Takahashi, Yuji
https://orcid.org/0000-0001-5335-7757
Mayo Clinic
National Center of Neurology and Psychiatry
Citations 2
Revisiting ‘hot cross bun’ sign: a multicentre MRI study of 97 patients with autopsy-confirmed multiple system atrophy
Sugiyama, Atsuhiko , Mukai, Hiroki , Takao, Masaki , Takeda, Takahiro , Hirano, Shigeki , Yoshida, Mari , Yasui, Keizo, Ando, Takashi , Tamura, Takuya, Middlebrooks, Erik H. , Takahashi, Yuji , Mizutani, Masashi , Mihara, Ban , Komori, Takashi , Hirano, Shigeki , Yoshida, Mari , Ando, Takashi , Sekiya, Hiroaki , Sano, Terunori , Kuwabara, Satoshi , Middlebrooks, Erik H , Riku, Yuichi , Koga, Shunsuke , Yokota, Hajime , Hayashi, Kentarō , Takeda, Takahiro, Iwasaki, Yasushi , Yasui, Keizo, Ito, Yasuhiro , Sekiya, Hiroaki , Dickson, Dennis W. , Sato, Noriko , Komori, Takashi, Kuwabara, Satoshi
Journal of Neurology, Neurosurgery & Psychiatry | October 13, 2025 | Volume: No volume available | Issue: No issue available | Pages: jnnp-2025-336869
Background The purpose of this study was to clarify the usefulness of the ‘hot cross bun’ sign (HCBS) as a diagnostic imaging marker in a large cohort of patients with multiple system atrophy (MSA) and spinocerebellar ataxia (SCA). Methods This multicentre study included 97 patients with neuropathologically confirmed MSA, and 105 patients with genetically confirmed SCA. Neuroimaging features, including HCBS and middle cerebellar peduncle (MCP) hyperintensities, were assessed. HCBS was graded from 0 to 2: 0, none; 1, only a vertical hyperintense line; and 2, a cruciform hyperintense line. The neuropathological correlates of HCBS were evaluated in 15 patients with MSA with ≤3 months between MRI and autopsy. Results In patients with a disease duration <3 years, grade 1 or 2 HCBS was detected in 100% patients with MSA with predominant cerebellar ataxia (MSA-C) and 39.0% with SCA; whereas grade 2 HCBS was observed in 50% with MSA-C and 2.4% with SCA. Moreover, the coexistence of grade 2 HCBS and MCP hyperintensities exhibited a specificity of 100%. A neuropathological assessment revealed myelin loss, alpha-synuclein aggregates and astrocytic reaction in the MCP, transverse fibres, central zone between longitudinal fasciculi and raphe nucleus, with relative preservation in the longitudinal fasciculi and medial lemniscus in patients with MSA and grade 2 HCBS. Conclusions Grade 1 or 2 HCBS is a highly sensitive finding in patients with MSA-C, and the observation of grade 2 HCBS within 3 years of motor symptom onset has excellent specificity for discriminating MSA-C from SCA, especially when accompanied by MCP hyperintensities.
Genome-wide association analysis identifies PLA2G4C as a susceptibility locus for Multiple System Atrophy
Tsuji, Shoji , Nakahara, Yasuo , Mitsui, Jun , Date, Hidetoshi, Porto, Kristine Joyce L. , Hyashi, Y., Kusakabe, Yoshio , Matsukawa, Takashi , Ishiura, Hiroyuki , Yasuda, Tsutomu , Goto, Jun , Ichikawa, Yaeko, Momose, Yoshio, Takahashi, Yuji , Ohta, Rikifumi , Yoshimura, Jun , Gustavsson, Emil K. , Christy, Darren, Maczis, Melisa, Gu, Weihong, Scholz, Sonja W. , Houlden, Henry , Sasaki, Hidenao , Kikuchi, Akio , Hara, Kenju , Kakita, Akiyoshi , Yamada, Mitsunori , Nishizawa, Masatoyo , Ito, Mizuki , Sobue, Gen , Ishikawa, Kinya , Mizusawa, Hidehiro, Kanai, Kazuaki , Arai, Kimihito , Koyano, Shigeru , Kuroiwa, Yoshiyuki , Hasegawa, Kazuko, Yuasa, Tatsuhiko, Yasui, Kenichi, Ito, Hijiri, Izumi, Yuishin , Kaji, Ryuji , Kato, Takeo , Kusunoki, Susumu , Osaki, Yasushi , Horiuchi, Masahiro , Yamamoto, Ken , Shimada, Mihoko , Miyagawa, Taku , Nishida, Nao , Tokunaga, Katsushi , Filla, Alessandro , Klockgether, Thomas , Wuellner, Ullrich, Kukull, Walter A. , Masliah, Eliezer , Low, Phillip A. , Sandroni, Paola , Ozelius, Laurie J. , Trojanowski, John Q. , Scholz, Sonja W , Houlden, Henry , Yamashita, Atsushi , Yasuda, Tsutomu, Iwata, Atsushi , Toda, Tatsushi , Morishita, Shinichi , Kim, Han‐Joon , Park, Sung Sup , Zhang, Jin , Chelban, Viorica , Mok, Kin Ying , Yabe, Ichiro , Matsushima, Masaaki , Takashima, Hiroshi , Aoki, Masashi , Takahashi, Hitoshi , Onodera, Osamu , Watanabe, Hirohisa , Kuwabara, Satoshi , Nakashima, Kenji , Horiuchi, Masahiro, Kawai, Yosuke , Dürr, Alexandra , Brice, Alexis , Tanner, Caroline M. , Lee, Virginia M.‐Y. , Foroud, Tatiana , Farrer, Matthew J.
No container title available | February 6, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract 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 (P = 6.5 × 10− 7) that was replicated in additional Japanese samples (P = 2.9 × 10− 6, odds ratio (OR) = 1.58; 95% confidence interval (CI), 1.30–1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data (P = 5.0 × 10− 15, OR = 1.49; 95% CI 1.35–1.65). The association of rs2303744 with MSA remained significant in combined European/North American samples (P = 0.017, OR = 1.12; 95% CI 1.02–1.23) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in PLA2G4C 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, and may perturb membrane phospholipids and promote oligodendroglial pathology.