Faculty Profiles - TAKASHIMA Hiroshi

Takaki Taniguchi , Masahiro Ando , Yuji Okamoto , Akiko Yoshimura , Yujiro Higuchi , Akihiro Hashiguchi , Kensuke Shiga , Arisa Hayashida , Taku Hatano , Hiroyuki Ishiura , Jun Mitsui , Nobutaka Hattori , Toshiki Mizuno , Masanori Nakagawa , Shoji Tsuji , Hiroshi Takashima . Genetic spectrum of Charcot–Marie–Tooth disease associated with myelin protein zero gene variants in Japan . Clinical Genetics99 ( 3 ) 359 - 375 2021.3Reviewed International journal

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

We aimed to reveal the genetic features associated with MPZ variants in Japan. From April 2007 to August 2017, 64 patients with 23 reported MPZ variants and 21 patients with 17 novel MPZ variants were investigated retrospectively. Variation in MPZ variants and the pathogenicity of novel variants was examined according to the American College of Medical Genetics standards and guidelines. Age of onset, cranial nerve involvement, serum creatine kinase (CK), and cerebrospinal fluid (CSF) protein were also analyzed. We identified 64 CMT patients with reported MPZ variants. The common variants observed in Japan were different from those observed in other countries. We identified 11 novel pathogenic variants from 13 patients. Six novel MPZ variants in eight patients were classified as likely benign or uncertain significance. Cranial nerve involvement was confirmed in 20 patients. Of 30 patients in whom serum CK levels were evaluated, eight had elevated levels. Most of the patients had age of onset >20 years. In another subset of 30 patients, 18 had elevated CSF protein levels; four of these patients had spinal diseases and two had enlarged nerve root or cauda equina. Our results suggest genetic diversity across patients with MPZ variants.

DOI： 10.1111/cge.13881

Inada R, Hirano M, Oka N, Samukawa M, Saigoh K, Suzuki H, Udaka F, . Phenotypic and molecular diversities of spinocerebellar ataxia type 2 in Japan . 268 ( 8 ) 2933 - 2942 2021.2Invited Reviewed International journal

M.D. Douzono Mika, M.D. Ph.D. Nobuhara Yasuyuki, M.D. Ph.D. Maruta Kyouko, M.D. Ph.D. Okamoto Yuji, M.D. Ph.D. Sonoda Yoshito, M.D. Ph.D. Takashima Hiroshi . Inherited Creutzfeldt–Jakob disease with four-octapeptide repeat insertional mutation in the prion gene . Rinsho Shinkeigaku61 ( 5 ) 314 - 318 2021

Language：Japanese Publisher：Societas Neurologica Japonica

We report a case of a 60-year-old man who presented with symptoms of memory loss, gait disorder, and sluggish movement. We considered both Parkinson's disease and multiple system atrophy as possible diagnoses and consequently hospitalized the patient owing to the worsening symptoms and the development of consciousness disorder. During the course of the disease, dementia, loss of consciousness, and movement disorders worsened rapidly within one year after admission, and the patient eventually developed mutism. The significant clinical characteristics of our case included no myoclonus and involuntary tremors in the extremities. There was no periodic synchronous discharge on electroencephalography and cranial MRI with diffusion-weighted images showed no high-intensity findings in cortex. Prion protein genetic analysis identified four repeated insertional mutations in the octapeptide repeat (OPR) region, and the patient was diagnosed with inherited Creutzfeldt–Jakob disease. Cases of OPR insertional mutations are a few in Japan and occur in about 10% of population in Europe. Creutzfeldt–Jakob disease with OPR insertional mutation shows various clinical manifestations and atypical findings on electroencephalography and cranial MRI. Diagnosing for Creutzfeldt–Jakob disease with OPR insertional mutation is important in Prion protein genetic analysis.

DOI： 10.5692/clinicalneurol.cn-001558

Satomi D. . Limits to the exaggeration and diversification of a male sexual trait in the false blister beetle Oedemera sexualis . Entomological Science24 ( 3 ) 219 - 227 2021

Language：Japanese Publisher：Entomological Science

Differentiation in sexual traits among populations is one of the major predictions of theories of sexual selection and sexual conflict. A balance between maximizing reproductive benefits and minimizing survival costs could explain variation in sexual traits within and between populations. The false blister beetle Oedemera sexualis (Coleoptera: Oedemeridae) has exaggerated sexual traits, that is, sexually dimorphic hindlegs. In this study, we characterized scaling relationships in populations of O. sexualis to evaluate the determinants of sexual trait variation in the species. We quantified sexual dimorphism in body size and hindleg sizes in three representative populations based on distance measurements and an elliptical Fourier analysis. We found significant variation in the degree of sexual dimorphism for body and hindleg sizes among populations. In particular, differentiation in the male hind femur shape, especially the femur width, was conspicuous. Scaling relationships between male hind femur width and body size were best described by logistic models, showing that increases in male hind femur width were constrained for large individuals in all three populations. The degree of constrained growth of the hind femur width differed among populations in accordance with the population means, while the basal growth rates did not. Populations with smaller mean values for sexual traits showed more limited sexual trait exaggeration, contrary to the predictions based on resource competition among body parts. The latitudinal cline in femur widths suggests that environmental constraints on exaggeration might be responsible for sexual trait diversification in O. sexualis.

DOI： 10.1111/ens.12469

髙嶋博 . 脊髄性筋萎縮症の遺伝子治療の実際とその未来 . 神経治療学38 ( 6 ) S178 - S178 2021

Aoki Sho, Nagashima Kazuaki, Shibata Makoto, Kasahara Hiroo, Fujita Yukio, Hashiguchi Akihiro, Takashima Hiroshi, Ikeda Yoshio . Sibling Cases of Charcot-Marie-Tooth Disease Type 4H with a Homozygous FGD4 Mutation and Cauda Equina Thickening . Internal Medicine60 ( 24 ) 3975 - 3981 2021

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H with a homozygous mutation in the FGD4 gene. Both patients exhibited cauda equina thickening on magnetic resonance imaging, which had not been reported among the previous CMT4H cases. This is the first report of CMT4H with a homozygous FGD4 c.1730G>A (p.Arg577Gln) mutation showing mild progression and cauda equina thickening.

DOI： 10.2169/internalmedicine.7247-21

Yamagishi Y. . Serum IgG anti-GD1a antibody and mEGOS predict outcome in Guillain-Barré syndrome . Journal of Neurology, Neurosurgery and Psychiatry91 ( 12 ) 1339 - 1342 2020.12Reviewed International journal

Sakiyama Yusuke, Matsuura Eiji, Shigehisa Ayano, Hamada Yuki, Dozono Mika, Nozuma Satoshi, Nakamura Tomonori, Higashi Keiko, Hashiguchi Akihiro, Takahashi Yukitoshi, Takashima Hiroshi . Cryptococcus Meningitis Can Co-occur with Anti-NMDA Receptor Encephalitis . 59 ( 18 ) 2301 - 2306 2020.9

Kodama D. . Inhibition of abl1 tyrosine kinase reduces htlv-1 proviral loads in peripheral blood mononuclear cells from patients with htlv-1-associated myelopathy/tropical spastic paraparesis . PLoS Neglected Tropical Diseases14 ( 7 ) 1 - 21 2020.7Reviewed International journal

Ishihara S, Okamoto Y, Tanabe H, Yoshimura A, Higuchi Y, Yuan JH, Hashiguchi . Clinical features of inherited neuropathy with BSCL2 mutations in Japan . Journal of the peripheral nervous system : JPNS25 ( 2 ) 125 - 131 2020.6Reviewed International journal

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have been reported with different clinical phenotypes including Silver syndrome (SS)/spastic paraplegia 17 (SPG17), distal hereditary motor neuropathy type V (dHMN-V), and Charcot-Marie-Tooth (CMT) disease type 2. We screened 407 Japanese patients who were clinically suspected of having CMT by exome sequencing and searched mutations in BSCL2. As a result, we identified five patients with heterozygous mutations in BSCL2. We confirmed three cases of known mutations (p.N88S and p.S90L) and two cases of novel mutations (p.N88T and p.S141A). The clinical features of the cases with known mutations in Japan were similar to those previously reported in other countries. In particular, there were many cases with sensory disturbance. The case with p.N88T mutation showed severe phenotype such as early onset age and prominent vocal cord paresis. The case with p.S141A mutation showed characteristics of demyelinating neuropathy such as CMT disease type 1 by electrophysiological examination. In this article, we report the clinical features and spread of cases with BSCL2 mutation in a Japanese cohort.

DOI： 10.1111/jns.12369

Yamagishi Y, Samukawa M, Kuwahara M, Takada K, Saigoh K, Mitsui Y, Oka N, Hashiguchi A, Takashima H, Kusunoki S. . Charcot-Marie-Tooth Disease With a Mutation in FBLN5 Accompanying With the Small Vasculitis and Widespread Onion-Bulb Formations . J Neurol Sci. 410 2020.3Reviewed

Nishizawa M, Onodera O, Hirakawa A, Shimizu Y, Yamada M; Rovatirelin Study . Effect of rovatirelin in patients with cerebellar ataxia: two randomised . J Neurol Neurosurg Psychiatry.91 ( 3 ) 254 - 262 2020.3

Sawada Jun, Yoshimura Akiko, Takashima Hiroshi, Hasebe Naoyuki, Katayama Takayuki, Tokashiki Takashi, Kikuchi Shiori, Kano Kohei, Takahashi Kae, Saito Tsukasa, Adachi Yoshiki, Okamoto Yuji . The First Case of Spinocerebellar Ataxia Type 8 in Monozygotic Twins . Internal Medicine59 ( 2 ) 277 - 283 2020.1Reviewed

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine

Spinocerebellar ataxia type 8 (SCA8) is a rare hereditary cerebellar ataxia showing mainly pure cerebellar ataxia. We herein report cases of SCA8 in Japanese monozygotic twins that presented with nystagmus, dysarthria, and limb and truncal ataxia. Their ATXN8OS CTA/CTG repeats were 25/97. They showed similar manifestations, clinical courses, and cerebellar atrophy on magnetic resonance imaging. Some of their pedigrees had nystagmus but not ataxia. These are the first monozygotic twins with SCA8 to be reported anywhere in the world. Although not all subjects with the ATXN8OS CTG expansion develop cerebellar ataxia, these cases suggest the pathogenesis of ATXN8OS repeat expansions in hereditary cerebellar ataxia.

DOI： 10.2169/internalmedicine.2905-19

Takashima Hiroshi . Symptoms of autoimmune encephalopathy ―Differentiation from hysteria― . Neurological Therapeutics37 ( 4 ) 636 - 639 2020Reviewed

Authorship：Lead author,　Last author,　Corresponding 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 misdiagnosed as exhibiting functional psychogenic movement, conversion, or somatoform disorders. Most patients with autoimmune encephalopathy showed motor disturbance mostly with unsustained and/or give–way weakness. About 70% of patients showed sensory abnormalities that was not explainable anatomically. One–fourth of patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. 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.37.4_636

Yoshimura A, Yuan JH, Hashiguchi A, Ando M, Higuchi Y, Nakamura T, Okamoto Y, Nakagawa M, Takashima H . Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan. . Journal of neurology, neurosurgery, and psychiatry90 ( 2 ) 195 - 202 2019.2Reviewed International journal

Takashima Hiroshi . Clinical symptoms of autoimmune encephalopathy　―Differentiation from hysteria― . Neurological Therapeutics36 ( 4 ) 341 - 344 2019Reviewed

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. We often recognize that patients with autoimmune encephalopathy are often misdiagnosed as functional psychogenic movement or somatoform disorders. We have reported 63 patients with autoimmune encephalopathy. Two–thirds of patients showed motor disturbance mostly with unsustained or give–way weakness. About 70% of patients showed sensory abnormalities that was not explainable anatomically. 27% of patients exhibited involuntary movements such as tremor entrainment, dystonia, or coarse involuntary movement. 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.36.4_341