Faculty Profiles - TAKASHIMA Hiroshi

Chikada Ayaka, Orimo Kenta, Mitsui Jun, Matsukawa Takashi, Ishiura Hiroyuki, Toda Tatsushi, Mizusawa Hidehiro, Takahashi Yuji, Katsuno Masahisa, Hara Kazuhiro, Onodera Osamu, Ishihara Tomohiko, Tada Masayoshi, Kuwabara Satoshi, Sugiyama Atsuhiko, Yamanaka Yoshitaka, Takahashi Ryosuke, Sawamoto Nobukatsu, Sakato Yusuke, Ishimoto Tomoyuki, Hanajima Ritsuko, Watanabe Yasuhiro, Takigawa Hiroshi, Adachi Tadashi, Abe Koji, Yamashita Toru, Takashima Hiroshi, Higashi Keiko, Kira Junichi, Yabe Ichiro, Matsushima Masaaki, Ogata Katsuhisa, Ishikawa Kinya, Nishida Yoichiro, Ishiguro Taro, Ozaki Kokoro, Nagata Tetsuya, Tsuji Shoji . 日本のMSAレジストリ　多系統萎縮症の多施設コホート研究(The Japan MSA registry: A multicenter cohort study of multiple system atrophy) . Neurology and Clinical Neuroscience12 ( 5 ) 271 - 277 2024.9

Language：English Publisher：(一社)日本神経学会

多系統萎縮症(MSA)レジストリを構築し、MSA患者の臨床的および疫学的特徴を評価した。本研究には13施設が参加した。臨床イベントの発生について、神経科医が12ヵ月毎の患者来院時にUMSARSパート2スコアを用いて、また看護師が6ヵ月毎に電話でUMSARSパート1スコアを用いて前向きに評価した。患者329例を解析した。小脳型(MSA-C)は216例、パーキンソン型(MSA-P)は113例で、症状発症時の平均年齢は58.2±8.9歳、登録時の症状の平均持続期間は3.5±2.2年であった。12ヵ月時点での脱落率はそれぞれ15.8%と48.6%、12ヵ月時点のUMSARSパート1スコアおよびパート2スコアの変化量はそれぞれ平均7.9±5.6点と6.4±5.9点であった。本レジストリでは遺伝子解析を行っていたため、COQ2変異を有する患者を対象とした臨床試験参加者の募集に役立った。臨床情報と生体標本はバイオバンクに保管された。以上より、MSA-CはMSAの約65%、MSA-Pは約35%で、脱落率を抑えるには電話によるインタビューが重要なことが示唆された。

Ito Miwa, Sugiyama Atsuhiko, Higuchi Yujiro, Takashima Hiroshi, Takahashi Yuji, Mizusawa Hidehiro, Kuwabara Satoshi . Writer's Cramps as an Initial Symptom of Spinocerebellar Ataxia Type 14 . Internal Medicine63 ( 15 ) 2183 - 2186 2024.8

Language：English Publisher：The Japanese Society of Internal Medicine

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxia caused by mutations in PRKCG. We herein report a case of SCA14 presenting with writer's cramp that predated the onset of progressive ataxia by four years. A 47-year-old Japanese woman had an 11-year history of writer's cramps, followed by unsteadiness. Whole-exome sequencing revealed a heterozygous mutation in PRKCG (p.C142S), leading to an SCA14 diagnosis. Therefore, writer's cramp might be a characteristic extracerebellar sign of SCA14 and can precede the onset of cerebellar ataxia.

DOI： 10.2169/internalmedicine.2943-23

Language：English Publisher：(一社)日本内科学会

症例は47歳女性で、36歳時に緩徐進行性の筆記困難と不安定歩行を認めた。患者の母親は47歳時に脊髄小脳変性症と診断されていた。脳神経検査は正常であったが、円滑性追跡眼球運動は衝動性眼球運動により中断され、軽度の小脳性構音障害を認めた。運動検査では、筆記中の右手姿位が正常でなく、右親指手関節の過屈曲が認められた。深部腱反射および感覚系は正常であった。指追跡試験における右手のジストニア姿勢を伴う軽度ジスメトリア、踵脛試験における下肢協調不全も認められた。歩行は不安定で、タンデム歩行障害を認めた。表面筋電図検査では、筆記中に右長母指屈筋が長母指伸筋と共収縮することが明らかとなった。脳MRIで小脳萎縮が認められた。全エクソームシーケンシングで、PRKCG遺伝子のヘテロ接合体変異(p.C142S)が判明し、脊髄小脳失調症14型と診断した。同変異は患者の母親にも認められた。トリヘキシフェニジルとクロナゼパムによる治療を行った。その結果、軽度の改善が認められた。

Tanaka M., Takenouchi N., Arishima S., Matsuzaki T., Nozuma S., Matsuura E., Takashima H., Kubota R. . HLA-A*24 Increases the Risk of HTLV-1-Associated Myelopathy despite Reducing HTLV-1 Proviral Load . International Journal of Molecular Sciences25 ( 13 ) 2024.7

Language：Japanese Publisher：International Journal of Molecular Sciences

Increased human T-cell leukemia virus type 1 (HTLV-1) proviral load (PVL) is a significant risk factor for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is controversy surrounding whether HTLV-1-specific cytotoxic T lymphocytes (CTLs) are beneficial or harmful to HAM/TSP patients. Recently, HTLV-1 Tax 301–309 has been identified as an immunodominant epitope restricted to HLA-A*2402. We investigated whether HLA-A*24 reduces HTLV-1 PVL and the risk of HAM/TSP using blood samples from 152 HAM/TSP patients and 155 asymptomatic HTLV-1 carriers. The allele frequency of HLA-A*24 was higher in HAM/TSP patients than in asymptomatic HTLV-1 carriers (72.4% vs. 58.7%, odds ratio 1.84), and HLA-A*24-positive patients showed a 42% reduction in HTLV-1 PVL compared to negative patients. Furthermore, the PVL negatively correlated with the frequency of Tax 301–309-specific CTLs. These findings are opposite to the effects of HLA-A*02, which reduces HTLV-1 PVL and the risk of HAM/TSP. Therefore, we compared the functions of CTLs specific to Tax 11–19 or Tax 301–309, which are immunodominant epitopes restricted to HLA-A*0201 or HLA-A*2402, respectively. The maximum responses of these CTLs were not different in the production of IFN-γ and MIP-1β or in the expression of CD107a—a marker for the degranulation of cytotoxic molecules. However, Tax 301–309-specific CTLs demonstrated 50-fold higher T-cell avidity than Tax 11–19-specific CTLs, suggesting better antigen recognition at low expression levels of the antigens. These findings suggest that HLA-A*24, which induces sensitive HTLV-1-specific CTLs, increases the risk of HAM/TSP despite reducing HTLV-1 PVL.

DOI： 10.3390/ijms25136858

Kojima F., Okamoto Y., Ando M., Higuchi Y., Hobara T., Yuan J., Yoshimura A., Hashiguchi A., Matsuura E., Takashima H. . A novel homozygous HPDL variant in Japanese siblings with autosomal recessive hereditary spastic paraplegia: case report and literature review . Neurogenetics25 ( 2 ) 149 - 156 2024.4

Language：Japanese Publisher：Neurogenetics

Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.Gly114Cys), in the HPDL gene in two siblings with autosomal recessive hereditary spastic paraplegia (HSP). Despite sharing the same likely pathogenic variant, the older sister had pure HSP, whereas her brother had severe and complicated HSP, accompanied by early-onset mental retardation and abnormalities in magnetic resonance imaging. Given the clinical heterogeneity and potential for treatable conditions in HPDL-related diseases, we emphasize the importance of genetic testing for the HPDL gene.

DOI： 10.1007/s10048-024-00746-y

Yoshimoto Yukiyo, Yoshimoto Shoko, Kakiuchi Kensuke, Miyagawa Rumina, Ota Shin, Hosokawa Takafumi, Ishida Shimon, Higuchi Yujiro, Hashiguchi Akihiro, Takashima Hiroshi, Arawaka Shigeki . 新規GJB1変異を伴うX連鎖性シャルコー・マリー・トゥース病における中枢神経系病変の空間的変動(Spatial Fluctuation of Central Nervous System Lesions in X-linked Charcot-Marie-Tooth Disease with a Novel GJB1 Mutation) . Internal Medicine63 ( 4 ) 571 - 576 2024.2

Language：English Publisher：(一社)日本内科学会

症例は25歳男性で、7歳時に初回発作が出現し、頭部MRIのT2強調画像で頭頂葉と後頭葉の両側脳白質および脳梁膨大部に高信号域を認めた。13歳時に2回目の発作が出現し、MRIの拡散強調画像とT2強調画像で脳梁と頭頂葉の白質に高信号域を認めた。現症の発作では、歩行中に感覚障害と構音障害が出現し、地域病院に入院した。翌日に症状が悪化し、右上下肢の軽度筋力低下も認めたため、搬送されてきた。神経学的検査で見当識障害と右片麻痺が判明し、腱反射が完全に消失し、下肢の振動覚が低下していた。凹足も認めた。家族歴の聴取から、症例の弟がシャルコー・マリー・トゥース病(CMT)と診断されており、症例の母親が下垂足を有していることが判明した。DNA解析を行い、新規のギャップ結合β1(GJB1)変異(c.169C>T、p.Gln57*)が特定された。症例の母親と弟も同様の変異を有していたことから、新規GJB1変異を伴うX連鎖性CMT 1型と診断した。2週後の追跡MRIでは、拡散強調画像における白質の高信号域が消失し、脳梁膨大部に高信号域が出現していた。5ヵ月後、膨大部病変は完全に消失した。

Nozuma S., Yoshimura A., Pai S.C., Chen H.J., Matsuura E., Tanaka M., Kodama D., Dozono M., Matsuzaki T., Takashima H., Yang Y.C., Kubota R. . Geographic characteristics of HTLV-1 molecular subgroups and genetic substitutions in East Asia: Insights from complete genome sequencing of HTLV-1 strains isolated in Taiwan and Japan . PLoS Neglected Tropical Diseases18 ( 2 ) e0011928 2024.2

Language：Japanese Publisher：PLoS Neglected Tropical Diseases

Background Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in sur-rounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration. Methodology/Principal findings The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations. In total, 15/26 (58%) isolates from Taiwan belonged to the transcontinental subgroup and 11/26 (42%) isolates belonged to the Japanese subgroup. The transcontinental subgroup was significantly more prevalent among Taiwanese isolates than Japanese isolates (58% vs 18%, P < 0.0001). The mutation rate for the complete HTLV-1 sequence was as low as 0.2%. On examining individual base substitutions, the G-to-A mutation was predominant. Bayesian phylogenetic tree analysis estimated the time to the most recent common ancestor for the transcontinental and Japanese subgroups to be 28447 years. The transcontinental subgroups from Taiwan and Japan appeared to form clusters according to their respective regions.Conclusions/Significance The transcontinental subgroup of HTLV-1 is predominant in Taiwan, while the Japanese subgroup is common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup.

DOI： 10.1371/journal.pntd.0011928

Takahiro Hobara, Masahiro Ando, Yujiro Higuchi, Jun-Hui Yuan, Akiko Yoshimura, Fumikazu Kojima, Yutaka Noguchi, Jun Takei, Yu Hiramatsu, Satoshi Nozuma, Tomonori Nakamura, Tadashi Adachi, Keiko Toyooka, Toru Yamashita, Yusuke Sakiyama, Akihiro Hashiguchi, Eiji Matsuura, Yuji Okamoto, Hiroshi Takashima . Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy. . Journal of neurology, neurosurgery, and psychiatry96 ( 2 ) 140 - 149 2024Reviewed International journal

Language：Japanese Publishing type：Research paper (scientific journal)

BACKGROUND: The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions. METHODS: We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in LRP12, GIPC1 and RILPL1 genes was conducted using PCR and long-read sequencing technologies. RESULTS: We identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with LRP12-oculopharyngodistal myopathy (p<0.0001). Additionally, GIPC1 and RILPL1 repeat expansions were absent in our IPN cases. CONCLUSION: We initially elucidate LRP12 repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.

DOI： 10.1136/jnnp-2024-333403

Hamada Y., Matsuoka H., Sato S., Kawabata Y., Iwamoto K., Ikeda M., Sato T., Takaguchi G., Takashima H. . Combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter for M2 occlusions: the ONE-SEG technique . Frontiers in Neurology15 1424030 2024

Language：Japanese Publisher：Frontiers in Neurology

Background: Endovascular therapy (EVT) for distal medium vessel occlusions requires prioritizing effectiveness and safety. We developed a technique combining the deployment of only the distal basket segment of the EMBOTRAP III and an aspiration catheter (AC) for M2 occlusions, called the “ONE-SEG technique,” and evaluated its clinical and technical impacts. Methods: This was a retrospective review of 30 consecutive patients with M2 segment middle cerebral artery occlusion treated using the ONE-SEG technique. This method involves deploying the EMBOTRAP III through a microcatheter in only one segment and guiding the AC to the M2 origin or distal M1. The rates of final-pass expanded thrombolysis in cerebral infarction (eTICI) scores of 2c/3 or 2b/2c/3, safety (symptomatic intracranial hemorrhage [sICH]), and clinical outcomes (modified Rankin Scale [mRS] score 0–2, 0–3 at 90 days, and mortality at 90 days) were evaluated. Results: Of the 30 cases, 36.7% were female, and the mean age was 75.6 ± 11.0 years. The ONE-SEG technique was used for 17 cases (56.7%, median NIHSS 10 [5–15.5]) with primary M2 occlusion and 13 cases (43.3%, median NIHSS 20 [14–22.5]) with secondary M2 occlusion after proximal thrombus removal. The successful final reperfusion rate (eTICI 2b/2c/3) was 90% overall (27/30 cases). One case (3.3%) developed sICH with secondary M2 occlusion. At 3 months, mRS scores 0–2 were seen in 64.7% of patients with primary M2 occlusion (11/17 cases) and in 23.1% (3/13 cases) with secondary M2 occlusion. Conclusion: EVT using the ONE-SEG technique appears to be safe and effective for M2 occlusion.

DOI： 10.3389/fneur.2024.1424030

Kakumoto T., Orimo K., Matsukawa T., Mitsui J., Ishihara T., Onodera O., Suzuki Y., Morishita S., Tsuji S., Nagata T., Ozaki K., Ishiguro T., Nishida Y., Ishikawa K., Ogata K., Matsushima M., Yabe I., Kira J., Higashi K., Takashima H., Adachi T., Takigawa H., Watanabe Y., Hanajima R., Sawamoto N., Ishimoto T., Sakato Y., Takahashi R., Yamanaka Y., Sugiyama A., Kuwabara S., Tada M., Hara K., Katsuno M., Takahashi Y., Mizusawa H., Yamashita T., Abe K., Ishiura H., Toda T., Chikada A. . Frequency of FGF14 intronic GAA repeat expansion in patients with multiple system atrophy and undiagnosed ataxia in the Japanese population . European Journal of Human Genetics33 ( 3 ) 325 - 333 2024

Language：Japanese Publisher：European Journal of Human Genetics

Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous system dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar ataxia type 27B (SCA27B), a late-onset ataxia with an autosomal dominant inheritance. Patients with SCA27B may also exhibit autonomic nervous system dysfunction, potentially overlapping with the clinical presentations of MSA patients. In this study, to explore the possible involvement of expanded GAA repeats in MSA, we investigated the frequencies of expanded GAA repeats in FGF14 in 548 patients with MSA, 476 patients with undiagnosed ataxia, and 455 healthy individuals. To fully characterize the structures of the expanded GAA repeats, long-range PCR products suggesting the expansion of GAA repeats were further analyzed using a long-read sequencer. Of the 548 Japanese MSA patients, we identified one MSA patient (0.2%) carrying an expanded repeat with (GAA)≥250. Among the 476 individuals with undiagnosed ataxia, (GAA)≥250 was observed in six (1.3%); this frequency was higher than that in healthy individuals (0.2%). The clinical characteristics of the MSA patient with (GAA)≥250 were consistent with those of MSA, but not with SCA27B. Further research is warranted to explore the possibility of the potential association of expanded GAA repeats in FGF14 with MSA.

DOI： 10.1038/s41431-024-01743-3

Takashima Hiroshi . Brain localization of functional disorders including hysterical symptoms from the perspective of higher brain functions : A new neural anatomy and motor physiological model . Neurological Therapeutics41 ( 4 ) 634 - 641 2024

Language：Japanese Publisher：Japanese Society of Neurological Therapeutics

Hysterical symptoms, commonly referred to as functional neurological disorder, encompass various neurological manifestations not explainable by current neurology frameworks, suggesting involvement of psychogenic mechanisms. On the other hand, advances in neurophysiological anatomy have revealed that beyond the traditionally identified primary motor cortex (pyramidal tract), once regarded as the final output pathway, other essential output pathways have been functionally verified, such as the cortico–reticulospinal tract. Currently, motor output from the brain to the spinal cord should be considered through dual pathways. In this review, we elucidate hysterical symptoms through the prospective of a new functional brain anatomy paradigm that integrates motor output with dual pathways. Most hysterical motor symptoms can be attributed to disorders affecting the premotor cortex and supplementary motor area–reticulospinal tract. Since this cortico–reticular spinal tract is bilaterally innervated, symptoms arise from bilateral brain lesions. Bilateral abnormalities within this pathway are frequently identified through techniques such as 123I–IMP–SPECT or diffusion tensor imaging. In addition, the function of the reticular formation is considered to correlate with symptoms observed in PNES (psychogenic non–epileptic seizure), including impaired consciousness, tonic seizures of internal muscles, abnormalities in blood pressure and breathing, hypersensitivity to sound and light, as well as hyperalgesia. The origin of hysterical symptoms is primarily attributed to disorders involving the reticular formation and cortico–reticulospinal tract, caused by bilateral diffuse brain damage. Most hysterical symptoms could be explained through adept application of the new neurophysiological model, which delineates motor output into dual pathways. To comprehend complex brain symptoms, neurologists require an update of functional neurophysiological models.

DOI： 10.15082/jsnt.41.4_634

Nakahashi Takumi, Matsuura Ryuki, Kikuchi Kenjiro, Takeda Rikako, Takeuchi Hirokazu, Nonoyama Hazuki, Hirata Yuko, Koichihara Reiko, Hashiguchi Akihiro, Takashima Hiroshi, Hamano Shin-ichiro . A case of childhood Charcot-Marie-Tooth disease type 2A with nerve root enlargement in longitudinal evaluation of spinal MR neurography . NO TO HATTATSU56 ( 6 ) 427 - 431 2024

Language：Japanese Publisher：The Japanese Society of Child Neurology

A 7-years-old girl was admitted with the principal complaint of abnormal gait. She presented with distal muscle weakness, bilateral Achilles tendon reflex depression, and peripheral sensory disturbance. The results of the spinal cord magnetic resonance (MR) neurography were normal ; however, she had median nerve conduction disorders. As a genetic analysis revealed a mitofusin 2 mutation (c.718T＞G, p.F240V), she was diagnosed with Charcot-Marie-Tooth (CMT) type 2A. Despite continued physical therapy, her symptoms progressed slowly. At the age of 10 years and 4 months, she was unable to walk without support, and spinal MR neurography demonstrated bilateral nerve root enlargement in L2-5 regions. In children with CMT type 2A, the morphology of the spinal cord nerve root is not abnormal in the early stages, but nerve root enlargement may be observed as symptoms progress. Spinal MR neurography may be useful in evaluating disease activity.

DOI： 10.11251/ojjscn.56.427

HAMADA Yuki, MIYASHITA Fumio, MATSUOKA Hideki, NISHINAKAMA Yuki, KAI Yusuke, YAMASHITA Yusuke, IKEDA Mei, TAKAGUCHI Go, MASUDA Keisuke, KUBO Fumikatsu, TAKASHIMA Hiroshi . Alternative Proximal Protection Method during Carotid Artery Stenting Using Combined Transbrachial and Transradial Artery Approaches . NMC Case Report Journal10 ( 0 ) 273 - 278 2023.12

Language：English Publisher：The Japan Neurosurgical Society

Herein, we report a case of carotid artery stenting with proximal flow protection for severe stenosis of the left internal carotid artery using transbrachial and transradial artery approaches. Because an abdominal aortic aneurysm was present, we avoided the transfemoral approach. The procedure was successfully performed with a combination of an 8-Fr balloon guide catheter and microballoon catheter on separate axes. No complications such as pseudoaneurysm, thrombosis, or dissection were observed at the puncture site. The patient was discharged without complications and showed good outcomes at 3 months. This technique may offer a useful alternative for patients with severe stenosis who cannot be treated using a femoral artery approach.

DOI： 10.2176/jns-nmc.2023-0071

Matsuura E., Nozuma S., Shigehisa A., Dozono M., Nakamura T., Tanaka M., Kubota R., Hashiguchi A., Takashima H. . HTLV-1-associated myelopathy/tropical spastic paraplegia with sporadic late-onset nemaline myopathy: a case report . BMC Musculoskeletal Disorders24 ( 1 ) 355 2023.12

Language：Japanese Publisher：BMC Musculoskeletal Disorders

Background: Sporadic late onset nemaline myopathy (SLONM) is a muscle disorder characterized by the presence of nemaline rods in muscle fibers. SLONM has no known genetic cause but has been associated with monoclonal gammopathy of undetermined significance and with human immunodeficiency virus (HIV) infection. Human T-cell leukemia virus-1 (HTLV-1) is a known causative agent of adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraplegia (HAM/TSP), a chronic inflammatory neurological disease. HTLV-1 has been reported to be implicated in inflammatory myopathies, as well as in HIV infection.; however, there have been no reports of an association between HTLV-1 infection and SLONM to date. Case presentation: A 70-year-old Japanese woman presented with gait disturbance, lumbar kyphosis, and respiratory dysfunction. The diagnosis of HAM/TSP with SLONM was made based on characteristic clinical symptoms of HAM/TSP, such as spasticity in the lower extremities, and cerebrospinal fluid test results; and of SLONM, such as generalized head drooping, respiratory failure, and muscle biopsy results. Steroid treatment was initiated and improvement in her stooped posture was observed after 3 days of treatment. Conclusion: This is the first case report of SLONM combined with HTLV-1 infection. Further studies are needed to elucidate the relationship between retroviruses and muscle diseases.

DOI： 10.1186/s12891-023-06461-3

Hamada Yuki, Miyashita Fumio, Matsuoka Hideki, Nishinakama Yuki, Kai Yusuke, Yamashita Yusuke, Ikeda Mei, Takaguchi Go, Masuda Keisuke, Kubo Fumikatsu, Takashima Hiroshi . 経上腕動脈および経橈骨動脈アプローチを併用した頸動脈ステント留置術における代替的近位保護法(Alternative Proximal Protection Method during Carotid Artery Stenting Using Combined Transbrachial and Transradial Artery Approaches) . NMC Case Report Journal10 ( 1 ) 273 - 278 2023.12

Language：English Publisher：(一社)日本脳神経外科学会

症例は67歳男性。頸動脈超音波検査で左内頸動脈の高度狭窄が偶然発見され、当院を受診した。高血圧、脂質異常症、腹部大動脈、慢性閉塞性肺疾患の既往があった。経上腕動脈および経橈骨動脈アプローチを用いて、左内頸動脈の高度狭窄に対する近位フローを伴う頸動脈ステント留置術を施行した。術後合併症は認められず、超音波検査でもプラークの突出はみられなかった。頸動脈ステント留置術施行5日後のCT血管造影で、上腕動脈および橈骨動脈に異常はみられなかった。最終的にmodified Rankin scale(mRS)スコア0点で退院した。退院後3ヵ月もmRSは依然として0のままであった。

Arimura Yoshihiro, Sobue Gen, Hattori Naoki, Takashima Hiroshi, Harigai Masayoshi, Nagata Koichi, Makino Hirofumi . 慢性末梢神経障害が残存する顕微鏡的多発血管炎に対する免疫グロブリン静注療法　多施設無作為化二重盲検試験(Intravenous immunoglobulin for chronic residual peripheral neuropathy in microscopic polyangiitis: A multicentre randomised double-blind trial) . Modern Rheumatology33 ( 6 ) 1125 - 1136 2023.11

Language：English Publisher：Oxford University Press

顕微鏡的多発血管炎に伴うグルココルチコイド抵抗性神経障害を有する患者に対する免疫グロブリン静注療法(IVIg)の有効性と安全性を評価する目的で、第III相多施設無作為化二重盲検プラセボ対照並行群間比較試験を実施した。37例をIVIg群(19例)またはプラセボ群(18例)に割り付け、第1週および第5週にIVIgまたはプラセボ投与を5日間行い、第9週はIVIg群にプラセボ投与、プラセボ群にIVIgを行った。有効性解析対象は36例(それぞれ19例、17例)であった。8週後(第9週の治療開始前)における徒手筋力テストの合計スコア変化量(最小二乗平均値)は、IVIg群で9.02、プラセボ群で6.71(群間差2.32、95%CI -2.60～7.23、p=0.345)、4週後(第5週の治療開始前)ではそれぞれ6.81、2.83(同3.99、-1.22～9.19、p=0.129)であり、IVIgにより合計スコアは改善したものの両群間に有意差は認めなかった。IVIg群において安全性に関する新たな懸念は認めなかった。

Nozuma Satoshi, Yuji-Takeuchi Mika, Nakamura Tomonori, Saigo Ryuji, Masuda Mirai, Ando Masahiro, Sakiyama Yusuke, Miyata Ryo, Tabata Kazuhiro, Matsuura Eiji, Takashima Hiroshi . 外科的介入前の免疫療法により改善した重症腫瘍随伴性グルタミン酸脱炭酸酵素抗体スペクトラム障害の1例(A case of severe paraneoplastic glutamic acid decarboxylase antibody-spectrum disorder with improvement through prior immunotherapy before surgical intervention) . Clinical and Experimental Neuroimmunology14 ( 4 ) 202 - 206 2023.11

Language：English Publisher：(一社)日本神経免疫学会

症例は65歳女性で、高血圧の既往があった。めまいとふらつき歩行を初発症状として呈していた。嚥下障害や歩行障害が悪化したため、発症12ヵ月後に入院となった。各種検査の結果、小脳失調とスティッフパーソン症候群を重複するGAD抗体-スペクトル障害と診断された。外科的介入は不可能と判断され、免疫療法が開始された。メチルプレドニゾロン静注および免疫グロブリン静注を含む免疫療法が実施され、神経症状は著しく改善した。しかし、経口プレドニゾロン(PSL)漸減により構音障害および歩行失調の悪化が認められた。発症27ヵ月後に胸腔鏡下胸腺摘出術が施行された。神経学的症状はさらに改善し、PSL漸減に成功した。

Makito Hirano, Motoi Kuwahara, Yuko Yamagishi, Makoto Samukawa, Kanako Fujii, Shoko Yamashita, Masahiro Ando, Nobuyuki Oka, Mamoru Nagano, Taro Matsui, Toshihide Takeuchi, Kazumasa Saigoh, Susumu Kusunoki, Hiroshi Takashima, Yoshitaka Nagai . CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy. . Scientific reports13 ( 1 ) 17801 - 17801 2023.10International journal

Language：English Publishing type：Research paper (scientific journal)

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sjögren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barré syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barré syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary, we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy.

DOI： 10.1038/s41598-023-45011-8