Faculty Profiles - TAKASHIMA Hiroshi

Papers - TAKASHIMA Hiroshi

Division display 61 - 80 of about 319 ／ All the affair displays >>

Masayuki Wakita, Ran Takei, Fumio Miyashita, Yuki Hamada, Satoshi Ohyama, Hideki Matsuoka, Hiroshi Takashima . Carotid ultrasound features of anomalous left vertebral artery originating from the aortic arch proximal to the left subclavian artery . Neuroradiology Journal30 ( 2 ) 168 - 171 2017.4Reviewed International journal

Publisher：SAGE Publications Inc.

We present three cases of anomalous origin of the left vertebral artery (LVA) detected during the evaluation of stroke. The VA usually enters the transverse foramen of the sixth cervical vertebra (C6), but an anomalous LVA originating from the aorta frequently enters at a higher level. In our series, ultrasound of the LVA showed entry at C4 in two patients and at C5 in one patient. These findings suggested anomalous LVA origin, and three-dimensional computed tomography demonstrated the LVA arising from the aorta proximal to the left subclavian arteries. Carotid duplex ultrasound is useful for the diagnosis of this anomaly.

DOI： 10.1177/1971400916687585

Scopus

PubMed

Hideaki Nishihara, Masatoshi Omoto, Masaki Takao, Yujiro Higuchi, Michiaki Koga, Motoharu Kawai, Hiroo Kawano, Eiji Ikeda, Hiroshi Takashima, Takashi Kanda . Autopsy case of the C12orf65 mutation in a patient with signs of mitochondrial dysfunction. . Neurology. Genetics3 ( 4 ) e171 2017Reviewed International journal

Language：English

OBJECTIVE: To describe the autopsy case of a patient with a homozygous 2-base deletion, c171_172delGA (p.N58fs), in the C12orf65 gene. METHODS: We described the clinical history, neuroimaging data, neuropathology, and genetic analysis of the patients with C12orf65 mutations. RESULTS: The patient was a Japanese woman with a history of delayed psychomotor development, primary amenorrhea, and gait disturbance in her 20s. She was hospitalized because of respiratory failure at the age of 60. Pectus excavatum, long fingers and toes, and pes cavus were revealed by physical examination. Her IQ score was 44. Neurologic examination revealed ophthalmoplegia, optic atrophy, dysphagia, distal dominant muscle weakness and atrophy, hyperreflexia at patellar tendon reflex, hyporeflexia at Achilles tendon reflex, and extensor plantar reflexes. At age 60, she died of pneumonia. Lactate levels were elevated in the patient's serum and CSF. T2-weighted brain MRI showed symmetrical hyperintense brainstem lesions. At autopsy, axial sections exposed symmetrical cyst formation with brownish lesions in the upper spinal cord, ventral medulla, pons, dorsal midbrain, and medial hypothalamus. Microscopic analysis of these areas demonstrated mild gliosis with rarefaction. Cell bodies in the choroid plexuses were eosinophilic and swollen. Electron microscopic examination revealed that these cells contained numerous abnormal mitochondria. Whole-exome sequencing revealed the 2-base deletion in C12orf65. CONCLUSIONS: We report an autopsy case of the C12orf65 mutation, and findings suggest that mitochondrial dysfunction may underlie the unique clinical presentations.

DOI： 10.1212/NXG.0000000000000171

Scopus

PubMed

Takashima Hiroshi . Diagnostic tips and treatment of autoimmune encephalopathy . Neurological Therapeutics34 ( 3 ) 160 - 162 2017Reviewed

Authorship：Lead author Language：Japanese Publisher：Japanese Society of Neurological Therapeutics

Autoimmune encephalopathies are clinically and immunologically heterogeneous disorders. Many different types of autoimmune encephalopathy have been discovered, and most common type may be Hashimoto encephalopathy in it. In clinical situations, we often recognize that patients with autoimmune encephalopathy are often misdiagnosed as exhibiting functional psychogenic movement, conversion, or somatoform disorders. We clinically analyzed 63 patients with autoimmune encephalopathy. Two–thirds of patients showed motor disturbance mostly with give–way weakness. About 70% of patients showed sensory abnormalities such as strong pain, deep muscle pain, dysesthesia, paresthesia, or fast neurologic pain. Most pain was distributed in manner that was not explainable anatomically. 27% of patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. We observed memory loss, PNES (psychogenic non–epileptic seizure), dissociative amnesia, hyperventilation, opsoclonus, epilepsy, or autonomic symptoms amongst our patients. Although give–way weakness, anatomically unexplainable pain, and strange involuntary movements were thought to be psychogenic, the presence of one of these three symptoms was indicative of autoimmune encephalopathy. As autoimmune encephalitis exhibits diffuse involvement with the whole brain, these symptoms were entirely understandable. Except for the presence of organic disease, most patients were classified into somatoform disorders or functional movement disorders. Without first excluding autoimmune encephalopathy, physicians should not diagnose somatoform disorders.

DOI： 10.15082/jsnt.34.3_160

髙嶋博, 荒田仁, 東桂子, 松浦英治 . 子宮頸がんワクチンに関連した自己免疫脳症 . 神経治療学34 ( 6 ) S136 - S136 2017

Takashima Hiroshi, Kuwabara Satoshi, Kuriyama Masaru, Iizuka Takahiro . Discussion on Clinical Diversity of Various Encephalitis/Encephalopathy . Nihon Naika Gakkai Zasshi106 ( 8 ) 1598 - 1610 2017International journal

Yano C., Matsuura E., Nakamura T., Sonoda A., Shigehisa A., Ando M., Nozuma S., Higuchi Y., Sakiyama Y., Hashiguchi A., Michizono K., Takashima H. . Visual evoked potential in myelin oligodendrocyte glycoprotein antibody-associated disease . Multiple Sclerosis and Related Disorders98 106408 2025.6

Language：Japanese Publisher：Multiple Sclerosis and Related Disorders

The visual evoked potential (VEP) patterns of optic neuritis are known to often differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) but have been less reported in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This study aimed to characterize the VEP pattern in MOGAD and evaluate its utility in distinguishing MOGAD from MS and NMOSD. We retrospectively reviewed the clinical manifestations and VEP findings in patients with MS (n = 29), NMOSD (n = 14), and MOGAD (n = 10). In eyes with acute visual impairment, VEP responses were detectable in 100 % of eyes with MOGAD, a striking difference from MS (72.7 %) and NMOSD (57.1 %). In addition, VEP abnormalities in eyes without acute visual impairment were rare in MOGAD (23.1 %) compared to MS (55.3 %) and NMOSD (42.9 %). Our results indicated that subclinical VEP abnormalities or undetectable VEP responses were less common in patients with MOGAD compared to patients with MS and NMOSD. VEP testing demonstrates potential diagnostic utility in distinguishing among these conditions.

DOI： 10.1016/j.msard.2025.106408

Scopus

PubMed

Matsui N., Tanaka K., Kokubun N., Hatanaka Y., Ishida M., Osaki Y., Watanabe T., Watanabe O., Matsuura E., Takashima H., Sato Y., Kuwabara S., Izumi Y. . Prevalence, clinical profiles, and prognosis of Isaacs syndrome: A nationwide survey study in Japan . Journal of the Neurological Sciences472 123442 2025.5

Language：Japanese Publisher：Journal of the Neurological Sciences

Objectives: To elucidate current epidemiological, clinical, and immunological profiles, and the treatment of Isaacs syndrome in Japan. Methods: We conducted a nationwide survey using established methods. Questionnaires were sent to neurological facilities throughout Japan to identify Isaacs syndrome patients seen between April 2018 and March 2021. Results: The estimated total number of Isaacs syndrome patients was 114 (95 % confidence interval [CI]: 89.63–138.91), and the estimated prevalence was 0.091 per 100,000 population. Detailed clinical data were available for 44 patients. The median age at onset was 40 (range, 17–78 years), and 55 % were female. The median time from symptom onset to diagnosis was 24 months (range, 1–372 months). Electrodiagnostic studies showed evidence of nerve hyperexcitability in 90 % (myokymic discharges in 50 % and stimulus-induced repetitive discharges in 32 %). Of the 28 patients examined in the cell-based assay, 22 % tested positive (11 % for both leucine-rich glioma-inactivated 1 [LGI1] and contactin-associated protein-like 2 [CASPR2] antibodies and 11 % for LGI1 antibodies only). The median modified Rankin Scale (mRS) score was 2 at diagnosis and 1.5 at the last visit. A high mRS score (mRS ≥4) at baseline was an independent risk factor for poor outcomes (mRS ≥3) (Odds ratio, 20.7; 95 % CI, 2.90–209.18; p < 0.001). Conclusion: We elucidated the current epidemiological and clinical characteristics of Isaacs syndrome in Japan. Isaacs syndrome is a rare neuromuscular disorder. Electrophysiologic abnormalities were frequent, and serum antibodies were not detectable in the majority of patients. A high mRS score before treatment was a risk factor for poor outcomes.

DOI： 10.1016/j.jns.2025.123442

Scopus

PubMed

Peymani F, Ebihara T, Smirnov D, Kopajtich R, Ando M, Bertini E, Carrozzo R, Diodato D, Distelmaier F, Fang F, Ghezzi D, Hempel M, Iwanicka-Pronicka K, Klopstock T, Stenton SL, Lamperti C, Liu Z, Murtazina A, Okamoto Y, Okazaki Y, Piekutowska-Abramczuk D, Rötig A, Ryzhkova O, Schlein C, Shagina O, Takashima H, Tsygankova PG, Zech M, Meitinger T, Shimura M, Murayama K, Prokisch H . Pleiotropic effects of MORC2 derive from its epigenetic signature. . Brain : a journal of neurology 2025.4Pleiotropic effects of MORC2 derive from its epigenetic signature.

Masahiro Ando, Yujiro Higuchi, Jun-Hui Yuan, Akiko Yoshimura, Chikashi Yano, Takahiro Hobara, Fumikazu Kojima, Yu Hiramatsu, Satoshi Nozuma, Tomonori Nakamura, Yusuke Sakiyama, Akihiro Hashiguchi, Yuji Okamoto, Takeshi Matsushige, Jun Mitsui, Shoji Tsuji, Hiroshi Takashima . SOD1-related inherited peripheral neuropathies in a Japanese cohort: genetic variants and clinical insights. . Journal of neurology272 ( 3 ) 191 - 191 2025.3International journal

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

BACKGROUND: Inherited peripheral neuropathies (IPNs) encompass a wide range of disorders affecting the peripheral nervous system, often with complex genetic causes and frequent underdiagnosis. The variants in the superoxide dismutase 1 (SOD1) gene, primarily linked to amyotrophic lateral sclerosis (ALS), have also been associated with peripheral neuropathy. The recent approval of Tofersen, targeting SOD1-related ALS, highlights the importance of precise genetic diagnosis. This study explores the clinical and genetic profiles of SOD1-related IPNs (SOD1-IPN) in a nationwide Japanese IPN cohort. METHODS: Clinical and genetic data were assessed from 1483 Japanese patients with IPN, with a focus on those harboring SOD1 pathogenic variants. The clinical evaluations included age of onset, gender, muscle weakness patterns, sensory disturbances, reflex responses, and electrophysiological findings. RESULTS: Seventeen patients with SOD1 pathogenic variants were identified, reinforcing SOD1's role in IPN. The average onset age was 47, with a slight male predominance. Distal muscle weakness was noted in 9 of 13 patients, and asymmetric muscle weakness and atrophy in 10 of 14 cases. Mild sensory disturbances were observed in eight patients, with some showing hyperreflexia and abnormal reflexes. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy. CONCLUSION: This study reveals the clinical variability and likely underdiagnosis of SOD1-IPN, supporting the integration of SOD1 screening in IPN genetic testing, especially for patients with asymmetric, length-dependent axonal neuropathy evident in clinical and electrophysiological assessments.

DOI： 10.1007/s00415-025-12925-4

Scopus

PubMed

Nozuma S., Matsuzaki T., Tanaka M., Kodama D., Dozono M., Yoshida T., Takashima H., Kubota R. . T-Cell Receptor/CD3 Downregulation and Impaired Signaling in HTLV-1-Infected CD4+ T Cells of HAM Patients . International Journal of Molecular Sciences26 ( 4 ) 2025.2

Language：Japanese Publisher：International Journal of Molecular Sciences

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with adult T-cell leukemia (ATL), a hematological malignancy, and HTLV-1-associated myelopathy (HAM), a progressive neurological disorder. HTLV-1 predominantly infects CD4+ T cells in vivo. The T-cell receptor (TCR)/CD3 complex on CD4+ helper T cells plays a pivotal role in immune responses by recognizing antigens and facilitating coordination with other immune cells. Dysfunction of the TCR/CD3 complex may impair immune function. Although CD3 downregulation has been identified as a characteristic of ATL cells, it remains uncertain whether a similar downregulation occurs in HTLV-1-infected cells from HAM patients. We hypothesized that HTLV-1 infection leads to TCR and CD3 downregulation, contributing to immune dysfunction in HAM patients. To test this hypothesis, we analyzed TCR/CD3 expression, TCR signaling, and immune responses in HTLV-1-infected cells from HAM patients. Intracellular HTLV-1 Tax detection revealed that HTLV-1 preferentially targets CD4+ over CD8+ T cells. CD3 and TCR expression levels were significantly lower in CD4+ T cells from HAM patients compared to healthy controls. Furthermore, HTLV-1-infected cells exhibited markedly reduced CD3 and TCR expression compared to uninfected cells. Impairments in TCR signaling, assessed through Lck and ZAP70 phosphorylation upon CD3 stimulation, were observed in CD4+ T cells from HAM patients compared to those from healthy controls. Notably, this reduction in TCR signaling was more pronounced in HTLV-1-infected CD4+ T cells than in uninfected CD4+ T cells in HAM patients. Additionally, cytomegalovirus (CMV)-specific CD4+ T cells detected by an addition of CMV antigens demonstrated reduced interferon-γ production in HTLV-1-infected cells compared to their uninfected counterparts. These findings suggest that TCR/CD3 downregulation and impaired TCR signaling contribute to immune dysfunction in HTLV-1-infected CD4+ T cells. As CD4+ T cells play a central role in immune responses, this mechanism may partially explain the cellular immune dysfunction to other pathogens observed in HAM patients.

DOI： 10.3390/ijms26041706

Scopus

PubMed

Hiyoshi M., Eltalkhawy Y.M., Abdelnaser R.A., Ono A., Monde K., Maeda Y., Mahmoud R.M., Takahashi N., Hatayama Y., Ryo A., Nozuma S., Takashima H., Kubota R., Suzu S. . M-Sec promotes the accumulation of intracellular HTLV-1 Gag puncta and the incorporation of Env into viral particles . PLoS Pathogens21 ( 1 ) e1012919 2025.1

Language：Japanese Publisher：PLoS Pathogens

We have demonstrated that the cellular protein M-Sec promotes the transmission of human T-cell leukemia virus type 1 (HTLV-1) in vitro and in vivo. Here, we show how HTLV-1 utilizes M-Sec for its efficient transmission. HTLV-1-infected CD4+ T cells expressed M-Sec at a higher level than uninfected CD4+ T cells. The ex vivo culture of the infected cells upregulated the expression of M-Sec, the level of which was sustained for a long time. The viral structural protein Gag is distributed in a punctate pattern in cells. M-Sec promoted the accumulation of large intracellular Gag puncta. This accumulation was dependent on phosphatidylinositol 4,5-bisphosphate (PIP2), since it was lost upon the removal of PIP2 binding motifs in M-Sec or the depletion of cellular PIP2. The viral envelope protein Env co-localized with the large Gag puncta induced by M-Sec. Furthermore, viral particles produced by M-Sec-expressing cells contained a higher amount of Env. Given that M-Sec alters the cellular distribution of PIP2, these results suggest that M-Sec promotes the formation of infectious viral particles through PIP2. Since the expression of M-Sec is mediated by HTLV-1 Tax protein, M-Sec appears to function in a positive feedback loop that ensures efficient HTLV-1 transmission.

DOI： 10.1371/journal.ppat.1012919

Scopus

PubMed

Sakiyama Y., Yuan J.H., Yoshimura A., Takeuchi M., Maki Y., Mori T., Takei J., Ando M., Hiramatsu Y., Nozuma S., Higuchi Y., Yonezawa H., Kirishima M., Suzuki M., Kano T., Tarisawa M., Hashiguchi S., Kunii M., Sato S., Takahashi-Iwata I., Hashiguchi A., Matsuura E., Izumo S., Tanimoto A., Takashima H. . Brain biopsy and metagenomic sequencing enhance aetiological diagnosis of encephalitis . Brain Communications7 ( 3 ) fcaf165 2025

Language：Japanese Publisher：Brain Communications

Identifying the aetiology of CNS diseases, regardless of their infectious or non-infectious nature, is often intricate. Next-generation sequencing (NGS) has emerged as a powerful tool for sensitive and unbiased screening of tissue or body fluid specimens. This study aimed to investigate the underlying aetiology of patients with suspected infectious CNS diseases. Between April 2013 and October 2021, we collected brain tissue samples from 33 patients diagnosed with encephalitis or encephalitis-like CNS diseases, obtained via biopsy or autopsy, and underwent metagenomic NGS (mNGS) in conjunction with pathological evaluations. Moreover, we employed PCR-based assays and pathogen-specific immunostaining to corroborate the presence of pathogens within the tissue samples. Among the 33 patients, mNGS elucidated pathogen-specific genomic sequences in 7 cases (21.2%), including halobacteria (archaea), Balamuthia mandrillaris, Epstein-Barr virus, Toxoplasma gondii and herpes simplex virus. Additionally, brain tissue mNGS ruled out known pathogens, identifying 14 cases (42.4%) of non-infectious CNS diseases, which included neoplastic, autoimmune/inflammatory and amyloid angiopathy conditions. The adjustment of therapeutic strategies based on these findings led to improvements in clinical symptoms, imaging outcomes and patient prognosis. Brain biopsy serves as both a direct pathological research target and a valuable source of samples for unbiased high-throughput sequencing. Our study illustrates the reliability of mNGS on brain tissue, which significantly improves the diagnostic rate for suspected encephalitis or encephalitis-like diseases of unknown aetiology. These findings underscore the importance of mNGS in guiding more precise and effective therapeutic interventions for patients in clinical practice.

DOI： 10.1093/braincomms/fcaf165

Scopus

PubMed

矢野直志, 中村友紀, 髙嶋博 . Charcot-Marie-Tooth病の電気生理 . 臨床神経生理学52 ( 6 ) 686 - 690 2024.12Charcot-Marie-Tooth病の電気生理

Language：Japanese Publisher：一般社団法人日本臨床神経生理学会

Charcot-Marie-Tooth病 (CMT) は遺伝性ニューロパチーの一つである。CMTでは遺伝子型と表現型の多様性が知られており, 臨床所見のみから原因遺伝子を予測することが難しく, CMTとCIDPとの鑑別に悩むケースも少なくない。加えてCMTの病態に炎症機序が重畳することで免疫治療に部分的に反応する症例もあり, 治療反応性を重視しすぎると診断の誤りを招くことがある。今回, 日本における主要なCMTサブタイプとして, PMP22重複, MPZ, GJB1, MFN2, MME変異の電気生理学的特徴について概説し, CIDPとの鑑別点を検討した。多くのCMTの原因遺伝子が明らかになり, 従来の伝導ブロックや時間的分散の有無による先天性と後天性の鑑別は困難となってきている。繰り返し言及される点だが, 最終診断は病歴, 臨床所見, 電気生理学的所見, 遺伝子解析も含め総合的に行う必要がある。

DOI： 10.11422/jscn.52.686

Takahiro Hobara, Yujiro Higuchi, Mari Yoshida, Masahito Suehara, Masahiro Ando, Jun-Hui Yuan, Akiko Yoshimura, Fumikazu Kojima, Eiji Matsuura, Yuji Okamoto, Jun Mitsui, Shoji Tsuji, Hiroshi Takashima . Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications. . Acta neuropathologica communications12 ( 1 ) 136 - 136 2024.12International journal

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

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

DOI： 10.1186/s40478-024-01847-3

Scopus

PubMed

Chikada A., Orimo K., Mitsui J., Matsukawa T., Ishiura H., Toda T., Mizusawa H., Takahashi Y., Katsuno M., Hara K., Onodera O., Ishihara T., Tada M., Kuwabara S., Sugiyama A., Yamanaka Y., Takahashi R., Sawamoto N., Sakato Y., Ishimoto T., Hanajima R., Watanabe Y., Takigawa H., Adachi T., Abe K., Yamashita T., Takashima H., Higashi K., Kira J., Yabe I., Matsushima M., Ogata K., Ishikawa K., Nishida Y., Ishiguro T., Ozaki K., Nagata T., Tsuji S. . The Japan MSA registry: A multicenter cohort study of multiple system atrophy . Neurology and Clinical Neuroscience12 ( 5 ) 271 - 277 2024.9

Language：Japanese Publisher：Neurology and Clinical Neuroscience

Background: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure and various motor symptoms. While MSA-C (cerebellar type) predominates in East Asia, MSA-P (parkinsonian type) predominates in Europe and North America. This nationwide patient registry aimed to (1) conduct a prospective natural history study of MSA in Japan, (2) facilitate patient recruitment for clinical trials, and (3) deposit bioresources and clinical information in a biobank. Methods: Thirteen institutions participated in this study. Clinical information was obtained by neurologists from the patients visiting the hospital every 12 months to assess the UMSARS Part 2 scores and by telephone interviews by nurses every 6 months to assess UMSARS Part 1 scores and to determine whether clinical events had occurred. Results: Demographic data from 329 MSA patients (216 MSA-C and 113 MSA-P) were analyzed. The mean age at symptom onset was 58.2 years (standard deviation, 8.9); the mean duration of symptoms at enrollment was 3.5 years (standard deviation, 2.2). The mean 12-month changes in the UMSARS Part 1 and Part 2 scores were 7.9 (standard deviation, 5.6) and 6.4 (standard deviation, 5.9), respectively. The patient registry proved useful in recruiting participants for clinical trials, including those with gene variants. Clinical information and biospecimens were deposited in a biobank. Discussion: The study highlighted the importance of telephone interviews in minimizing drop-out rates in natural history studies and demonstrated similar MSA progression rates across populations. The deposited bioresources are available to researchers upon request, aiming to contribute to future MSA researches.

DOI： 10.1111/ncn3.12809

Scopus

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)

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。

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

Scopus

PubMed

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(タイトル和訳中) . Internal Medicine63 ( 15 ) 2183 - 2186 2024.8Writer's Cramps as an Initial Symptom of Spinocerebellar Ataxia Type 14(タイトル和訳中)

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

Scopus

PubMed

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

Scopus

PubMed

　 PREV - NEXT 　

<TAKASHIMA Hiroshi>

Papers - TAKASHIMA Hiroshi