characterized by slowly progressive peripheral neuropathy masquerading CMT in addition to muscular symptoms. MTP deficiency should be considered in patients with the combination of peripheral neuropathy and recurrent rhabdomyolysis.","null","null","2017-02","臨床神経学","Clinical Neurology","Vol.57","No.2","82","87","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.cn-000976","1882-0654","null","null","null","null","null" "耳下腺炎を契機に発症し,脳病変のみを反復したシェーグレン症候群合併視神経脊髄炎関連疾患の一例","A case of neuromyelitis optica spectrum disorder (NMOSD) with Sjögren's syndrome manifested only brain involvement by preceding parotitis.","古川 貴大, 松井 尚子, 田中 惠子, 和泉 唯信, 梶 龍兒","Takahiro Furukawa, Naoko Matsui, 田中 惠子, Yuishin Izumi, Ryuji Kaji","null","A 33 year-old woman presented with intentional incontinence, motor aphasia, supranuclear gaze palsy, and spasticity after parotitis. Brain magnetic resonance images (MRI) showed abnormal signaling in long corticospinal tract involving internal capsules and cerebral peduncles, middle cerebellar peduncle, and frontal subcortical white matter lesions. She had a long history of dry eye and mouth. Immunoserological study showed that she was positive for anti-SS-A, aquaporin 4 (AQP4), and AQP5 antibodies. She clinically showed not only Sjögren's syndrome but also neuromyelitis optica spectrum disorder (NMOSD) without optic neuritis or myelitis. She responded to steroid followed by plasma exchange dramatically. Thereafter, the relapse of brain lesion was once detected while tapering of steroid, but her symptoms have been stable for several years after administration of immunosuppressant. This case suggested that salivary gland inflammation might be associated with the pathogenesis of NMOSD.","A 33 year-old woman presented with intentional incontinence, motor aphasia, supranuclear gaze palsy, and spasticity after parotitis. Brain magnetic resonance images (MRI) showed abnormal signaling in long corticospinal tract involving internal capsules and cerebral peduncles, middle cerebellar peduncle, and frontal subcortical white matter lesions. She had a long history of dry eye and mouth. Immunoserological study showed that she was positive for anti-SS-A, aquaporin 4 (AQP4), and AQP5 antibodies. She clinically showed not only Sjögren's syndrome but also neuromyelitis optica spectrum disorder (NMOSD) without optic neuritis or myelitis. She responded to steroid followed by plasma exchange dramatically. Thereafter, the relapse of brain lesion was once detected while tapering of steroid, but her symptoms have been stable for several years after administration of immunosuppressant. This case suggested that salivary gland inflammation might be associated with the pathogenesis of NMOSD.","null","null","2017-02","臨床神経学","Clinical Neurology","Vol.57","No.2","77","81","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.cn-000924","1882-0654","null","null","null","null","null" "Optimal Timing of Diffusion-Weighted Imaging to Avoid False-Negative Findings in Patients With Transient Ischemic Attack","Optimal Timing of Diffusion-Weighted Imaging to Avoid False-Negative Findings in Patients With Transient Ischemic Attack","Kenji Shono, Junichiro Satomi, Yoshiteru Tada, Yasuhisa Kanematsu, Nobuaki Yamamoto, Yuishin Izumi, Ryuji Kaji, Masafumi Harada, Shinji Nagahiro","Kenji Shono, Junichiro Satomi, Yoshiteru Tada, Yasuhisa Kanematsu, Nobuaki Yamamoto, Yuishin Izumi, Ryuji Kaji, Masafumi Harada, Shinji Nagahiro","null","We aimed to investigate the optimal timing of diffusion-weighted imaging (DWI) in patients with transient ischemic attack (TIA). Seventy-three consecutive patients with TIA underwent DWI on admission (initial DWI) and at 24 hours after admission (second DWI). Patients were divided into 2 groups based on initial DWI findings in relation to the second examination: false negative (group 1) and other (group 2). The probability of initial false-negative findings was determined for each hour from TIA onset to initial DWI. Multivariate analysis was used to evaluate the independent risk factors associated with false-negative findings on initial DWI. Of the 73 patients examined (56 men; mean age, 68 years), 9 (12%) were categorized into group 1. The latency from TIA onset to initial DWI was 1.7±0.6 hours for group 1 (range, 1-2.8 hours) and 3.3±2.6 hours for group 2 (range, 35 minutes to 12 hours). The probability of false-negative findings on initial DWI decreased in a time-dependent manner (25%, 21%, and 7% for 1, 2, and 3 hours, respectively), and no false-negative findings were observed on initial DWI performed at >3 hours from symptom onset. Short latency (2 hours) from TIA onset to initial DWI was an independent risk factor related to false-negative findings (odds ratio, 13.11; 95% confidence interval, 1.07-161.38; P=0.045). If the duration between TIA symptom onset and initial DWI is <2 hours, a repeat examination should be performed to minimize the risk of false-positive findings.","We aimed to investigate the optimal timing of diffusion-weighted imaging (DWI) in patients with transient ischemic attack (TIA). Seventy-three consecutive patients with TIA underwent DWI on admission (initial DWI) and at 24 hours after admission (second DWI). Patients were divided into 2 groups based on initial DWI findings in relation to the second examination: false negative (group 1) and other (group 2). The probability of initial false-negative findings was determined for each hour from TIA onset to initial DWI. Multivariate analysis was used to evaluate the independent risk factors associated with false-negative findings on initial DWI. Of the 73 patients examined (56 men; mean age, 68 years), 9 (12%) were categorized into group 1. The latency from TIA onset to initial DWI was 1.7±0.6 hours for group 1 (range, 1-2.8 hours) and 3.3±2.6 hours for group 2 (range, 35 minutes to 12 hours). The probability of false-negative findings on initial DWI decreased in a time-dependent manner (25%, 21%, and 7% for 1, 2, and 3 hours, respectively), and no false-negative findings were observed on initial DWI performed at >3 hours from symptom onset. Short latency (2 hours) from TIA onset to initial DWI was an independent risk factor related to false-negative findings (odds ratio, 13.11; 95% confidence interval, 1.07-161.38; P=0.045). If the duration between TIA symptom onset and initial DWI is <2 hours, a repeat examination should be performed to minimize the risk of false-positive findings.","null","null","2017-01","Stroke","Stroke","Vol.48","No.7","1990","1992","eng","true","null","scientific_journal","null","null","10.1161/STROKEAHA.117.014576","1524-4628","null","null","null","null","null" "複合的免疫治療が奏功した抗SRP抗体陽性壊死性ミオパチーの1例","A Case of Anti-SRP Positive Immune-mediated Necrotizing Myopathy Treated Effectively with Combined Immunotherapy","山下 雄也, 山崎 博輝, 松井 尚子, 宮﨑 由道, 塚本 愛, 西野 一三, 鈴木 重明, 西田 善彦, 野寺 裕之, 和泉 唯信, 梶 龍兒","山下 雄也, Hiroki Yamazaki, Naoko Matsui, Yoshimichi Miyazaki, 塚本 愛, 西野 一三, 鈴木 重明, 西田 善彦, Hiroyuki Nodera, Yuishin Izumi, Ryuji Kaji","null","症例は60歳代,男性.全身倦怠感,四肢脱力を主訴に受診.筋炎としステロイド単独で治療を開始したが,反応性は乏しく,筋病理・抗体検査にて抗SRP抗体陽性壊死性ミオパチー(anti-signal recognition particle immune-mediated necrotizing myopathy:anti-SRP iNM)と診断し,免疫グロブリン大量静注療法,免疫抑制薬を併用したところ,症状の改善を得た.積極的に自己抗体の測定を行うことが壊死性ミオパチー(immune-mediated necrotizing myopathy:iNM)の早期診断・治療に重要である.
","症例は60歳代,男性.全身倦怠感,四肢脱力を主訴に受診.筋炎としステロイド単独で治療を開始したが,反応性は乏しく,筋病理・抗体検査にて抗SRP抗体陽性壊死性ミオパチー(anti-signal recognition particle immune-mediated necrotizing myopathy:anti-SRP iNM)と診断し,免疫グロブリン大量静注療法,免疫抑制薬を併用したところ,症状の改善を得た.積極的に自己抗体の測定を行うことが壊死性ミオパチー(immune-mediated necrotizing myopathy:iNM)の早期診断・治療に重要である.
","null","null","2016-08","日本内科学会雑誌","The Journal of the Japanese Society of Internal Medicine","Vol.105","No.8","1443","1450","jpn","true","null","scientific_journal","null","null","10.2169/naika.105.1443","1883-2083","null","http://ci.nii.ac.jp/naid/130005950164/","null","null","null" "Imaging-based differential diagnosis between multiple system atrophy and Parkinson's disease.","Imaging-based differential diagnosis between multiple system atrophy and Parkinson's disease.","Wataru Sako, Takashi Abe, Nagahisa Murakami, Yoshimichi Miyazaki, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Nagahisa Murakami, Yoshimichi Miyazaki, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","There are many tools for differentiating between multiple system atrophy with predominant parkinsonian features (MSA-P) and Parkinson's disease (PD). These include middle cerebellar peduncle (MCP) width, apparent diffusion coefficient (ADC) value of the putamen and cerebellum, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy images. We aimed to directly compare the above-mentioned methods, and to determine the optimal tool for differential diagnosis. Eleven patients with MSA-P and 36 patients with PD were enrolled. Of these, 7 patients with MSA-P and 14 patients with PD were chosen as background-matched subjects. We measured MCP width, ADC value of the putamen and cerebellum, and MIBG myocardial scintigraphy images. Area under curve (AUC) of receiver operating characteristic (ROC) was assessed to compare the above-mentioned methods. MCP width and ADC value of the putamen may be helpful for differentiating between MSA-P and PD relative to other methods in background-matched patients (MCP, AUC=0.95; putamen ADC, AUC=0.88; cerebellar ADC, AUC=0.70; MIBG, AUC=0.78). Similar AUCs were seen in all patients with different backgrounds. Our findings suggested that MCP width and ADC value of the putamen could be superior to ADC value of the cerebellum and MIBG uptake for differentiating between MSA-P and PD.","There are many tools for differentiating between multiple system atrophy with predominant parkinsonian features (MSA-P) and Parkinson's disease (PD). These include middle cerebellar peduncle (MCP) width, apparent diffusion coefficient (ADC) value of the putamen and cerebellum, and (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy images. We aimed to directly compare the above-mentioned methods, and to determine the optimal tool for differential diagnosis. Eleven patients with MSA-P and 36 patients with PD were enrolled. Of these, 7 patients with MSA-P and 14 patients with PD were chosen as background-matched subjects. We measured MCP width, ADC value of the putamen and cerebellum, and MIBG myocardial scintigraphy images. Area under curve (AUC) of receiver operating characteristic (ROC) was assessed to compare the above-mentioned methods. MCP width and ADC value of the putamen may be helpful for differentiating between MSA-P and PD relative to other methods in background-matched patients (MCP, AUC=0.95; putamen ADC, AUC=0.88; cerebellar ADC, AUC=0.70; MIBG, AUC=0.78). Similar AUCs were seen in all patients with different backgrounds. Our findings suggested that MCP width and ADC value of the putamen could be superior to ADC value of the cerebellum and MIBG uptake for differentiating between MSA-P and PD.","null","null","2016-06-29","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.368","null","104","108","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2016.06.061","1878-5883","null","null","null","null","null" "Mystery Case: Parkinsonism in a diabetic uremic patient.","Mystery Case: Parkinsonism in a diabetic uremic patient.","Yusuke Osaki, Koji Fujita, Takashi Abe, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","Yusuke Osaki, Koji Fujita, Takashi Abe, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2016-06-01","Neurology","Neurology","Vol.86","No.22","e225","7","eng","true","null","scientific_journal","null","null","10.1212/WNL.0000000000002713","1526-632X","null","null","null","null","null" "MFN2 transcripts escaping from nonsense-mediated mRNA decay pathway cause Charcot-Marie-Tooth disease type 2A2","MFN2 transcripts escaping from nonsense-mediated mRNA decay pathway cause Charcot-Marie-Tooth disease type 2A2","Toshitaka Kawarai, Kanto Yamasaki, Atsuko Mori, Naoko Takamatsu, Yusuke Osaki, Chimeglkham Banzrai, Chimeglkham Banzrai, Ryosuke Miyamoto, Ryosuke Oki, Lucia Pedace, Antonio Orlacchio, Hiroyuki Nodera, Akihiro Hashiguchi, Yujiro Higuchi, Hiroshi Takashima, Yoshihiko Nishida, Yuishin Izumi, Ryuji Kaji","Toshitaka Kawarai, Kanto Yamasaki, Atsuko Mori, Naoko Takamatsu, Yusuke Osaki, Chimeglkham Banzrai, Chimeglkham Banzrai, Ryosuke Miyamoto, Ryosuke Oki, Lucia Pedace, Antonio Orlacchio, Hiroyuki Nodera, Akihiro Hashiguchi, Yujiro Higuchi, Hiroshi Takashima, Yoshihiko Nishida, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2016-06","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2015-312646","1468-330X","null","null","null","null","null" "Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis","Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis","Kaji Seiji, Toshitaka Kawarai, Miyamoto Ryosuke, Hiroyuki Nodera, Pedace Lucia, Orlacchio Antonio, Yuishin Izumi, Takahashi Ryosuke, Ryuji Kaji","Kaji Seiji, Toshitaka Kawarai, Miyamoto Ryosuke, Hiroyuki Nodera, Pedace Lucia, Orlacchio Antonio, Yuishin Izumi, Takahashi Ryosuke, Ryuji Kaji","null","Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS.","Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS.","null","null","2016-03-02","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.364","null","45","49","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2016.03.001","1878-5883","null","null","null","null","null" "The difference of apparent diffusion coefficient in the middle cerebellar peduncle among parkinsonian syndromes: Evidence from a meta-analysis.","The difference of apparent diffusion coefficient in the middle cerebellar peduncle among parkinsonian syndromes: Evidence from a meta-analysis.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","The measurement of middle cerebellar peduncle (MCP) width allows for differential diagnosis between Parkinson's disease (PD) and multiple system atrophy with predominant parkinsonian features (MSA-P). However, it remains controversial whether apparent diffusion coefficient (ADC) value in the MCP of MSA-P is elevated or not. In the present study, we aimed to assess the usefulness of ADC value in the MCP for differential diagnosis between PD and MSA-P. An on-line literature search yielded 5 eligible studies. We expressed between-group difference of ADC value as the standardized mean difference (SMD). The proportion of variation due to heterogeneity was computed and expressed as I(2). ADC in the MCP of MSA-P was significantly increased compared with PD with heterogeneous studies (P=0.0007, I(2)=81%). A meta-regression analysis of MSA-P was conducted for ""UPDRS III"", and revealed a significant correlation between UPDRS III and SMD (P=0.01). Our meta-regression analysis has clarified the contribution of severity of MSA-P to heterogeneity of the included studies for ADC in the MCP. This finding raised the possibility that ADC in the MCP depended on severity of MSA-P, and less severe patients with MSA-P should be mainly enrolled in future study to assess the ability for differential diagnostic tool.","The measurement of middle cerebellar peduncle (MCP) width allows for differential diagnosis between Parkinson's disease (PD) and multiple system atrophy with predominant parkinsonian features (MSA-P). However, it remains controversial whether apparent diffusion coefficient (ADC) value in the MCP of MSA-P is elevated or not. In the present study, we aimed to assess the usefulness of ADC value in the MCP for differential diagnosis between PD and MSA-P. An on-line literature search yielded 5 eligible studies. We expressed between-group difference of ADC value as the standardized mean difference (SMD). The proportion of variation due to heterogeneity was computed and expressed as I(2). ADC in the MCP of MSA-P was significantly increased compared with PD with heterogeneous studies (P=0.0007, I(2)=81%). A meta-regression analysis of MSA-P was conducted for ""UPDRS III"", and revealed a significant correlation between UPDRS III and SMD (P=0.01). Our meta-regression analysis has clarified the contribution of severity of MSA-P to heterogeneity of the included studies for ADC in the MCP. This finding raised the possibility that ADC in the MCP depended on severity of MSA-P, and less severe patients with MSA-P should be mainly enrolled in future study to assess the ability for differential diagnostic tool.","null","null","2016-02-16","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.363","null","90","94","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2016.02.034","1878-5883","null","null","null","null","null" "Late-onset myasthenia gravis is predisposed to become generalized in the elderly","Late-onset myasthenia gravis is predisposed to become generalized in the elderly","Waka Sakai, Naoko Matsui, Mitsuyo Ishida, Takahiro Furukawa, Yoshimichi Miyazaki, Koji Fujita, Ryosuke Miyamoto, Nobuaki Yamamoto, Wataru Sako, Kenta Sato, Kazuya Kondo, Yoshihiko Nishida, Takao Mitsui, Yuishin Izumi, Ryuji Kaji","Waka Sakai, Naoko Matsui, Mitsuyo Ishida, Takahiro Furukawa, Yoshimichi Miyazaki, Koji Fujita, Ryosuke Miyamoto, Nobuaki Yamamoto, Wataru Sako, Kenta Sato, Kazuya Kondo, Yoshihiko Nishida, Takao Mitsui, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2016-02-11","eNeurologicalSci","eNeurologicalSci","Vol.2","null","17","20","eng","true","null","scientific_journal","null","null","10.1016/j.ensci.2016.02.004","2405-6502","null","null","null","null","null" "Fractional anisotropy in the supplementary motor area correlates with disease duration and severity of amyotrophic lateral sclerosis.","Fractional anisotropy in the supplementary motor area correlates with disease duration and severity of amyotrophic lateral sclerosis.","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Amyotrophic lateral sclerosis (ALS) is progressive and fatal neurodegenerative disorder with upper and lower motor neuron signs. There are no biomarkers to track disease progression. To address this issue, we investigated regions in which fractional anisotropy (FA) values derived from diffusion weighted images correlated with both disease severity and duration in ALS patients. Fourteen patients with ALS were enrolled in this study. Voxel-based analysis revealed volume of interests (VOIs) showing significant correlation. Finally, Spearman rank correlation coefficient was assessed between FA value in each VOI and disease severity or duration. In the VOI of left supplementary motor area (SMA), FA value significantly correlated with disease severity and duration both (disease severity, rho = 0.59, p = 0.025; disease duration, rho = -0.69, p = 0.006). The present finding suggested the possibility that the abnormality in motor-related region including SMA could be a candidate for a biomarker to track disease progression.","Amyotrophic lateral sclerosis (ALS) is progressive and fatal neurodegenerative disorder with upper and lower motor neuron signs. There are no biomarkers to track disease progression. To address this issue, we investigated regions in which fractional anisotropy (FA) values derived from diffusion weighted images correlated with both disease severity and duration in ALS patients. Fourteen patients with ALS were enrolled in this study. Voxel-based analysis revealed volume of interests (VOIs) showing significant correlation. Finally, Spearman rank correlation coefficient was assessed between FA value in each VOI and disease severity or duration. In the VOI of left supplementary motor area (SMA), FA value significantly correlated with disease severity and duration both (disease severity, rho = 0.59, p = 0.025; disease duration, rho = -0.69, p = 0.006). The present finding suggested the possibility that the abnormality in motor-related region including SMA could be a candidate for a biomarker to track disease progression.","null","null","2016-01-25","Neurological Sciences","Neurological Sciences","Vol.37","No.4","573","577","eng","true","null","scientific_journal","null","null","10.1007/s10072-016-2487-z","1590-3478","null","null","null","null","null" "Extranodal NK/T-cell lymphoma, nasal type, manifesting as rapidly progressive dementia without any mass or enhancing brain lesion.","Extranodal NK/T-cell lymphoma, nasal type, manifesting as rapidly progressive dementia without any mass or enhancing brain lesion.","Yoshimitsu Shimatani, Yuta Nakano, Naoko Tsuyama, Shigeo Murayama, Ryosuke Oki, Ryosuke Miyamoto, Nagahisa Murakami, Koji Fujita, Syunsuke Watanabe, Hisanori Uehara, Takashi Abe, Hiroyuki Nodera, Toshitaka Kawarai, Yuishin Izumi, Ryuji Kaji","Yoshimitsu Shimatani, Yuta Nakano, Naoko Tsuyama, Shigeo Murayama, Ryosuke Oki, Ryosuke Miyamoto, Nagahisa Murakami, Koji Fujita, Syunsuke Watanabe, Hisanori Uehara, Takashi Abe, Hiroyuki Nodera, Toshitaka Kawarai, Yuishin Izumi, Ryuji Kaji","null","Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools.","Among the many potential etiologies for rapidly progressive dementia (RPD), primary central nervous system extranodal NK/T-cell lymphoma, nasal-type (ENKL) is a rare entity. We present the first reported case of autopsy-proven RPD due to ENKL without any mass or enhancing lesion of the brain. A 54-year-old immunocompetent man presented with RPD, myoclonus and ataxia. The mini-mental state examination (MMSE) score was 22/30. His brain MRI revealed progressive brain atrophy without gadolinium enhancement or mass lesion. Five months after the initial evaluation, cognitive impairment further worsened with an MMSE score of 3/30. At the advanced stage, lumbar MRI showed swollen cauda equina with gadolinium enhancement. The number of Epstein-Barr virus (EBV) DNA in cerebrospinal fluid had gradually increased. Twelve months after onset, the patient died of respiratory failure. Pathological findings revealed that lymphoma cells had diffusely invaded the meninges, parenchyma of the brain, spinal cord and cauda equina. Cells were positive for CD3, CD56 and EBV-encoded small RNAs and negative for CD20. No evidence of malignancy was identified in the visceral organs. This report indicates that ENKL should be recognized as one of the rare causes of RPD. Early testing for EBV-DNA in cerebrospinal fluid and imaging of cauda equina would be useful diagnostic tools.","null","null","2016-01-15","Neuropathology","Neuropathology","Vol.36","No.5","456","463","eng","true","null","scientific_journal","null","null","10.1111/neup.12285","1440-1789","null","null","null","null","null" "The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis","The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","Wataru Sako, Takashi Abe, Yuishin Izumi, Masafumi Harada, Ryuji Kaji","null","Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The ""suspected"" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.","Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The ""suspected"" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.","null","null","2016-01-04","Journal of Clinical Neuroscience","Journal of Clinical Neuroscience","Vol.27","null","110","113","eng","true","null","scientific_journal","null","null","10.1016/j.jocn.2015.08.044","1532-2653","null","null","null","null","null" "Multimodal analysis based on high-field magnetic resonance and motor evoked potentials: A case report of multiple sclerosis","Multimodal analysis based on high-field magnetic resonance and motor evoked potentials: A case report of multiple sclerosis","Shunya Nakane, Kaori Furutani, Masafumi Harada, Ryo Urushihara, Naoko Matsui, Yuishin Izumi, Ryuji Kaji","Shunya Nakane, Kaori Furutani, Masafumi Harada, Ryo Urushihara, Naoko Matsui, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2016-01","Clinical & Experimental Neuroimmunology","Clinical & Experimental Neuroimmunology","Vol.8","No.1","43","46","eng","true","null","scientific_journal","null","null","10.1111/cen3.12352","1759-1961","null","null","null","null","null" "Ocular myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies: Two new cases and a systematic literature review","Ocular myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies: Two new cases and a systematic literature review","Masaki Kamata, Shunya Nakane, Naoko Matsui, Osamu Higuchi, Sakai Waka, Koji Fujita, Yuishin Izumi, Hidenori Matsuo, Ryuji Kaji","Masaki Kamata, Shunya Nakane, Naoko Matsui, Osamu Higuchi, Sakai Waka, Koji Fujita, Yuishin Izumi, Hidenori Matsuo, Ryuji Kaji","null","null","null","null","null","2016-01","Clinical & Experimental Neuroimmunology","Clinical & Experimental Neuroimmunology","Vol.7","No.2","168","173","eng","true","null","scientific_journal","null","null","10.1111/cen3.12296","1759-1961","null","null","null","null","null" "ASL1","ASL1","山本 伸昭, 和泉 唯信, 山本 雄貴, 垂髪 祐樹, 梶 龍兒, 里見 淳一郎, 永廣 信治","Nobuaki Yamamoto, Yuishin Izumi, Y Yamamoto, 垂髪 祐樹, Ryuji Kaji, Junichiro Satomi, Shinji Nagahiro","null","null","null","null","null","2016","臨床神経学","Clinical Neurology","Vol.56","No.3","225","225","jpn","true","null","scientific_journal","null","null","null","0009-918X","null","null","null","null","null" "約14年の経過でポストポリオ症候群が広範に進行した1剖検例","An autopsy case of progressive generalized muscle atrophy over 14 years due to post-polio syndrome","沖 良祐, 内野 彰子, 和泉 唯信, 小川 博久, 村山 繁雄, 梶 龍兒","Ryosuke Oki, Akiko Uchino, Yuishin Izumi, Hirohisa Ogawa, Shigeo Murayama, Ryuji Kaji","null","症例は死亡時74歳の男性である.小児期の急性灰白髄炎罹患後に左下肢麻痺が残存した.60歳頃より四肢筋力低下,72歳頃より呼吸機能障害・嚥下障害が進行し,発症約14年後に死亡した.神経病理学的には脊髄にポリオ後遺症と思われるplaque-like lesionのほか,脊髄全長にわたりグリオーシスを伴う前角細胞脱落を認めたが,Bunina小体やユビキチン・TDP43陽性封入体などamyotrophic lateral sclerosis(ALS)に特徴的とされる構造物は認めなかった.ポストポリオ症候群は稀に呼吸機能障害や嚥下障害が急速に進行して致死的となる場合があり,これらの病理所見はポストポリオ症候群による運動麻痺の進行と関連していると考えられた.","We report the case of a 72-year-old man who had contracted acute paralytic poliomyelitis in his childhood. Thereafter, he had suffered from paresis involving the left lower limb, with no relapse or progression of the disease. He began noticing slowly progressive muscle weakness and atrophy in the upper and lower extremities in his 60s. At the age of 72, muscle weakness developed rapidly, and he demonstrated dyspnea on exertion and dysphagia. He died after about 14 years from the onset of muscle weakness symptoms. Autopsy findings demonstrated motoneuron loss and glial scars not only in the plaque-like lesions in the anterior horns, which were sequelae of old poliomyelitis, but also throughout the spine. No Bunina bodies, TDP-43, and ubiquitin inclusions were found. Post-polio syndrome is rarely fatal due to rapid progressive dyspnea and dysphagia. Thus, the pathological findings in the patient are considered to be related to the development of muscle weakness.","null","null","2016","臨床神経学","Clinical Neurology","Vol.56","No.1","12","16","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.cn-000761","0009-918X","null","null","null","null","null" "Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis","Intramuscular dissociation of echogenicity in the triceps surae characterizes sporadic inclusion body myositis","Hiroyuki Nodera, Naoko Takamatsu, Naoko Matsui, Atsuko Mori, Yuka Terasawa, Yoshimitsu Shimatani, Yusuke Osaki, Keiko Maruyama, Yuishin Izumi, Ryuji Kaji","Hiroyuki Nodera, Naoko Takamatsu, Naoko Matsui, Atsuko Mori, Yuka Terasawa, Yoshimitsu Shimatani, Yusuke Osaki, Keiko Maruyama, Yuishin Izumi, Ryuji Kaji","null","Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.","Differential diagnosis of sporadic inclusion body myositis (s-IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s-IBM by muscle sonography could be a unique diagnostic feature. Sonography of the lower leg and forearm was performed in patients with s-IBM, PM/DM and control subjects (n = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer-assisted histogram analysis. Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s-IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s-IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s-IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s-IBM and DM/PM was greatest between the gastrocnemius-soleus EIs (0.843; P = 0.006). High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s-IBM over PM/DM.","null","null","2016","European Journal of Neurology","European Journal of Neurology","Vol.23","No.3","588","596","eng","true","null","scientific_journal","null","null","10.1111/ene.12899","1468-1331","null","null","null","null","null" "Predictors of a favorable outcome after recanalization in patients with cerebral major vessel occlusion","Predictors of a favorable outcome after recanalization in patients with cerebral major vessel occlusion","Nobuaki Yamamoto, Junichiro Satomi, Yuishin Izumi, Yamamoto Yuki, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Junichiro Satomi, Yuishin Izumi, Yamamoto Yuki, Shinji Nagahiro, Ryuji Kaji","null","Although tissue plasminogen activator and endovascular treatment were reported to be useful for recanalization in patients with major vessel occlusion (MVO), the outcome in some patients with recanalization was unfavorable. We could detect prolongation of the ipsilateral posterior cerebral artery (PCA) to the ischemic side on magnetic resonance angiography in some patients (ipsilateral-PCA sign). We investigated the predictors including radiological findings for a favorable outcome after successful recanalization. We included 76 patients with MVO of the anterior circulation and documented recanalization by treatment. We divided our patients into 2 groups: group F (modified Rankin scale [mRS] score = 0-2) and group UF (mRS score = 3-6). We compared biomarkers between the groups. National Institutes of Health Stroke Scale (NIHSS) score before treatment in group F (8.5) was lower than that in group UF (16.0; P <.001). Sensitivity of the ipsilateral-PCA sign was commonly associated with group F (67.5% versus 19.4%, P <.001), and specificity of the sign was 80.6%. Absence of infarcts in the anterior cerebral artery (ACA) territory and ACA occlusion were also associated with a favorable outcome. In multivariate analysis, the ipsilateral-PCA sign and NIHSS score (≤ 10) were independent predictors of favorable outcome (odds ratio = 9.92, 95% confidence interval [CI] 2.71-36.23, P = .001; and odds ratio = 9.15, 95% CI 2.44-34.36, P = .001, respectively) The ipsilateral-PCA sign and low NIHSS score (≤ 10) were predictors of a favorable outcome in patients with MVO and documented recanalization by treatments.","Although tissue plasminogen activator and endovascular treatment were reported to be useful for recanalization in patients with major vessel occlusion (MVO), the outcome in some patients with recanalization was unfavorable. We could detect prolongation of the ipsilateral posterior cerebral artery (PCA) to the ischemic side on magnetic resonance angiography in some patients (ipsilateral-PCA sign). We investigated the predictors including radiological findings for a favorable outcome after successful recanalization. We included 76 patients with MVO of the anterior circulation and documented recanalization by treatment. We divided our patients into 2 groups: group F (modified Rankin scale [mRS] score = 0-2) and group UF (mRS score = 3-6). We compared biomarkers between the groups. National Institutes of Health Stroke Scale (NIHSS) score before treatment in group F (8.5) was lower than that in group UF (16.0; P <.001). Sensitivity of the ipsilateral-PCA sign was commonly associated with group F (67.5% versus 19.4%, P <.001), and specificity of the sign was 80.6%. Absence of infarcts in the anterior cerebral artery (ACA) territory and ACA occlusion were also associated with a favorable outcome. In multivariate analysis, the ipsilateral-PCA sign and NIHSS score (≤ 10) were independent predictors of favorable outcome (odds ratio = 9.92, 95% confidence interval [CI] 2.71-36.23, P = .001; and odds ratio = 9.15, 95% CI 2.44-34.36, P = .001, respectively) The ipsilateral-PCA sign and low NIHSS score (≤ 10) were predictors of a favorable outcome in patients with MVO and documented recanalization by treatments.","null","null","2015-12","Journal of Stroke & Cerebrovascular Diseases","Journal of Stroke & Cerebrovascular Diseases","Vol.24","No.12","2793","2799","eng","true","null","scientific_journal","null","null","10.1016/j.jstrokecerebrovasdis.2015.08.012","1532-8511","null","null","null","null","null" "Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation.","Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation.","Toshitaka Kawarai, Ryosuke Miyamoto, Atsuko Mori, Ryosuke Oki, Ai Tsukamoto-Miyashiro, Naoko Matsui, Yoshimichi Miyazaki, Antonio Orlacchio, Yuishin Izumi, Yoshihiko Nishida, Ryuji Kaji","Toshitaka Kawarai, Ryosuke Miyamoto, Atsuko Mori, Ryosuke Oki, Ai Tsukamoto-Miyashiro, Naoko Matsui, Yoshimichi Miyazaki, Antonio Orlacchio, Yuishin Izumi, Yoshihiko Nishida, Ryuji Kaji","null","We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis.","We identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866+1G>A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis.","null","null","2015-10-30","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.359","No.1-2","250","255","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2015.10.045","1878-5883","null","null","null","null","null" "The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments.","The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments.","Tomokazu Nishikawa, Tetsuya Takahashi, Masahiro Nakamori, Naohisa Hosomi, Hirofumi Maruyama, Yoshimichi Miyazaki, Yuishin Izumi, Masayasu Matsumoto","Tomokazu Nishikawa, Tetsuya Takahashi, Masahiro Nakamori, Naohisa Hosomi, Hirofumi Maruyama, Yoshimichi Miyazaki, Yuishin Izumi, Masayasu Matsumoto","null","These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation. This article is protected by copyright. All rights reserved.","These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation. This article is protected by copyright. All rights reserved.","null","null","2015-10-26","Neuropathology and Applied Neurobiology","Neuropathology and Applied Neurobiology","Vol.42","No.7","639","653","eng","true","null","scientific_journal","null","null","10.1111/nan.12288","1365-2990","null","null","null","null","null" "Autopsy case of severe generalized dystonia and static ataxia with marked cerebellar atrophy.","Autopsy case of severe generalized dystonia and static ataxia with marked cerebellar atrophy.","Ryosuke Miyamoto, Hiroyuki Sumikura, Toshiaki Takeuchi, Mitsuru Sanada, Koji Fujita, Toshitaka Kawarai, Hideo Mure, Ryoma Morigaki, Satoshi Goto, Shigeo Murayama, Yuishin Izumi, Ryuji Kaji","Ryosuke Miyamoto, Hiroyuki Sumikura, Toshiaki Takeuchi, Mitsuru Sanada, Koji Fujita, Toshitaka Kawarai, Hideo Mure, Ryoma Morigaki, Satoshi Goto, Shigeo Murayama, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2015-09-25","Neurology","Neurology","Vol.85","No.17","1522","1524","eng","true","null","scientific_journal","null","null","10.1212/WNL.0000000000002061","1526-632X","null","null","null","null","null" "The effect of tremor onset on middle cerebellar peduncle of Parkinson's disease.","The effect of tremor onset on middle cerebellar peduncle of Parkinson's disease.","Wataru Sako, Nagahisa Murakami, Yoshimichi Miyazaki, Takashi Abe, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yoshimichi Miyazaki, Takashi Abe, Masafumi Harada, Yuishin Izumi, Ryuji Kaji","null","The majority of studies of Parkinson's disease (PD) focused on basal ganglia initially; however, accumulating evidence suggests cerebellar involvement in pathophysiology. We aimed to investigate the effects of tremor onset on middle cerebellar peduncle (MCP) width of PD patients and of disease duration on differential diagnosis. We measured MCP width of 81 PD, 34 multiple system atrophy (MSA) and 16 normal controls, using MRI. A meta-analysis was performed including two previous and the present studies. We carried out correlation analysis between disease duration and MCP width separately in subgroup of PD with or without tremor onset. Receiver operating characteristic curves were analyzed. Our meta-analysis indicated that MCP width was significantly smaller in MSA relative to PD with homogeneous studies. There was significant correlation between disease duration and MCP width in PD without tremor onset. In contrast, there was no correlation observed in PD with tremor onset. Subclassification according to disease duration showed improved area under curve of PD vs. MSA with predominant parkinsonian features. MCP width could be a valuable tool for differential diagnosis. Our finding suggested that MCP was impaired in advanced stage of PD without tremor onset as part of the abnormality of the cerebellar system.","The majority of studies of Parkinson's disease (PD) focused on basal ganglia initially; however, accumulating evidence suggests cerebellar involvement in pathophysiology. We aimed to investigate the effects of tremor onset on middle cerebellar peduncle (MCP) width of PD patients and of disease duration on differential diagnosis. We measured MCP width of 81 PD, 34 multiple system atrophy (MSA) and 16 normal controls, using MRI. A meta-analysis was performed including two previous and the present studies. We carried out correlation analysis between disease duration and MCP width separately in subgroup of PD with or without tremor onset. Receiver operating characteristic curves were analyzed. Our meta-analysis indicated that MCP width was significantly smaller in MSA relative to PD with homogeneous studies. There was significant correlation between disease duration and MCP width in PD without tremor onset. In contrast, there was no correlation observed in PD with tremor onset. Subclassification according to disease duration showed improved area under curve of PD vs. MSA with predominant parkinsonian features. MCP width could be a valuable tool for differential diagnosis. Our finding suggested that MCP was impaired in advanced stage of PD without tremor onset as part of the abnormality of the cerebellar system.","null","null","2015-08-28","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.358","No.1-2","172","177","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2015.08.1531","1878-5883","null","null","null","null","null" "CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy.","CSF cytokine profile distinguishes multifocal motor neuropathy from progressive muscular atrophy.","Takahiro Furukawa, Naoko Matsui, Koji Fujita, Hiroyuki Nodera, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Yuishin Izumi, Ryuji Kaji","Takahiro Furukawa, Naoko Matsui, Koji Fujita, Hiroyuki Nodera, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Yuishin Izumi, Ryuji Kaji","null","The CSF cytokine profile of patients with MMN is distinct from that of patients with PMA and ALS. The similarity of the cytokine profiles between patients with PMA and ALS suggests that PMA shares common immunologic features with ALS in the CNS, even without clinical evidence of upper motor neuron involvement.","The CSF cytokine profile of patients with MMN is distinct from that of patients with PMA and ALS. The similarity of the cytokine profiles between patients with PMA and ALS suggests that PMA shares common immunologic features with ALS in the CNS, even without clinical evidence of upper motor neuron involvement.","null","null","2015-08-06","Neurology® Neuroimmunology & Neuroinflammation","Neurology® Neuroimmunology & Neuroinflammation","Vol.2","No.5","e138","e138","eng","true","null","scientific_journal","null","null","10.1212/NXI.0000000000000138","2332-7812","null","null","null","null","null" "A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability.","A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability.","Toshitaka Kawarai, Atsushi Tajima, Yukiko Kuroda, Naoki Saji, Antonio Orlacchio, Hideo Terasawa, Hirotaka Shimizu, Yasushi Kita, Yuishin Izumi, Takao Mitsui, Issei Imoto, Ryuji Kaji","Toshitaka Kawarai, Atsushi Tajima, Yukiko Kuroda, Naoki Saji, Antonio Orlacchio, Hideo Terasawa, Hirotaka Shimizu, Yasushi Kita, Yuishin Izumi, Takao Mitsui, Issei Imoto, Ryuji Kaji","null","Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues.","Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues.","null","null","2015-07-08","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","Vol.87","No.6","656","662","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2014-309828","1468-330X","null","null","null","null","null" "Neurofilament light chain level in cerebrospinal fluid can differentiate Parkinson's disease from atypical parkinsonism: Evidence from a meta-analysis.","Neurofilament light chain level in cerebrospinal fluid can differentiate Parkinson's disease from atypical parkinsonism: Evidence from a meta-analysis.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","A reliable test that facilitates the accurate diagnosis of Parkinson's and disorders will help with both, clinical management and therapeutic research. In this context, neurofilament light chain (NFL) is candidate for a biomarker in cerebrospinal fluid (CSF). A comprehensive literature search yielded 4 eligible studies. We expressed between-group difference of NFL concentration in CSF as the standardized mean difference. Four studies involved 166 Parkinson's disease (PD), 116 multiple system atrophy (MSA) and 73 progressive supranuclear palsy (PSP) patients. Patients with MSA showed higher concentration of NFL concentration in CSF than those with PD (standardized mean difference=1.60, P<0.0001). These studies were homogeneous (P=0.17). NFL in CSF in PSP was significantly elevated relative to PD with homogeneous studies (standardized mean difference=2.04, P<0.0001; P=0.99). The present meta-analysis suggested that NFL concentration in CSF in MSA and PSP was significantly increased relative to PD, and that this could help us to separate PD from atypical parkinsonian syndromes.","A reliable test that facilitates the accurate diagnosis of Parkinson's and disorders will help with both, clinical management and therapeutic research. In this context, neurofilament light chain (NFL) is candidate for a biomarker in cerebrospinal fluid (CSF). A comprehensive literature search yielded 4 eligible studies. We expressed between-group difference of NFL concentration in CSF as the standardized mean difference. Four studies involved 166 Parkinson's disease (PD), 116 multiple system atrophy (MSA) and 73 progressive supranuclear palsy (PSP) patients. Patients with MSA showed higher concentration of NFL concentration in CSF than those with PD (standardized mean difference=1.60, P<0.0001). These studies were homogeneous (P=0.17). NFL in CSF in PSP was significantly elevated relative to PD with homogeneous studies (standardized mean difference=2.04, P<0.0001; P=0.99). The present meta-analysis suggested that NFL concentration in CSF in MSA and PSP was significantly increased relative to PD, and that this could help us to separate PD from atypical parkinsonian syndromes.","null","null","2015-04-07","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.352","No.1-2","84","87","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2015.03.041","1878-5883","null","null","null","null","null" "Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?","Is the Susceptibility Vessel Sign on 3-Tesla Magnetic Resonance T2*-Weighted Imaging a Useful Tool to Predict Recanalization in Intravenous Tissue Plasminogen Activator?","Nobuaki Yamamoto, Junichiro Satomi, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Junichiro Satomi, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","null","The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.","The aim of this study was to investigate the independent factors associated with the absence of recanalization approximately 24 h after intravenous administration of tissue-type plasminogen activator (IV TPA). The previous studies have been conducted using 1.5-Tesla (T) magnetic resonance imaging (MRI). We studied whether the characteristics of 3-T MRI findings were useful to predict outcome and recanalization after IV tPA. Patients with internal carotid artery (ICA) or middle cerebral artery (MCA) (horizontal portion, M1; Sylvian portion, M2) occlusion and treated by IV tPA were enrolled. We studied whether the presence of susceptibility vessel sign (SVS) at M1 and low clot burden score on T2*-weighted imaging (T2*-CBS) on 3-T MRI were associated with the absence of recanalization. A total of 49 patients were enrolled (27 men; mean age, 73.9 years). MR angiography obtained approximately 24 h after IV tPA revealed recanalization in 21 (42.9 %) patients. Independent factors associated with the absence of recanalization included ICA or proximal M1 occlusion (odds ratio, 69.6; 95 % confidence interval, 5.05-958.8, p = 0.002). In this study, an independent factor associated with the absence of recanalization may be proximal occlusion of the cerebral arteries rather than SVS in the MCA or low T2*-CBS on 3-T MRI.","null","null","2014-12-18","Clinical Neuroradiology","Clinical Neuroradiology","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1007/s00062-014-0363-x","1869-1447","null","null","null","null","null" "Val66Met polymorphism of brain-derived neurotrophic factor is associated with idiopathic dystonia.","Val66Met polymorphism of brain-derived neurotrophic factor is associated with idiopathic dystonia.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","The Val66Met (G196A; rs6265) single nucleotide polymorphism of brain-derived neurotrophic factor (BDNF) affects morphology and neuronal activity, and is expected to be associated with central nervous system disorders. However, it remains controversial whether Val66Met polymorphism is a risk factor for idiopathic dystonia. We aimed to clarify the impact of BDNF polymorphism on idiopathic dystonia. A literature search of PubMed was carried out. A random-effects model was employed for the meta-analysis. A pooled odds ratio (OR) was calculated along with 95% confidence intervals (CI) to reflect the risk of idiopathic dystonia in each genotype (GG, AG, AA) or minor allele. The proportion of variation due to heterogeneity was computed and expressed as I(2). Five case-control studies, comprising a total sample size of 1804 subjects (784 idiopathic dystonia patients, 1020 normal controls), were included in this meta-analysis. AA genotype was significantly more frequent in patients with idiopathic dystonia (OR=1.47, 95% CI 1.09-1.99, p=0.01, four studies, n=1716). This finding was derived from homogeneous studies (p=0.97, I(2)=0%). Our meta-analysis has revealed a significant overall effect of the AA genotype on the development of idiopathic dystonia.","The Val66Met (G196A; rs6265) single nucleotide polymorphism of brain-derived neurotrophic factor (BDNF) affects morphology and neuronal activity, and is expected to be associated with central nervous system disorders. However, it remains controversial whether Val66Met polymorphism is a risk factor for idiopathic dystonia. We aimed to clarify the impact of BDNF polymorphism on idiopathic dystonia. A literature search of PubMed was carried out. A random-effects model was employed for the meta-analysis. A pooled odds ratio (OR) was calculated along with 95% confidence intervals (CI) to reflect the risk of idiopathic dystonia in each genotype (GG, AG, AA) or minor allele. The proportion of variation due to heterogeneity was computed and expressed as I(2). Five case-control studies, comprising a total sample size of 1804 subjects (784 idiopathic dystonia patients, 1020 normal controls), were included in this meta-analysis. AA genotype was significantly more frequent in patients with idiopathic dystonia (OR=1.47, 95% CI 1.09-1.99, p=0.01, four studies, n=1716). This finding was derived from homogeneous studies (p=0.97, I(2)=0%). Our meta-analysis has revealed a significant overall effect of the AA genotype on the development of idiopathic dystonia.","null","null","2014-12-15","Journal of Clinical Neuroscience","Journal of Clinical Neuroscience","Vol.22","No.3","575","577","eng","true","null","scientific_journal","null","null","10.1016/j.jocn.2014.08.014","1532-2653","null","null","null","null","null" "The two-1 layered susceptibility vessel sign on 3-tesla T2*-weighted imaging is a predictive biomarker of stroke subtype","The two-1 layered susceptibility vessel sign on 3-tesla T2*-weighted imaging is a predictive biomarker of stroke subtype","Nobuaki Yamamoto, Junichiro Satomi, Yoshiteru Tada, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Junichiro Satomi, Yoshiteru Tada, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","null","A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism. Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism. We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%; P<0.001). The specificity and diagnostic odds ratio for 2-layered SVS for cardioembolism were 97.1% and 25.1; for SVS they were 42.0% and 2.1, respectively. The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.","A susceptibility vessel sign (SVS) on 1.5-tesla (T)-T2*-weighted images may predict cardioembolism. It has also been detected in patients with large artery atherosclerosis. In patients with major vessel occlusion, the SVS was comprised 2 layers on 3T-T2*-weighted images. We assessed the efficacy of 2-layered SVS on 3T-T2*-weighted imaging scans for predicting cardioembolism. Our study included 132 patients who had ischemic stroke within the preceding 24 hours and presented with internal carotid artery or middle cerebral artery occlusion because of cardioembolism or large artery atherosclerosis. We compared 2-layered SVS and SVS on 3T-T2*-weighted imaging scans for their sensitivity, specificity, and diagnostic odds ratio for predicting cardioembolism. We enrolled 132 patients (72 men; mean age, 74.5 years); of these, 63 (47.7%) were presented with cardioembolism. Although the sensitivity of SVS and 2-layered SVS for cardioembolism and large artery atherosclerosis was not statistically different (74.6% and 58.0%, respectively), the sensitivity of 2-layered SVS was significantly higher in patients with cardioembolism (42.9%) than those with large artery atherosclerosis (2.9%; P<0.001). The specificity and diagnostic odds ratio for 2-layered SVS for cardioembolism were 97.1% and 25.1; for SVS they were 42.0% and 2.1, respectively. The specificity of 2-layered SVS for cardioembolism was high. It may be useful for predicting cardioembolism and for the management of patients with acute ischemic stroke.","null","null","2014-12-04","Stroke","Stroke","Vol.46","No.1","269","271","eng","true","null","scientific_journal","null","null","10.1161/STROKEAHA.114.007227","1524-4628","null","null","null","null","null" "脳梗塞発症後早期からの抗血小板薬使用が予後に及ぼす影響の検討","脳梗塞発症後早期からの抗血小板薬使用が予後に及ぼす影響の検討","山本 伸昭, 里見 淳一郎, 寺澤 由佳, 曽我部 周, 中島 公平, 佐藤 泰仁, 板東 一彦, 阿川 昌仁, 浅野 登, 本藤 秀樹, 和泉 唯信, 梶 龍兒, 永廣 信治","Nobuaki Yamamoto, Junichiro Satomi, Yuka Terasawa, Sogabe Syu, Kohhei Nakajima, Yasuhito Sato, Bando Kazuhiko, Agawa Masahito, Asano Noboru, Hondo Hideki, Yuishin Izumi, Ryuji Kaji, Shinji Nagahiro","null","null","null","null","null","2014-11-25","脳卒中","Japanese Journal of Stroke","Vol.36","No.6","419","424","jpn","true","null","scientific_journal","null","null","10.3995/jstroke.36.419","1883-1923","null","null","null","null","null" "Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries","Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries","Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Sakai Waka, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Sakai Waka, Masafumi Harada, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","null","It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries. We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI). Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade ≥ 2 versus PVH grade ≤ 1, odds ratio 6.72, P = .006; with stroke versus without stroke, odds ratio .21, P = .049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge. PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.","It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries. We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI). Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade ≥ 2 versus PVH grade ≤ 1, odds ratio 6.72, P = .006; with stroke versus without stroke, odds ratio .21, P = .049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge. PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.","null","null","2014-09","Journal of Stroke & Cerebrovascular Diseases","Journal of Stroke & Cerebrovascular Diseases","Vol.23","No.8","2151","2155","eng","true","null","scientific_journal","null","null","10.1016/j.jstrokecerebrovasdis.2014.04.011","1532-8511","null","null","null","null","null" "Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy.","Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy.","Takahiro Furukawa, Naoko Matsui, Koji Fujita, Ai Miyashiro, Hiroyuki Nodera, Yuishin Izumi, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Ryuji Kaji","Takahiro Furukawa, Naoko Matsui, Koji Fujita, Ai Miyashiro, Hiroyuki Nodera, Yuishin Izumi, Fumitaka Shimizu, Katsuichi Miyamoto, Yukitoshi Takahashi, Takashi Kanda, Susumu Kusunoki, Ryuji Kaji","null","Proinflammatory cytokines may contribute to peripheral nerve demyelination in MMN.","Proinflammatory cytokines may contribute to peripheral nerve demyelination in MMN.","null","null","2014-08-04","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.346","No.1-2","75","79","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2014.07.059","1878-5883","null","null","null","null","null" "抗利尿ホルモン分泌異常症候群で発症し,橋中心・橋外髄鞘崩壊症を合併した視神経脊髄炎関連疾患の1例","Case of neuromyelitis optica spectrum disorder associated with central pontine and extrapontine myelinolysis preceded by syndrome of inappropriate antidiuretic hormone secretion","酒井 和香, 松井 尚子, 藤田 浩司, 和泉 唯信, 西田 喜彦, 高橋 利幸, 神林 崇, 梶 龍兒","酒井 和香, Naoko Matsui, Koji Fujita, Yuishin Izumi, 西田 喜彦, 高橋 利幸, 神林 崇, Ryuji Kaji","null","A 36-year-old woman complained of general malaise. She presented with hyponatremia and plasma osmotic pressure was lower than urinary osmotic pressure. In addition, serum antidiuretic hormone level was higher than the measurement sensitivity. She was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). She fell into a coma despite correction of serum sodium level. Brain magnetic resonance imaging (MRI) revealed high signal intensities in the cerebral cortex, striatum, thalamus, hypothalamus, midbrain, and pons in fluid-attenuated inversion recovery images. Spinal MRI revealed a longitudinally extending lesion in the cervical cord. Serum sample was positive for anti-aquaporin-4 antibody, supporting the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) combined with central pontine and extrapontine myelinolysis. In patients with NMOSD, the immune reaction can gradually cause destructive changes of the hypothalamus and lead to unstable ADH secretion in the absence of immunomodulatory treatment.","A 36-year-old woman complained of general malaise. She presented with hyponatremia and plasma osmotic pressure was lower than urinary osmotic pressure. In addition, serum antidiuretic hormone level was higher than the measurement sensitivity. She was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). She fell into a coma despite correction of serum sodium level. Brain magnetic resonance imaging (MRI) revealed high signal intensities in the cerebral cortex, striatum, thalamus, hypothalamus, midbrain, and pons in fluid-attenuated inversion recovery images. Spinal MRI revealed a longitudinally extending lesion in the cervical cord. Serum sample was positive for anti-aquaporin-4 antibody, supporting the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) combined with central pontine and extrapontine myelinolysis. In patients with NMOSD, the immune reaction can gradually cause destructive changes of the hypothalamus and lead to unstable ADH secretion in the absence of immunomodulatory treatment.","null","null","2014-08-02","臨床神経学","Clinical Neurology","Vol.54","No.7","556","560","jpn","true","null","scientific_journal","null","null","10.5692/clinicalneurol.54.556","1882-0654","null","null","null","null","null" "The difference in putamen volume between MSA and PD: Evidence from a meta-analysis.","The difference in putamen volume between MSA and PD: Evidence from a meta-analysis.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","Six studies, comprising a sample size of 84 MSA and 180 PD, were included in this meta-analysis. The overall effect indicated that putamen volume in MSA was significantly more reduced than that in PD with heterogeneous studies (P = 0.0004, 6 studies, n = 264, I(2) = 87%). A subgroup analysis revealed that the category of ""Hoehn-Yahr stage of PD"" showed a significant subgroup difference with a significant subgroup summary effect (subgroup difference: P = 0.003).","Our findings based on group-level analysis suggested that volumetry of the putamen could be useful for differential diagnosis between MSA and PD at the early stage of disease, and also help to enroll more accurate disease group for disease modifying study in future.","null","null","2014-05-09","Parkinsonism & Related Disorders","Parkinsonism & Related Disorders","Vol.20","No.8","873","877","eng","true","null","scientific_journal","null","null","10.1016/j.parkreldis.2014.04.028","1873-5126","null","null","null","null","null" "MIBG Myocardial Scintigraphy can Predict the Occurrence of Wearing-off Phenomenon in Early-stage Parkinsons Disease","MIBG Myocardial Scintigraphy can Predict the Occurrence of Wearing-off Phenomenon in Early-stage Parkinsons Disease","Yoshimichi Miyazaki, Wataru Sako, Kenta Sato, Yuishin Izumi, Ryuji Kaji","Yoshimichi Miyazaki, Wataru Sako, Kenta Sato, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2014-04-18","Journal of Neurological Disorders","Journal of Neurological Disorders","Vol.2","null","154","154","eng","true","null","scientific_journal","null","null","10.4172/2329-6895.1000154","2329-6895","null","null","null","null","null" "Are multifocal motor neuropathy patients underdiagnosed? An epidemiological survey in Japan","Are multifocal motor neuropathy patients underdiagnosed? An epidemiological survey in Japan","Ai Miyashiro, Naoko Matsui, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kawabata, Tomihiro Imai, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Maezaki, Jun Kawamata, Takefumi Hitomi, Nobuo Kohara, Kimiyoshi Arimura, Shuji Hashimoto, Kokichi Arisawa, Susumu Kusunoki, Ryuji Kaji","Ai Miyashiro, Naoko Matsui, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kawabata, Tomihiro Imai, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Maezaki, Jun Kawamata, Takefumi Hitomi, Nobuo Kohara, Kimiyoshi Arimura, Shuji Hashimoto, Kokichi Arisawa, Susumu Kusunoki, Ryuji Kaji","null","Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin (IVIg) was also taken into consideration in the diagnosis of MMN. The ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63 ALS patients per 100,000 population. The frequency of MMN patients was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some centers.","Our objective was to do an epidemiologic survey of patients with multifocal motor neuropathy (MMN) in comparison with those with amyotrophic lateral sclerosis (ALS) in Japan. In this retrospective study, we examined 46 patients with MMN and 1,051 patients with ALS from major neuromuscular centers in Japan from 2005 to 2009. Diagnosis was based on the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) and the revised El Escorial criteria. The efficacy of intravenous immunoglobulin (IVIg) was also taken into consideration in the diagnosis of MMN. The ratio of MMN to ALS patients (0-0.10) varied among the centers, but mostly converged to 0.05. The prevalence was estimated to be 0.29 MMN patients and 6.63 ALS patients per 100,000 population. The frequency of MMN patients was around 1 out of 20 ALS patients, and MMN was possibly underdiagnosed in some centers.","null","null","2014-03","Muscle & Nerve","Muscle & Nerve","Vol.49","No.3","357","361","eng","true","null","scientific_journal","null","null","10.1002/mus.23930","0148-639X","null","null","null","null","null" "MRI Can Detect Nigral Volume Loss in Patients with Parkinson's Disease: Evidence from a Meta-Analysis.","MRI Can Detect Nigral Volume Loss in Patients with Parkinson's Disease: Evidence from a Meta-Analysis.","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Nagahisa Murakami, Yuishin Izumi, Ryuji Kaji","null","Background: Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in substantia nigra compacta. However, it is still a contentious issue whether magnetic resonance imaging (MRI) can detect the nigral volume loss in PD patients. Objective: We synthesized the results of published research on SN volumetry using a meta-analysis method in order to clarify this issue. Methods: A comprehensive literature search yielded 8 eligible studies. Nigral size was expressed as the standardized mean difference (SMD) between normal controls and PD patients. In addition, subgroup analysis was performed in order to identify the best condition for nigral volumetry. The proportion of variation due to heterogeneity was computed and expressed as I2. Results: Eight studies involved 172 normal control and 193 PD patients. The overall effect indicated that nigral volume in PD was significantly smaller than normal controls with homogeneous studies (SMD = -0.65, P < 0.0001; I2 = 47%). Maximum of subgroup effect was observed in 'volumetry' among three approaches ('thickness': SMD = -0.35, P = 0.18, I2 = not available; 'area': SMD = -0.39, P = 0.14, I2 = 0%; 'volumetry': SMD = -0.82, P = 0.0006, I2 = 56%). The approach including T1-weighted images (T1WI) showed larger effect ('with T1WI': SMD = -1.11, P < 0.00001, I2 = 36%; 'without T1WI': SMD = -0.32, P = 0.04, I2 = 0%). Conclusions: These findings suggest that volumetry based on T1WI could be the most sensitive option to identify nigral volume loss in PD patients.","Background: Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in substantia nigra compacta. However, it is still a contentious issue whether magnetic resonance imaging (MRI) can detect the nigral volume loss in PD patients. Objective: We synthesized the results of published research on SN volumetry using a meta-analysis method in order to clarify this issue. Methods: A comprehensive literature search yielded 8 eligible studies. Nigral size was expressed as the standardized mean difference (SMD) between normal controls and PD patients. In addition, subgroup analysis was performed in order to identify the best condition for nigral volumetry. The proportion of variation due to heterogeneity was computed and expressed as I2. Results: Eight studies involved 172 normal control and 193 PD patients. The overall effect indicated that nigral volume in PD was significantly smaller than normal controls with homogeneous studies (SMD = -0.65, P < 0.0001; I2 = 47%). Maximum of subgroup effect was observed in 'volumetry' among three approaches ('thickness': SMD = -0.35, P = 0.18, I2 = not available; 'area': SMD = -0.39, P = 0.14, I2 = 0%; 'volumetry': SMD = -0.82, P = 0.0006, I2 = 56%). The approach including T1-weighted images (T1WI) showed larger effect ('with T1WI': SMD = -1.11, P < 0.00001, I2 = 36%; 'without T1WI': SMD = -0.32, P = 0.04, I2 = 0%). Conclusions: These findings suggest that volumetry based on T1WI could be the most sensitive option to identify nigral volume loss in PD patients.","null","null","2014-02-27","Journal of Parkinson's Disease","Journal of Parkinson's Disease","null","null","null","null","eng","true","null","scientific_journal","null","null","10.3233/JPD-130332","1877-718X","null","null","null","null","null" "Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography.","Thinning of cervical nerve roots and peripheral nerves in ALS as measured by sonography.","Hiroyuki Nodera, Naoko Takamatsu, Yoshimitsu Shimatani, Atsuko Mori, Kenta Sato, Masaya Oda, Yuka Terasawa, Yuishin Izumi, Ryuji Kaji","Hiroyuki Nodera, Naoko Takamatsu, Yoshimitsu Shimatani, Atsuko Mori, Kenta Sato, Masaya Oda, Yuka Terasawa, Yuishin Izumi, Ryuji Kaji","null","Sonographic evaluation of nerve roots and peripheral nerves may be a useful disease marker in ALS to confirm the diagnosis and to potentially monitor the disease progression.","Sonographic evaluation of nerve roots and peripheral nerves may be a useful disease marker in ALS to confirm the diagnosis and to potentially monitor the disease progression.","null","null","2014-02-24","Clinical Neurophysiology","Clinical Neurophysiology","Vol.125","No.9","1906","1911","eng","true","null","scientific_journal","null","null","10.1016/j.clinph.2014.01.033","1872-8952","null","null","null","null","null" "Comparison between botulinum neurotoxin type A2 and type A1 by electrophysiological study in healthy individuals.","Comparison between botulinum neurotoxin type A2 and type A1 by electrophysiological study in healthy individuals.","Yohei Mukai, Yoshimitsu Shimatani, Wataru Sako, Kotaro Asanuma, Hiroyuki Nodera, Takashi Sakamoto, Yuishin Izumi, Tomoko Kohda, Shunji Kozaki, Ryuji Kaji","Yohei Mukai, Yoshimitsu Shimatani, Wataru Sako, Kotaro Asanuma, Hiroyuki Nodera, Takashi Sakamoto, Yuishin Izumi, Tomoko Kohda, Shunji Kozaki, Ryuji Kaji","null","Botulinum neurotoxin type A1 (BoNTs/A1) and type B (BoNT/B) have been used for treating hyperactive muscle contractions. In the present study, we compared the effect of botulinum neurotoxin subtype A2 (6.5 mouse LD50 units A2 neurotoxin, A2NTX) and onabotulinumtoxinA (10 mouse LD50 units BoNT/A1 product) by measuring the compound muscle action potentials (CMAPs) before and after administration. In total, 8 healthy subjects were examined in the present study. A2NTX was injected into the extensor digitorum brevis (EDB) muscle, followed by onabotulinumtoxinA injection into the contralateral EDB muscle after 16 weeks. The CMAP amplitudes from the EDB, abductor hallucis (AH), and abductor digiti minimi pedis (ADM) muscles were measured after each BoNT injection on days 1, 3, 7, 14, 28, 56, 84, and 112 to assess the effect of the toxin. On day 14, both A2NTX and onabotulinumtoxinA produced an approximately 70% decline in EDB CMAP amplitude compared to the baseline values; significant reduction of the CMAP continued through day 112. The CMAP amplitudes from neighboring muscles (AH and ADM) remained intact throughout the study period, except for a slight but significant drop at day 28 after onabotulinumtoxinA injection compared to A2NTX. The current findings indicate that small doses (6.5 units and 10 units) of A2NTX and onabotulinumtoxinA have at least comparable onset and duration of action, although similar clinical effects were obtained with lower dose using A2NTX.","Botulinum neurotoxin type A1 (BoNTs/A1) and type B (BoNT/B) have been used for treating hyperactive muscle contractions. In the present study, we compared the effect of botulinum neurotoxin subtype A2 (6.5 mouse LD50 units A2 neurotoxin, A2NTX) and onabotulinumtoxinA (10 mouse LD50 units BoNT/A1 product) by measuring the compound muscle action potentials (CMAPs) before and after administration. In total, 8 healthy subjects were examined in the present study. A2NTX was injected into the extensor digitorum brevis (EDB) muscle, followed by onabotulinumtoxinA injection into the contralateral EDB muscle after 16 weeks. The CMAP amplitudes from the EDB, abductor hallucis (AH), and abductor digiti minimi pedis (ADM) muscles were measured after each BoNT injection on days 1, 3, 7, 14, 28, 56, 84, and 112 to assess the effect of the toxin. On day 14, both A2NTX and onabotulinumtoxinA produced an approximately 70% decline in EDB CMAP amplitude compared to the baseline values; significant reduction of the CMAP continued through day 112. The CMAP amplitudes from neighboring muscles (AH and ADM) remained intact throughout the study period, except for a slight but significant drop at day 28 after onabotulinumtoxinA injection compared to A2NTX. The current findings indicate that small doses (6.5 units and 10 units) of A2NTX and onabotulinumtoxinA have at least comparable onset and duration of action, although similar clinical effects were obtained with lower dose using A2NTX.","null","null","2014-02-01","Toxicon","Toxicon","Vol.81","null","32","36","eng","true","null","scientific_journal","null","null","10.1016/j.toxicon.2013.12.012","1879-3150","null","null","null","null","null" "Reversibility of ischemic findings on 3-tesla magnetic resonance T2(*)-weighted image after recanalization","Reversibility of ischemic findings on 3-tesla magnetic resonance T2(*)-weighted image after recanalization","Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","Nobuaki Yamamoto, Yuka Terasawa, Junichiro Satomi, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Shinji Nagahiro, Ryuji Kaji","null","Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.","Ischemic vessel signs (IVS) can be detected on 3-tesla T2(*)-weighted magnetic resonance images as a vessel enlargement at the territory of acute ischemia caused by major vessel occlusion or stenosis. Here, we studied changes in IVS before and after recanalization by the administration of intravenous recombinant tissue plasminogen activator (IV rtPA), carotid artery stenting or percutaneous transluminal angioplasty in patients with major vessel occlusion or stenosis. We performed magnetic resonance imaging for all patients treated by IV rtPA at the time of admission, shortly after and 24-72 hours after treatment with IV rtPA. We reviewed the IVS to assess its natural course of IVS by assessing patients who did not recanalize. IVS tended to disappear after recanalization. Conversely, in patients without recanalization, IVS did not disappear shortly after IV rtPA; rather, it disappeared 24-72 hours after IV rtPA, especially in the presence of complete infarction. Recanalization by IV rtPA or endovascular treatment contributed to improved clinical deficits or the prevention from further progression. IVS can be a parameter of misery perfusion and an important factor to detect the patients who have an indication of treatment for recanalization.","null","null","2014-02","The Journal of Medical Investigation : JMI","The Journal of Medical Investigation : JMI","Vol.61","No.1,2","190","196","eng","true","null","scientific_journal","null","null","10.2152/jmi.61.190","1349-6867","null","null","null","null","null" "Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation","Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation","Masaki Kamada, Yuishin Izumi, T Ayaki, Masataka Nakamura, Seiko Kagawa, Eiji Kudo, Wataru Sako, Hirofumi Maruyama, Y Nishida, Hideshi Kawakami, Hidefumi Ito, Ryuji Kaji","Masaki Kamada, Yuishin Izumi, T Ayaki, Masataka Nakamura, Seiko Kagawa, Eiji Kudo, Wataru Sako, Hirofumi Maruyama, Y Nishida, Hideshi Kawakami, Hidefumi Ito, Ryuji Kaji","null","We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.","We performed clinicopathological analyses of two amyotrophic lateral sclerosis (ALS) patients with homozygous Q398X optineurin (OPTN) mutation. Clinically, both patients presented signs of upper and lower motor neuron degeneration, but only Patient 1 showed gradual frontal dysfunction and extrapyramidal signs, and temporal lobe and motor cortex atrophy. Neuropathological examination of Patient 1 revealed extensive cortical and spinal motor neuron degeneration and widespread degeneration of the basal ganglia. Bilateral corticospinal tracts exhibited degeneration. Loss of spinal anterior horn cells (AHCs) and gliosis were observed, whereas posterior columns, Clarke's columns, intermediate lateral columns, and the Onuf's nucleus were spared. In the brainstem, moderate neuronal loss and gliosis were noted in the hypoglossal and facial motor nuclei. No Bunina bodies were found in the surviving spinal and brainstem motor neurons. Transactivation response (TAR) DNA-binding protein 43 (TDP-43)-positive neuronal and glial cytoplasmic inclusions were observed throughout the central nervous system. The Golgi apparatus in motor neurons of the brainstem and spinal cord was often fragmented. Immunoreactivity for OPTN was not observed in the brain and spinal cord, consistent with nonsense-mediated mRNA decay of OPTN. The TDP-43 pathology of Q398X was similar to that of an autosomal dominant E478G mutation. This result suggests that the loss-of-function, but not the proteinopathy itself, of OPTN results in TDP-43 deposits in neuronal and glial cytoplasm and Golgi apparatus fragmentation, leading to multisystem neurodegeneration.","null","null","2014-02","Neuropathology","Neuropathology","Vol.34","No.1","64","70","eng","true","null","scientific_journal","null","null","10.1111/neup.12051","1440-1789","null","null","null","null","null" "Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation.","Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation.","Wataru Sako, Yoshimichi Miyazaki, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Yoshimichi Miyazaki, Yuishin Izumi, Ryuji Kaji","null","The effect of GPi DBS was similar to STN DBS except for depression, however, only three studies described depression as adverse events. We need additional randomised trials with direct comparison between targets based on unified scoring of adverse events.","The effect of GPi DBS was similar to STN DBS except for depression, however, only three studies described depression as adverse events. We need additional randomised trials with direct comparison between targets based on unified scoring of adverse events.","null","null","2014-01-20","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","Vol.85","No.9","982","986","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2013-306090","1468-330X","null","null","null","null","null" "Brush sign on 3-T t2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy","Brush sign on 3-T t2*-weighted MRI as a potential predictor of hemorrhagic transformation after tissue plasminogen activator therapy","Yuka Terasawa, Nobuaki Yamamoto, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Junichiro Satomi, Masafumi Harada, Shinji Nagahiro, Ryuji Kaji","Yuka Terasawa, Nobuaki Yamamoto, Ryoma Morigaki, Koji Fujita, Yuishin Izumi, Junichiro Satomi, Masafumi Harada, Shinji Nagahiro, Ryuji Kaji","null","The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively (P=0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P=0.027). A good outcome (mRS, 0-1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group (P=0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4-59.8; P=0.022) was independently associated with hemorrhagic transformation. BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.","The brush sign (BS) is the enlargement of medullary veins on 3-T T2*-weighted MRI seen in patients with ischemic stroke because of major cerebral artery occlusion. However, the clinical relevance of BS in patients with acute stroke remains unclear. We assessed the correlation between detecting BS with the development of hemorrhagic transformation after intravenous thrombolysis. We enrolled consecutive patients with M1 or M2 occlusion treated with intravenous tissue plasminogen activator. We classified the patients into 2 groups: the group positive for BS (P-BS) and the group negative for BS (N-BS). We investigated the differences in MRI findings and the clinical outcome between the 2 groups. The subjects consisted of 36 patients (19 men; mean age, 74.7 years). Twenty-one patients (58%) had M1 occlusion, and 15 (42%) had M2 occlusion. Twenty-five patients (69%) were classified into the P-BS group and 11 (31%) into the N-BS group. Recanalization was observed in 15 (60%) and 10 (90%) patients in the P-BS and N-BS groups, respectively (P=0.116). Hemorrhagic transformation on MRI was observed more frequently in the P-BS group than in the N-BS group (64% versus 18%; P=0.027). A good outcome (mRS, 0-1) at discharge was found in 24% of patients in the P-BS group and in 45% of patients in the N-BS group (P=0.152). A multivariate logistic regression analysis revealed that the presence of BS (odds ratio, 9.08; 95% confidence interval, 1.4-59.8; P=0.022) was independently associated with hemorrhagic transformation. BS may predict the development of hemorrhagic transformation in patients with acute stroke treated with intravenous tissue plasminogen activator.","null","null","2014-01","Stroke","Stroke","Vol.45","No.1","274","276","eng","true","null","scientific_journal","null","null","10.1161/STROKEAHA.113.002640","1524-4628","null","null","null","null","null" "Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia.","Exome sequencing reveals a novel MRE11 mutation in a patient with progressive myoclonic ataxia.","Ryosuke Miyamoto, Hiroyuki Morino, Akio Yoshizawa, Yoshimichi Miyazaki, Hirofumi Maruyama, Nagahisa Murakami, Kei Fukada, Yuishin Izumi, Shinya Matsuura, Ryuji Kaji, Hideshi Kawakami","Ryosuke Miyamoto, Hiroyuki Morino, Akio Yoshizawa, Yoshimichi Miyazaki, Hirofumi Maruyama, Nagahisa Murakami, Kei Fukada, Yuishin Izumi, Shinya Matsuura, Ryuji Kaji, Hideshi Kawakami","null","Progressive myoclonic ataxia (PMA) is a clinical syndrome defined as progressive ataxia and myoclonus and infrequent seizures in the absence of progressive dementia. Due to the extremely heterogeneous nature of PMA, a large proportion of PMA cases remain molecularly undiagnosed. The aim of this study was to clarify the molecular etiology of PMA. The patient was a 52-year-old female from consanguineous parents. She developed a jerking neck movement at age 9, which gradually expanded to her entire body. On physical examination at age 47, she exhibited generalized, spontaneous myoclonus that occurred continuously. She also presented with mild limb and truncal ataxia. An electroencephalogram revealed no abnormalities. A brain MRI displayed no atrophy of the cerebellum. Electrophysiological studies suggested myoclonus of a subcortical origin. For further evaluation, we performed exome sequencing, and we identified a novel homozygous missense mutation in the MRE11 gene (NM_005590:c.140C>T:p.A47V). Subsequently, we analyzed the expression of MRE11 and related proteins (RAD50 and NBS1) via Western blot, and they were markedly decreased compared to a healthy control. Mutations in the MRE11 gene have been known to cause an ataxia-telangiectasia-like (ATLD) disorder. Accumulating evidence has indicated that its wide phenotypic variations in ATLD correspond to genotypic differences. Interestingly, our case exhibited a relatively mild decrease in NBS1 compared to previously reported cases of a homozygous missense mutation, which may account for the milder phenotype in this patient. Moreover, together with a recently reported case of an MRE11 mutation, it is suggested that MRE11 mutations can present as PMA.","Progressive myoclonic ataxia (PMA) is a clinical syndrome defined as progressive ataxia and myoclonus and infrequent seizures in the absence of progressive dementia. Due to the extremely heterogeneous nature of PMA, a large proportion of PMA cases remain molecularly undiagnosed. The aim of this study was to clarify the molecular etiology of PMA. The patient was a 52-year-old female from consanguineous parents. She developed a jerking neck movement at age 9, which gradually expanded to her entire body. On physical examination at age 47, she exhibited generalized, spontaneous myoclonus that occurred continuously. She also presented with mild limb and truncal ataxia. An electroencephalogram revealed no abnormalities. A brain MRI displayed no atrophy of the cerebellum. Electrophysiological studies suggested myoclonus of a subcortical origin. For further evaluation, we performed exome sequencing, and we identified a novel homozygous missense mutation in the MRE11 gene (NM_005590:c.140C>T:p.A47V). Subsequently, we analyzed the expression of MRE11 and related proteins (RAD50 and NBS1) via Western blot, and they were markedly decreased compared to a healthy control. Mutations in the MRE11 gene have been known to cause an ataxia-telangiectasia-like (ATLD) disorder. Accumulating evidence has indicated that its wide phenotypic variations in ATLD correspond to genotypic differences. Interestingly, our case exhibited a relatively mild decrease in NBS1 compared to previously reported cases of a homozygous missense mutation, which may account for the milder phenotype in this patient. Moreover, together with a recently reported case of an MRE11 mutation, it is suggested that MRE11 mutations can present as PMA.","null","null","2013-12-01","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.337","No.1-2","219","223","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2013.11.032","1878-5883","null","null","null","null","null" "Increased interleukin-17 in the cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease: a case-control study of rapidly progressive dementia","Increased interleukin-17 in the cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease: a case-control study of rapidly progressive dementia","Koji Fujita, Naoko Matsui, Yukitoshi Takahashi, Yasushi Iwasaki, Mari Yoshida, Tatsuhiko Yuasa, Yuishin Izumi, Ryuji Kaji","Koji Fujita, Naoko Matsui, Yukitoshi Takahashi, Yasushi Iwasaki, Mari Yoshida, Tatsuhiko Yuasa, Yuishin Izumi, Ryuji Kaji","null","Inflammatory responses in the cerebrospinal fluid (CSF) of patients with sporadic Creutzfeldt-Jakob disease (sCJD) remain elusive. We conducted a case-control study, in which 14 patients with sCJD, 14 with noninflammatory neurological disorders, and 14 with autoimmune encephalitis were enrolled. We used the suspension array system to measure the concentrations of 27 cytokines in CSF. The cytokine titers of the three groups were compared, and the correlation between the relevant cytokine titers and clinical parameters was investigated in the patients with sCJD. Levels of the two cytokines interleukin (IL)-1 receptor antagonist and IL-17 were significantly elevated in the patients with sCJD compared with those in the patients with noninflammatory neurological disorders: IL-17 levels in sCJD were approximately ten times higher than in the noninflammatory neurological disorders (mean, 35.46 vs. 3.45 pg/ml; P < 0.001) but comparable to that in encephalitis (mean, 32.16 pg/ml). In contrast, levels of classical proinflammatory cytokines such as IL-12(p70) and tumor necrosis factor-α were increased only in encephalitis. Although not significant, IL-17 titers tended to be higher in the patients with shorter disease duration before CSF sampling (r = -0.452; P = 0.104) and in those with lower CSF total protein concentrations (r = -0.473; P = 0.086). IL-17 is significantly increased in CSF in sCJD, which can be an early event in the pathogenesis of sCJD.","Inflammatory responses in the cerebrospinal fluid (CSF) of patients with sporadic Creutzfeldt-Jakob disease (sCJD) remain elusive. We conducted a case-control study, in which 14 patients with sCJD, 14 with noninflammatory neurological disorders, and 14 with autoimmune encephalitis were enrolled. We used the suspension array system to measure the concentrations of 27 cytokines in CSF. The cytokine titers of the three groups were compared, and the correlation between the relevant cytokine titers and clinical parameters was investigated in the patients with sCJD. Levels of the two cytokines interleukin (IL)-1 receptor antagonist and IL-17 were significantly elevated in the patients with sCJD compared with those in the patients with noninflammatory neurological disorders: IL-17 levels in sCJD were approximately ten times higher than in the noninflammatory neurological disorders (mean, 35.46 vs. 3.45 pg/ml; P < 0.001) but comparable to that in encephalitis (mean, 32.16 pg/ml). In contrast, levels of classical proinflammatory cytokines such as IL-12(p70) and tumor necrosis factor-α were increased only in encephalitis. Although not significant, IL-17 titers tended to be higher in the patients with shorter disease duration before CSF sampling (r = -0.452; P = 0.104) and in those with lower CSF total protein concentrations (r = -0.473; P = 0.086). IL-17 is significantly increased in CSF in sCJD, which can be an early event in the pathogenesis of sCJD.","null","null","2013-11-13","Journal of Neuroinflammation","Journal of Neuroinflammation","Vol.10","null","135","135","eng","true","null","scientific_journal","null","null","10.1186/1742-2094-10-135","1742-2094","null","null","null","null","null" "Increasing and persistent DWI changes in a patient with Hereditary Diffuse Leukoencephalopathy with Spheroids.","Increasing and persistent DWI changes in a patient with Hereditary Diffuse Leukoencephalopathy with Spheroids.","Yuka Terasawa, Yusuke Osaki, Toshitaka Kawarai, Tatsurou Sugimoto, Antonio Orlacchio, Takashi Abe, Yuishin Izumi, Ryuji Kaji","Yuka Terasawa, Yusuke Osaki, Toshitaka Kawarai, Tatsurou Sugimoto, Antonio Orlacchio, Takashi Abe, Yuishin Izumi, Ryuji Kaji","null","We report a case with genetically confirmed hereditary diffuse leukoencephalopathy with spheroids with distinctive MRI features. A 52-year-old woman with a family history of juvenile dementia presented with an 18-month history of progressive cognitive decline. Longitudinal magnetic resonance imaging studies of the brain revealed increasing and persistent white matter hyperintensities on diffusion-weighted images. Linear high intensity signal along axonal fibers arisen from the cerebral cortex was also shown. Finding of subcortical calcifications was noted on brain CT scan. Sequence analysis of CSF1R showed a novel missense mutation c.2467C>T (p.Ala823Val). Persistent and increasing diffusion on magnetic resonance image, presumably reflecting intramyelinic oedema in regions of neurodegeneration, is a distinctive feature observed in this case. The presence of this unique finding can be a diagnostic clue in the early stage of the disease.","We report a case with genetically confirmed hereditary diffuse leukoencephalopathy with spheroids with distinctive MRI features. A 52-year-old woman with a family history of juvenile dementia presented with an 18-month history of progressive cognitive decline. Longitudinal magnetic resonance imaging studies of the brain revealed increasing and persistent white matter hyperintensities on diffusion-weighted images. Linear high intensity signal along axonal fibers arisen from the cerebral cortex was also shown. Finding of subcortical calcifications was noted on brain CT scan. Sequence analysis of CSF1R showed a novel missense mutation c.2467C>T (p.Ala823Val). Persistent and increasing diffusion on magnetic resonance image, presumably reflecting intramyelinic oedema in regions of neurodegeneration, is a distinctive feature observed in this case. The presence of this unique finding can be a diagnostic clue in the early stage of the disease.","null","null","2013-08-30","Journal of the Neurological Sciences","Journal of the Neurological Sciences","null","null","null","null","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2013.08.027","1878-5883","null","null","null","null","null" "Successful treatment of stiff person syndrome with sequential use of tacrolimus","Successful treatment of stiff person syndrome with sequential use of tacrolimus","Syunya Nakane, Koji Fujita, Yoshiko Shibuta, Naoko Matsui, Masafumi Harada, Ryo Urushihara, Yoshihiko Nishida, Yuishin Izumi, Ryuji Kaji","Syunya Nakane, Koji Fujita, Yoshiko Shibuta, Naoko Matsui, Masafumi Harada, Ryo Urushihara, Yoshihiko Nishida, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2013-05-28","Journal of Neurology, Neurosurgery, and Psychiatry","Journal of Neurology, Neurosurgery, and Psychiatry","Vol.84","No.10","1177","1180","eng","true","null","scientific_journal","null","null","10.1136/jnnp-2013-305425","1468-330X","null","null","null","null","null" "Oromandibular dystonia associated with SCA36","Oromandibular dystonia associated with SCA36","Miyashiro Ai, Sugihara Katsunobu, Toshitaka Kawarai, Miyamoto Ryosuke, Yuishin Izumi, Morino Hiroyuki, Maruyama Hirofumi, Orlacchio Antonio, Kawakami Hideshi, Ryuji Kaji","Miyashiro Ai, Sugihara Katsunobu, Toshitaka Kawarai, Miyamoto Ryosuke, Yuishin Izumi, Morino Hiroyuki, Maruyama Hirofumi, Orlacchio Antonio, Kawakami Hideshi, Ryuji Kaji","null","null","null","null","null","2013-04","Movement Disorders","Movement Disorders","Vol.28","No.4","558","559","eng","true","null","scientific_journal","null","null","10.1002/mds.25304","1531-8257","null","null","null","null","null" "Application of long-range polymerase chain reaction in the diagnosis of X-linked dystonia-parkinsonism","Application of long-range polymerase chain reaction in the diagnosis of X-linked dystonia-parkinsonism","Toshitaka Kawarai, Pasco Matthew D. Paul, Teleg A. Rosalia, Masaki Kamada, Sakai Waka, Komei Shimozono, Makoto Mizuguchi, Tabuena Daisy, Orlacchio Antonio, Yuishin Izumi, Satoshi Goto, Lee V. Lillian, Ryuji Kaji","Toshitaka Kawarai, Pasco Matthew D. Paul, Teleg A. Rosalia, Masaki Kamada, Sakai Waka, Komei Shimozono, Makoto Mizuguchi, Tabuena Daisy, Orlacchio Antonio, Yuishin Izumi, Satoshi Goto, Lee V. Lillian, Ryuji Kaji","null","null","null","null","null","2013-03","Neurogenetics","Neurogenetics","Vol.14","No.2","167","169","eng","true","null","scientific_journal","null","null","10.1007/s10048-013-0357-x","1364-6753","null","null","null","null","null" "Basal ganglia hyperintensity on T1-weighted imaging of a patient with central nervous system metastasis producing carcinoembryonic antigens","Basal ganglia hyperintensity on T1-weighted imaging of a patient with central nervous system metastasis producing carcinoembryonic antigens","Koji Fujita, W Sakai, Masafumi Harada, Mika Sakaki, Hideo Mure, Shinji Nagahiro, Yuishin Izumi, Ryuji Kaji","Koji Fujita, W Sakai, Masafumi Harada, Mika Sakaki, Hideo Mure, Shinji Nagahiro, Yuishin Izumi, Ryuji Kaji","null","We herein report unusual basal ganglia hyperintense lesions on noncontrast T1-weighted magnetic resonance imaging in a patient with central nervous system metastasis from lung adenocarcinoma that was treated with gefitinib. T2*-weighted magnetic resonance imaging showed no hypointense lesions, thereby excluding the possibility of calcification or haemorrhage. A stereotactic brain biopsy of the left basal ganglia lesions revealed atypical cells, some of which formed a glandular lumen with a micropapillary pattern. These cells were immunopositive for markers of lung adenocarcinoma, thereby confirming the diagnosis of metastasis. We speculate that proteins, including carcinoembryonic antigens from the adenocarcinoma cells in the basal ganglia, may have contributed to the hyperintensity observed on noncontrast T1-weighted magnetic resonance imaging.","We herein report unusual basal ganglia hyperintense lesions on noncontrast T1-weighted magnetic resonance imaging in a patient with central nervous system metastasis from lung adenocarcinoma that was treated with gefitinib. T2*-weighted magnetic resonance imaging showed no hypointense lesions, thereby excluding the possibility of calcification or haemorrhage. A stereotactic brain biopsy of the left basal ganglia lesions revealed atypical cells, some of which formed a glandular lumen with a micropapillary pattern. These cells were immunopositive for markers of lung adenocarcinoma, thereby confirming the diagnosis of metastasis. We speculate that proteins, including carcinoembryonic antigens from the adenocarcinoma cells in the basal ganglia, may have contributed to the hyperintensity observed on noncontrast T1-weighted magnetic resonance imaging.","null","null","2013-02-01","Internal Medicine","Internal Medicine","Vol.52","No.3","381","383","eng","true","null","scientific_journal","null","null","10.2169/internalmedicine.52.8835","1349-7235","null","null","null","null","null" "Diagnostic spectrum of multifocal motor neuropathy","Diagnostic spectrum of multifocal motor neuropathy","Naoko Matsui, Ai Miyashiro, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kuwabara, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Mezaki, Jun Kawamata, Takefumi Hitomi, Tomihiro Imai, Nobuo Kohara, Kimiyoshi Arimura, Kokichi Arisawa, Susumu Kusunoki, Ryuji Kaji","Naoko Matsui, Ai Miyashiro, Yoshimitsu Shimatani, Hiroyuki Nodera, Yuishin Izumi, Satoshi Kuwabara, Masayuki Baba, Tetsuo Komori, Masahiro Sonoo, Takahiro Mezaki, Jun Kawamata, Takefumi Hitomi, Tomihiro Imai, Nobuo Kohara, Kimiyoshi Arimura, Kokichi Arisawa, Susumu Kusunoki, Ryuji Kaji","null","null","null","null","null","2013","Clinical & Experimental Neuroimmunology","Clinical & Experimental Neuroimmunology","Vol.4","No.2","210","215","eng","true","null","scientific_journal","null","null","10.1111/cen3.12025","1759-1961","null","null","null","null","null" "The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement.","The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement.","Hiroyuki Ishiura, Wataru Sako, Mari Yoshida, Toshitaka Kawarai, Osamu Tanabe, Jun Goto, Yuji Takahashi, Hidetoshi Date, Jun Mitsui, Budrul Ahsan, Yaeko Ichikawa, Atsushi Iwata, Hiide Yoshino, Yuishin Izumi, Koji Fujita, Kouji Maeda, Satoshi Goto, Hidetaka Koizumi, Ryoma Morigaki, Masako Ikemura, Naoko Yamauchi, Shigeo Murayama, A Garth Nicholson, Hidefumi Ito, Gen Sobue, Masanori Nakagawa, Ryuji Kaji, Shoji Tsuji","Hiroyuki Ishiura, Wataru Sako, Mari Yoshida, Toshitaka Kawarai, Osamu Tanabe, Jun Goto, Yuji Takahashi, Hidetoshi Date, Jun Mitsui, Budrul Ahsan, Yaeko Ichikawa, Atsushi Iwata, Hiide Yoshino, Yuishin Izumi, Koji Fujita, Kouji Maeda, Satoshi Goto, Hidetaka Koizumi, Ryoma Morigaki, Masako Ikemura, Naoko Yamauchi, Shigeo Murayama, A Garth Nicholson, Hidefumi Ito, Gen Sobue, Masanori Nakagawa, Ryuji Kaji, Shoji Tsuji","null","Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal-dominant neurodegenerative disorder characterized by widespread fasciculations, proximal-predominant muscle weakness, and atrophy followed by distal sensory involvement. To date, large families affected by HMSN-P have been reported from two different regions in Japan. Linkage and haplotype analyses of two previously reported families and two new families with the use of high-density SNP arrays further defined the minimum candidate region of 3.3 Mb in chromosomal region 3q12. Exome sequencing showed an identical c.854C>T (p.Pro285Leu) mutation in the TRK-fused gene (TFG) in the four families. Detailed haplotype analysis suggested two independent origins of the mutation. Pathological studies of an autopsied patient revealed TFG- and ubiquitin-immunopositive cytoplasmic inclusions in the spinal and cortical motor neurons. Fragmentation of the Golgi apparatus, a frequent finding in amyotrophic lateral sclerosis, was also observed in the motor neurons with inclusion bodies. Moreover, TAR DNA-binding protein 43 kDa (TDP-43)-positive cytoplasmic inclusions were also demonstrated. In cultured cells expressing mutant TFG, cytoplasmic aggregation of TDP-43 was demonstrated. These findings indicate that formation of TFG-containing cytoplasmic inclusions and concomitant mislocalization of TDP-43 underlie motor neuron degeneration in HMSN-P. Pathological overlap of proteinopathies involving TFG and TDP-43 highlights a new pathway leading to motor neuron degeneration.","Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal-dominant neurodegenerative disorder characterized by widespread fasciculations, proximal-predominant muscle weakness, and atrophy followed by distal sensory involvement. To date, large families affected by HMSN-P have been reported from two different regions in Japan. Linkage and haplotype analyses of two previously reported families and two new families with the use of high-density SNP arrays further defined the minimum candidate region of 3.3 Mb in chromosomal region 3q12. Exome sequencing showed an identical c.854C>T (p.Pro285Leu) mutation in the TRK-fused gene (TFG) in the four families. Detailed haplotype analysis suggested two independent origins of the mutation. Pathological studies of an autopsied patient revealed TFG- and ubiquitin-immunopositive cytoplasmic inclusions in the spinal and cortical motor neurons. Fragmentation of the Golgi apparatus, a frequent finding in amyotrophic lateral sclerosis, was also observed in the motor neurons with inclusion bodies. Moreover, TAR DNA-binding protein 43 kDa (TDP-43)-positive cytoplasmic inclusions were also demonstrated. In cultured cells expressing mutant TFG, cytoplasmic aggregation of TDP-43 was demonstrated. These findings indicate that formation of TFG-containing cytoplasmic inclusions and concomitant mislocalization of TDP-43 underlie motor neuron degeneration in HMSN-P. Pathological overlap of proteinopathies involving TFG and TDP-43 highlights a new pathway leading to motor neuron degeneration.","null","null","2012-08-10","American Journal of Human Genetics","American Journal of Human Genetics","Vol.91","No.2","320","329","eng","true","null","scientific_journal","null","null","10.1016/j.ajhg.2012.07.014","1537-6605","null","null","null","null","null" "Broad spectrum of dystonia associated with a novel thanatosis-associated protein domain-containing apoptosis-associated protein 1 mutation in a Japanese family with dystonia 6, torsion.","Broad spectrum of dystonia associated with a novel thanatosis-associated protein domain-containing apoptosis-associated protein 1 mutation in a Japanese family with dystonia 6, torsion.","Ryosuke Miyamoto, Etsuro Ohta, Toshitaka Kawarai, Hidetaka Koizumi, Wataru Sako, Yuishin Izumi, Fumiya Obata, Ryuji Kaji","Ryosuke Miyamoto, Etsuro Ohta, Toshitaka Kawarai, Hidetaka Koizumi, Wataru Sako, Yuishin Izumi, Fumiya Obata, Ryuji Kaji","null","null","null","null","null","2012-07-20","Movement Disorders","Movement Disorders","Vol.27","No.10","1324","1325","eng","true","null","scientific_journal","null","null","10.1002/mds.25106","1531-8257","null","null","null","null","null" "Antibodies to N-methyl-D-aspartate glutamate receptors in Creutzfeldt-Jakob disease patients.","Antibodies to N-methyl-D-aspartate glutamate receptors in Creutzfeldt-Jakob disease patients.","Koji Fujita, Tatsuhiko Yuasa, Yukitoshi Takahashi, Keiko Tanaka, Wataru Sako, Hidetaka Koizumi, Yasushi Iwasaki, Mari Yoshida, Yuishin Izumi, Ryuji Kaji","Koji Fujita, Tatsuhiko Yuasa, Yukitoshi Takahashi, Keiko Tanaka, Wataru Sako, Hidetaka Koizumi, Yasushi Iwasaki, Mari Yoshida, Yuishin Izumi, Ryuji Kaji","null","Psychiatric symptom can be a prominent feature early in Creutzfeldt-Jakob disease (CJD), which is also common in autoantibody-mediated limbic encephalitis. We hypothesized that anti-neuronal autoantibodies, especially those against N-methyl-D-aspartate glutamate receptors (NMDAR), can also be associated with CJD. Thirteen patients with CJD and 13 patients with limbic encephalitis were enrolled. Immunohistochemistry demonstrated that serum of CJD patients reacted with neuronal components of the rat hippocampus, indicating that those samples contained anti-neuronal antibodies. Enzyme-linked immunosorbent assay revealed that titers of antibodies against peptides of GluN2B subunit of NMDAR were significantly elevated in the serum and cerebrospinal fluid of CJD patients.","Psychiatric symptom can be a prominent feature early in Creutzfeldt-Jakob disease (CJD), which is also common in autoantibody-mediated limbic encephalitis. We hypothesized that anti-neuronal autoantibodies, especially those against N-methyl-D-aspartate glutamate receptors (NMDAR), can also be associated with CJD. Thirteen patients with CJD and 13 patients with limbic encephalitis were enrolled. Immunohistochemistry demonstrated that serum of CJD patients reacted with neuronal components of the rat hippocampus, indicating that those samples contained anti-neuronal antibodies. Enzyme-linked immunosorbent assay revealed that titers of antibodies against peptides of GluN2B subunit of NMDAR were significantly elevated in the serum and cerebrospinal fluid of CJD patients.","null","null","2012-07-17","Journal of Neuroimmunology","Journal of Neuroimmunology","Vol.251","No.1-2","90","93","eng","true","null","scientific_journal","null","null","10.1016/j.jneuroim.2012.06.010","1872-8421","null","null","null","null","null" "Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis.","Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis.","Kotaro Ogaki, Yuanzhe Li, Naoki Atsuta, Hiroyuki Tomiyama, Manabu Funayama, Hazuki Watanabe, Ryoichi Nakamura, Hideo Yoshino, Seiji Yato, Asako Tamura, Yutaka Naito, Akira Taniguchi, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Nobutaka Hattori, Gen Sobue","Kotaro Ogaki, Yuanzhe Li, Naoki Atsuta, Hiroyuki Tomiyama, Manabu Funayama, Hazuki Watanabe, Ryoichi Nakamura, Hideo Yoshino, Seiji Yato, Asako Tamura, Yutaka Naito, Akira Taniguchi, Koji Fujita, Yuishin Izumi, Ryuji Kaji, Nobutaka Hattori, Gen Sobue","null","Recently, a hexanucleotide repeat expansion in C9orf72 was identified as the most common cause of both sporadic and familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Western populations. We analyzed 563 Japanese patients with ALS (552 sporadic and 11 familial) using fluorescent fragment-length analysis of C9orf72 and repeat-primed polymerase chain reaction analysis. Haplotype analysis was performed for 42 single nucleotide polymorphisms in patients with C9orf72 repeat expansion. C9orf72 repeat expansion was found in 2 patients with sporadic ALS (2/552 = 0.4%) and no patients with familial ALS (0/11 = 0%). In the probands' families, 1 primary progressive aphasia patient and 1 asymptomatic 76-year-old individual exhibited C9orf72 repeat expansion. All of the patients with the C9orf72 repeat expansion carried the 20-single nucleotide polymorphism consensus risk haplotype. The frequency of the C9orf72 repeat expansion among Japanese patients is much lower than in Western populations. The existence of a 76-year-old asymptomatic carrier supported the notion of incomplete penetrance. The C9orf72 mutation should be analyzed in sporadic ALS patients after determining their family histories not only of frontotemporal dementia but also of primary progressive aphasia.","Recently, a hexanucleotide repeat expansion in C9orf72 was identified as the most common cause of both sporadic and familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Western populations. We analyzed 563 Japanese patients with ALS (552 sporadic and 11 familial) using fluorescent fragment-length analysis of C9orf72 and repeat-primed polymerase chain reaction analysis. Haplotype analysis was performed for 42 single nucleotide polymorphisms in patients with C9orf72 repeat expansion. C9orf72 repeat expansion was found in 2 patients with sporadic ALS (2/552 = 0.4%) and no patients with familial ALS (0/11 = 0%). In the probands' families, 1 primary progressive aphasia patient and 1 asymptomatic 76-year-old individual exhibited C9orf72 repeat expansion. All of the patients with the C9orf72 repeat expansion carried the 20-single nucleotide polymorphism consensus risk haplotype. The frequency of the C9orf72 repeat expansion among Japanese patients is much lower than in Western populations. The existence of a 76-year-old asymptomatic carrier supported the notion of incomplete penetrance. The C9orf72 mutation should be analyzed in sporadic ALS patients after determining their family histories not only of frontotemporal dementia but also of primary progressive aphasia.","null","null","2012-06-21","Neurobiology of Aging","Neurobiology of Aging","Vol.33","No.10","2527.e11","6","eng","true","null","scientific_journal","null","null","10.1016/j.neurobiolaging.2012.05.011","1558-1497","null","null","null","null","null" "Generalized dystonia in a patient with a novel mutation in the GLUD1 gene","Generalized dystonia in a patient with a novel mutation in the GLUD1 gene","Ryosuke Miyamoto, Satoshi Goto, Wataru Sako, Ai Miyashiro, Isabelle Kim, Fabienne Escande, Masafumi Harada, Ryoma Morigaki, Koutaro Asanuma, Yoshifumi Mizobuchi, Shinji Nagahiro, Yuishin Izumi, Ryuji Kaji","Ryosuke Miyamoto, Satoshi Goto, Wataru Sako, Ai Miyashiro, Isabelle Kim, Fabienne Escande, Masafumi Harada, Ryoma Morigaki, Koutaro Asanuma, Yoshifumi Mizobuchi, Shinji Nagahiro, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2012-06-21","Movement Disorders","Movement Disorders","Vol.27","No.9","1198","1199","eng","true","null","scientific_journal","null","null","10.1002/mds.25081","1531-8257","null","null","null","null","null" "Early detection of familial Creutzfeldt-Jakob disease on diffusion-weighted imaging before symptom onset.","Early detection of familial Creutzfeldt-Jakob disease on diffusion-weighted imaging before symptom onset.","Yuka Terasawa, Koji Fujita, Yuishin Izumi, Ryuji Kaji","Yuka Terasawa, Koji Fujita, Yuishin Izumi, Ryuji Kaji","null","Familial Creutzfeldt-Jakob disease (CJD) with V180I shows different clinical characteristics from classical CJD and is difficult to diagnose in the early stage. We report a CJD180 patient in whom results of diffusion-weighted imaging (DWI) led us to suspect CJD before symptoms started. A 68-year-old woman presented to our hospital with headache and nausea and underwent magnetic resonance imaging. DWI showed cortical hyperintensity. Three months later, cognitive function started to decline and CJD180 was diagnosed following genetic examination. In the early stage, ADC values were not decreased and single positron emission computed tomography demonstrated a decreased pattern like Alzheimer disease.","Familial Creutzfeldt-Jakob disease (CJD) with V180I shows different clinical characteristics from classical CJD and is difficult to diagnose in the early stage. We report a CJD180 patient in whom results of diffusion-weighted imaging (DWI) led us to suspect CJD before symptoms started. A 68-year-old woman presented to our hospital with headache and nausea and underwent magnetic resonance imaging. DWI showed cortical hyperintensity. Three months later, cognitive function started to decline and CJD180 was diagnosed following genetic examination. In the early stage, ADC values were not decreased and single positron emission computed tomography demonstrated a decreased pattern like Alzheimer disease.","null","null","2012-05-27","Journal of the Neurological Sciences","Journal of the Neurological Sciences","Vol.319","No.1-2","130","132","eng","true","null","scientific_journal","null","null","10.1016/j.jns.2012.04.004","1878-5883","null","null","null","null","null" "Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease.","Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease.","Koji Fujita, Tatsuhiko Yuasa, Osamu Watanabe, Yukitoshi Takahashi, Shuji Hashiguchi, Katsuhito Adachi, Yuishin Izumi, Ryuji Kaji","Koji Fujita, Tatsuhiko Yuasa, Osamu Watanabe, Yukitoshi Takahashi, Shuji Hashiguchi, Katsuhito Adachi, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2012-05-26","Journal of Neurology","Journal of Neurology","Vol.259","No.10","2249","2250","eng","true","null","scientific_journal","null","null","10.1007/s00415-012-6554-y","1432-1459","null","null","null","null","null" "Efficacy of zolpidem for dystonia: a study among different subtypes","Efficacy of zolpidem for dystonia: a study among different subtypes","Yoshimichi Miyazaki, Wataru Sako, Koutaro Asanuma, Yuishin Izumi, T Miki, Ryuji Kaji","Yoshimichi Miyazaki, Wataru Sako, Koutaro Asanuma, Yuishin Izumi, T Miki, Ryuji Kaji","null","Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5-20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician's. Drowsiness was the dose-limiting factor.","Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5-20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician's. Drowsiness was the dose-limiting factor.","null","null","2012-04-17","Frontiers in Neurology","Frontiers in Neurology","Vol.3","No.58","null","null","eng","true","null","scientific_journal","null","null","10.3389/fneur.2012.00058","1664-2295","null","null","null","null","null" "Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential","Parkin interacts with Klokin1 for mitochondrial import and maintenance of membrane potential","Yukiko Kuroda, Wataru Sako, Satoshi Goto, Tomoyo Sawada, Daisuke Uchida, Yuishin Izumi, Tetsuya Takahashi, Noriko Kagawa, Masayasu Matsumoto, Mitsuru Matsumoto, Ryosuke Takahashi, Ryuji Kaji, Takao Mitsui","Yukiko Kuroda, Wataru Sako, Satoshi Goto, Tomoyo Sawada, Daisuke Uchida, Yuishin Izumi, Tetsuya Takahashi, Noriko Kagawa, Masayasu Matsumoto, Mitsuru Matsumoto, Ryosuke Takahashi, Ryuji Kaji, Takao Mitsui","null","Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and that Klokin 1 may compensate for Parkin deficiency.","Parkin is a multifunctional protein, including maintaining mitochondrial homeostasis. Recent evidence suggests that Parkin is recruited from the cytoplasm to damaged mitochondria with low membrane potential. We found that intracellular localization of Parkin changed with cellular growth phase. Parkin was preferentially localized in the mitochondria of cultured cells. The mitochondria with large amounts of Parkin showed preserved membrane potentials even during treatment with carbonyl cyanide m-chlorophenylhydrazone. Here we report a novel protein named Klokin 1 that transports Parkin to the mitochondria. Klokin 1 was localized to the mitochondria and enhanced mitochondrial expression of Parkin. Klokin 1 enhanced cell viability in Parkin-silenced cells. Klokin 1 expression was enhanced in the brains of Parkin-deficient mice but not in an autopsied PARK2 brain. Our findings indicate that mitochondrial Parkin prevents mitochondrial depolarization and that Klokin 1 may compensate for Parkin deficiency.","null","null","2012-03-01","Human Molecular Genetics","Human Molecular Genetics","Vol.21","No.5","991","1003","eng","true","null","scientific_journal","null","null","10.1093/hmg/ddr530","1460-2083","null","null","null","null","null" "Nuclear factor B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations","Nuclear factor B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations","Wataru Sako, Hidefumi Ito, Mari Yoshida, Hidetaka Koizumi, Masaki Kamada, Koji Fujita, Yoshio Hashizume, Yuishin Izumi, Ryuji Kaji","Wataru Sako, Hidefumi Ito, Mari Yoshida, Hidetaka Koizumi, Masaki Kamada, Koji Fujita, Yoshio Hashizume, Yuishin Izumi, Ryuji Kaji","null","Nuclear factor κ B (NF-κB) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-κB in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-κB were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-κB was altered when compared to that of NC; NF-κB immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-κB in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-κB might be lost immediately after its activation. The microglial induction of NF-κB might contribute to neuroinflammation. In conclusion, NF-κB signaling pathway could have a key role in the pathomechanism of ALS.","Nuclear factor κ B (NF-κB) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-κB in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-κB were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-κB was altered when compared to that of NC; NF-κB immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-κB in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-κB might be lost immediately after its activation. The microglial induction of NF-κB might contribute to neuroinflammation. In conclusion, NF-κB signaling pathway could have a key role in the pathomechanism of ALS.","null","null","2011-11","Clinical Neuropathology","Clinical Neuropathology","Vol.31","No.6","418","423","eng","true","null","scientific_journal","null","null","10.5414/NP300493","0722-5091","null","null","null","null","null" "行政的な「高次脳機能障害」の診断","Diagnostic criteria of the administrative higher brain dysfunction","和泉 唯信, 中村 和己, 永廣 信治","Yuishin Izumi, 中村 和己, Shinji Nagahiro","null","Diagnostic criteria of the administrative higher brain dysfunction are defined. Young people between the period of entering school and starting work occasionally suffer from brain damage. Although the patient may seem to recover, memory and attention disturbances may continue. As a result, higher brain dysfunction may interfere with return to school, and reinstatement is difficult.Patients diagnosed with higher brain dysfunction by these diagnostic criteria can continue rehabilitation and achieve functional restoration. In the Tokushima University Hospital, many patients with cerebrovascular disease, brain tumor, or traffic injury(in that order)consulted about higher brain dysfunction.","Diagnostic criteria of the administrative higher brain dysfunction are defined. Young people between the period of entering school and starting work occasionally suffer from brain damage. Although the patient may seem to recover, memory and attention disturbances may continue. As a result, higher brain dysfunction may interfere with return to school, and reinstatement is difficult.Patients diagnosed with higher brain dysfunction by these diagnostic criteria can continue rehabilitation and achieve functional restoration. In the Tokushima University Hospital, many patients with cerebrovascular disease, brain tumor, or traffic injury(in that order)consulted about higher brain dysfunction.","null","null","2011-04-25","四国医学雑誌","Shikoku Acta Medica","Vol.67","null","29","34","jpn","true","null","scientific_journal","null","null","null","0037-3699","null","http://repo.lib.tokushima-u.ac.jp/110349","null","null","null" "筋エコーにより筋炎の関与が判明した右房拡張症の一例","A case of enlargement of the right atrium associated with myositis detected by muscle ultrasonography","宮﨑 由道, 高松 直子, 宮城 愛, 寺澤 由佳, 松井 尚子, 浅沼 光太郎, 和泉 唯信, 梶 龍兒","Yoshimichi Miyazaki, 高松 直子, Ai Miyashiro, Yuka Terasawa, Naoko Matsui, Koutaro Asanuma, Yuishin Izumi, Ryuji Kaji","null","症例は45歳女性で,全身倦怠感を主訴にした.42歳時に動悸症状を自覚し,44歳時に全身倦怠感を強く自覚し,近医の心電図で心房細動を指摘された.聴診では心雑音や過剰心音はなく,肺音は清,頸動脈雑音を認めなかった.頸部,四肢近位部にごく軽度の筋力低下を認め,Gowers徴候は明らかでなかった.24時間心電図検査で頻発する発作性心房細動を認め,モニター心電図で最大約7秒の洞停止を確認した.心エコーでは右房の著明な拡張,左房の軽度拡張を認めた.三尖弁に軽度逆流を認めたが,逆流の程度からは右房拡張の直接原因とは考え難かった.僧帽弁に異常は認めず,左室収縮能は保たれていた.膠原病関連疾患としての筋炎,サルコイドーシスなどの鑑別目的に筋エコー検査を施行した.特発性右房拡張症中に,全身性筋炎を伴う心筋炎を原因とした一群の存在の可能性があり,スクリーニング検査として,筋エコー検査は侵襲性が少なく,簡便で,またペースメーカー導入後も使用でき有用であった.","A 45-year-old woman was admitted to the hospital because of general malaise since 2005. She have not remarkable disease in the past history. In the family history, one of her older sister died of ulcerative colitis, another one suffers from systemic lupus erythematosis, and her older brother affected of Behçet's disease. On electrocardiogram examination, atrial fibrillation was revealed associated with remarkable dilation of the right atrium in echocardiogram, but any abnormal finding is not seen both ventricles. The ultrasonographic findings of the biceps brachi showed remarkable myopathic pattern. A biopsy specimen obtained from the biceps brachi, these muscles revealed degeneration and necrosis of muscle fibers, interstitial infiltration with monocytes, and perivascular infiltrates of inflammatory cells. In the magnetic resonance imaging of the heart showed, not only remarkable dilatation of right atria, but also diffuse high intensity areas in left ventricle under T2-intensified conditions. We diagnosed generalized myositis involved with myocarditis, and treated with steroid. One year later, she still takes steroid, and her symptoms improvement continuously.If one of cardiac atrium or ventricle enlarged, there is possibility of the cardiac myositis or systemic myositis. In these cases, skeletal muscle ultrasonography may be non-invasive and useful method of differential diagnosis.","null","null","2011-04","神経超音波医学","Neurosonology","Vol.24","No.1","12","14","jpn","true","null","scientific_journal","null","null","10.2301/neurosonology.24.12","0917-074X","null","http://search.jamas.or.jp/link/ui/2012112946","null","null","null" "Temporal evolution of sporadic Creutzfeldt-Jakob disease monitored by 3-Tesla MR spectroscopy.","Temporal evolution of sporadic Creutzfeldt-Jakob disease monitored by 3-Tesla MR spectroscopy.","Koji Fujita, Masafumi Harada, Tatsuhiko Yuasa, Makoto Sasaki, Yuishin Izumi, Ryuji Kaji","Koji Fujita, Masafumi Harada, Tatsuhiko Yuasa, Makoto Sasaki, Yuishin Izumi, Ryuji Kaji","null","null","null","null","null","2011-02-17","Journal of Neurology","Journal of Neurology","Vol.258","No.7","1368","1370","eng","true","null","scientific_journal","null","null","10.1007/s00415-011-5939-7","1432-1459","null","null","null","null","null" "Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T2*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator","Incidence and clinical correlation of intracranial hemorrhages observed by 3-tesla gradient echo T2*-weighted images following intravenous thrombolysis with recombinant tissue plasminogen activator","Masafumi Harada, Naomi Morita, Masaaki Uno, Junichiro Satomi, Yuishin Izumi, Koutaro Asanuma, Hiromu Nishitani, Ryuji Kaji, Shinji Nagahiro","Masafumi Harada, Naomi Morita, Masaaki Uno, Junichiro Satomi, Yuishin Izumi, Koutaro Asanuma, Hiromu Nishitani, Ryuji Kaji, Shinji Nagahiro","null","The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.","The purpose of this study was to determine the incidence and clinical correlation of intracranial hemorrhages (ICHs) detected by 3-tesla gradient echo T(2)*-weighted images after intravenous recombinant tissue plasminogen activator (rt-PA) administration. We included 43 consecutive patients with anterior-circulation ischemia who underwent MRI studies before and after thrombolysis. Each hemorrhage was classified as a hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) according to the European Cooperative Acute Stroke Study definition. The clinical outcome was defined as an improvement (> or =4-point reduction) or deterioration (> or =4-point increase) based on a comparison between the initial and the 30-day NIHSS scores. The incidence of ICHs was 58%, and the HI rate was 52%; both were higher than the rates reported in the literature. Most of the patients with HI improved clinically, and these patients had second MRAs that showed recanalization. None of the patients with PH demonstrated improvement. Three-tesla MRI may reveal a higher frequency of HI type hemorrhages than lower-field MRIs, and HI may be a predictor of good recovery by reflecting the presence of recanalization. The rate of PH in our study was low compared to other studies, probably due to the lower dosage of rt-PA.","null","null","2010-04-08","Cerebrovascular Diseases","Cerebrovascular Diseases","Vol.29","No.6","571","575","eng","true","null","scientific_journal","null","null","10.1159/000306644","1421-9786","null","null","null","null","null" "Neurological manifestations in hereditary hemorrhagic telangiectasia type 1: a familial case in Japan","Neurological manifestations in hereditary hemorrhagic telangiectasia type 1: a familial case in Japan","Naoko Matsui, Yuishin Izumi, Hiroyuki Azuma, Ryuji Kaji","Naoko Matsui, Yuishin Izumi, Hiroyuki Azuma, Ryuji Kaji","null","null","null","null","null","2010-01","Journal of Tokushima National Hospital","Journal of Tokushima National Hospital","Vol.2010","No.1","11","14","eng","true","null","scientific_journal","null","null","null","2185-3169","null","http://ci.nii.ac.jp/naid/40019066124/","null","null","null" "脳死様状態を呈したGuillain-Barre症候群の1例","脳死様状態を呈したGuillain-Barre症候群の1例","宮﨑 由道, 向井 洋平, 浅沼 光太郎, 和泉 唯信, 梶 龍兒","Yoshimichi Miyazaki, 向井 洋平, Koutaro Asanuma, Yuishin Izumi, Ryuji Kaji","null","脳死様状態を呈した劇症型GBSの症例を救命しえた.GBSの中に,急性に脳死様状態を呈し,α昏睡をきたす劇症型GBSの一群の存在が示唆された.脳死様状態を呈する劇症型GBSでは死亡症例も多く,厳重な全身管理が必要である.(著者抄録)","脳死様状態を呈した劇症型GBSの症例を救命しえた.GBSの中に,急性に脳死様状態を呈し,α昏睡をきたす劇症型GBSの一群の存在が示唆された.脳死様状態を呈する劇症型GBSでは死亡症例も多く,厳重な全身管理が必要である.(著者抄録)","null","null","2010","臨床脳波","Clinical Electroencephalography","Vol.52","No.2","123","125","jpn","true","null","scientific_journal","null","null","null","0485-1447","null","null","null","null","null" "A case of cryptococcal meningitis successfully treated with liposomal amphotericin-B, Fulcytosine, and Voriconazole","A case of cryptococcal meningitis successfully treated with liposomal amphotericin-B, Fulcytosine, and Voriconazole","Yoshimichi Miyazaki, Ai Miyashiro, Yoshimitsu Simatani, Naoko Matsui, Koutaro Asanuma, Yuishin Izumi, Ryuji Kaji","Yoshimichi Miyazaki, Ai Miyashiro, Yoshimitsu Simatani, Naoko Matsui, Koutaro Asanuma, Yuishin Izumi, Ryuji Kaji","null","クリプトコッカス性髄膜炎の59歳男性症例について検討した.発熱と頭痛を主訴とし,風邪と診断さたが,嘔吐,意識障害,歩行困難の症状が出現し,発症から16日目に入院となった.入院時に意識障害と強い傾眠傾向が認められた.右眼の対光反射が鈍く,瞳孔径の左右差が認められた.顕著な頸部硬直も認められた.ウイルス関連抗原抗体は陰性であった.脳脊髄液はキサントクロミーを呈しており,脳脊髄液圧,脳脊髄液中の細胞数と蛋白濃度の上昇,脳脊髄液中の糖濃度低下が認められた.May-Giemsa染色および墨汁染色では莢膜を有する菌体が多数確認された.Cryptococcus抗原の256倍上昇が示された.頭部のガドリニウム造影MRI検査で脳溝に沿った造影像を認めた.クリプトコッカス性髄膜炎と診断し,liposomal amphotericin-Bおよびfulcytosineによる2剤療法を開始した.臨床検査結果および脳脊髄液検査結果は徐々に改善したが,入院45日目に左顔面麻痺が出現した.MRI検査から新しい病変が確認され,造影MRI検査で造影病変の拡大を認めた.Voriconazole追加による3剤療法を開始した.脳脊髄液検査結果および臨床症状の改善を示し,入院180日目に退院となった.左顔面麻痺も徐々に改善した.","クリプトコッカス性髄膜炎の59歳男性症例について検討した.発熱と頭痛を主訴とし,風邪と診断さたが,嘔吐,意識障害,歩行困難の症状が出現し,発症から16日目に入院となった.入院時に意識障害と強い傾眠傾向が認められた.右眼の対光反射が鈍く,瞳孔径の左右差が認められた.顕著な頸部硬直も認められた.ウイルス関連抗原抗体は陰性であった.脳脊髄液はキサントクロミーを呈しており,脳脊髄液圧,脳脊髄液中の細胞数と蛋白濃度の上昇,脳脊髄液中の糖濃度低下が認められた.May-Giemsa染色および墨汁染色では莢膜を有する菌体が多数確認された.Cryptococcus抗原の256倍上昇が示された.頭部のガドリニウム造影MRI検査で脳溝に沿った造影像を認めた.クリプトコッカス性髄膜炎と診断し,liposomal amphotericin-Bおよびfulcytosineによる2剤療法を開始した.臨床検査結果および脳脊髄液検査結果は徐々に改善したが,入院45日目に左顔面麻痺が出現した.MRI検査から新しい病変が確認され,造影MRI検査で造影病変の拡大を認めた.Voriconazole追加による3剤療法を開始した.脳脊髄液検査結果および臨床症状の改善を示し,入院180日目に退院となった.左顔面麻痺も徐々に改善した.","null","null","2010","Journal of Tokushima National Hospital","Journal of Tokushima National Hospital","Vol.1","null","31","34","eng","true","null","scientific_journal","null","null","null","2185-3169","null","null","null","null","null" "Stroke MRIと血栓溶解療法","Stroke MRIと血栓溶解療法","宇野 昌明, 森田 奈緒美, 原田 雅史, 和泉 唯信, 中根 俊成, 永廣 信治","Masaaki Uno, Naomi Morita, Masafumi Harada, Yuishin Izumi, Shunya Nakane, Shinji Nagahiro","null","null","null","null","null","2008-05","脳と循環","脳と循環","Vol.13","No.2","125","132","jpn","true","null","scientific_journal","null","null","null","null","null","null","null","null","null" "徳島大学病院stroke centerでの脳卒中医療の現状 -特にstroke MRIの有用性-","Diagnosis and Treatment in Stroke Center of Tokushima University Hospital : Efficacy of 3 Tesla Stroke MRI(