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Mizuki Ito 2 Articles
Multiple System Atrophy: Advances in Diagnosis and Therapy
Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito
J Mov Disord. 2023;16(1):13-21.   Published online December 20, 2022
  • 4,627 View
  • 444 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDF
This review summarizes improvements in understanding the pathophysiology and early clinical symptoms of multiple system atrophy (MSA) and advancements in diagnostic methods and disease-modifying therapies for the condition. In 2022, the Movement Disorder Society proposed new diagnostic criteria to develop disease-modifying therapies and promote clinical trials of MSA since the second consensus was proposed in 2008. Regarding pathogenesis, cutting-edge findings have accumulated on the interactions of α-synuclein, neuroinflammation, and oligodendroglia with neurons. In neuroimaging, introducing artificial intelligence, machine learning, and deep learning has notably improved diagnostic accuracy and individual analyses. Advancements in treatment have also been achieved, including immunotherapy therapy against α-synuclein and serotonin-targeted and mesenchymal stem cell therapies, which are thought to affect several aspects of the disease, including neuroinflammation. The accelerated progress in clarifying the pathogenesis of MSA over the past few years and the development of diagnostic techniques for detecting early-stage MSA are expected to facilitate the development of disease-modifying therapies for one of the most intractable neurodegenerative diseases.


Citations to this article as recorded by  
  • A Blinded Evaluation of Brain Morphometry for Differential Diagnosis of Atypical Parkinsonism
    Kazuya Kawabata, Florian Krismer, Beatrice Heim, Anna Hussl, Christoph Mueller, Christoph Scherfler, Elke R. Gizewski, Klaus Seppi, Werner Poewe
    Movement Disorders Clinical Practice.2024; 11(4): 381.     CrossRef
  • The potential of phosphorylated α‐synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy
    Toufik Abdul‐Rahman, Ranferi Eduardo Herrera‐Calderón, Arjun Ahluwalia, Andrew Awuah Wireko, Tomas Ferreira, Joecelyn Kirani Tan, Maximillian Wolfson, Shankhaneel Ghosh, Viktoriia Horbas, Vandana Garg, Asma Perveen, Marios Papadakis, Ghulam Md Ashraf, Ath
    CNS Neuroscience & Therapeutics.2024;[Epub]     CrossRef
  • Delivering the diagnosis of multiple system atrophy: a multicenter survey on Japanese neurologists’ perspectives
    Miki Yoshitake, Atsuhiko Sugiyama, Takayoshi Shimohata, Nobuyuki Araki, Masahide Suzuki, Kazumoto Shibuya, Kengo Nagashima, Nobutaka Hattori, Satoshi Kuwabara
    BMC Neurology.2024;[Epub]     CrossRef
Clinical and Imaging Features of Multiple System Atrophy: Challenges for an Early and Clinically Definitive Diagnosis
Hirohisa Watanabe, Yuichi Riku, Kazuhiro Hara, Kazuya Kawabata, Tomohiko Nakamura, Mizuki Ito, Masaaki Hirayama, Mari Yoshida, Masahisa Katsuno, Gen Sobue
J Mov Disord. 2018;11(3):107-120.   Published online August 9, 2018
  • 19,173 View
  • 1,217 Download
  • 25 Web of Science
  • 27 Crossref
AbstractAbstract PDF
Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder. Patients with MSA show various phenotypes during the course of their illness, including parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal signs. Patients with MSA sometimes present with isolated autonomic failure or motor symptoms/ signs. The median duration from onset to the concomitant appearance of motor and autonomic symptoms is approximately 2 years but can range up to 14 years. As the presence of both motor and autonomic symptoms is essential for the current diagnostic criteria, early diagnosis is difficult when patients present with isolated autonomic failure or motor symptoms/signs. In contrast, patients with MSA may show severe autonomic failure and die before the presentation of motor symptoms/signs, which are currently required for the diagnosis of MSA. Recent studies have also revealed that patients with MSA may show nonsupporting features of MSA such as dementia, hallucinations, and vertical gaze palsy. To establish early diagnostic criteria and clinically definitive categorization for the successful development of disease-modifying therapy or symptomatic interventions for MSA, research should focus on the isolated phase and atypical symptoms to develop specific clinical, imaging, and fluid biomarkers that satisfy the requirements for objectivity, for semi- or quantitative measurements, and for uncomplicated, worldwide availability. Several novel techniques, such as automated compartmentalization of the brain into multiple parcels for the quantification of gray and white matter volumes on an individual basis and the visualization of α-synuclein and other candidate serum and cerebrospinal fluid biomarkers, may be promising for the early and clinically definitive diagnosis of MSA.


Citations to this article as recorded by  
  • Cranial Nerve Thinning Distinguishes RFC1‐Related Disorder from Other Late‐Onset Ataxias
    Camila C. Lobo, Guilherme S.O. Wertheimer, Gabriel S. Schmitt, Paula C.A.A.P. Matos, Thiago J.R. Rezende, Joyce M. Silva, Fabrício C. Borba, Fabrício D. Lima, Alberto R.M. Martinez, Orlando G.P. Barsottini, José Luiz Pedroso, Wilson Marques, Marcondes C.
    Movement Disorders Clinical Practice.2024; 11(1): 45.     CrossRef
  • The potential of phosphorylated α‐synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy
    Toufik Abdul‐Rahman, Ranferi Eduardo Herrera‐Calderón, Arjun Ahluwalia, Andrew Awuah Wireko, Tomas Ferreira, Joecelyn Kirani Tan, Maximillian Wolfson, Shankhaneel Ghosh, Viktoriia Horbas, Vandana Garg, Asma Perveen, Marios Papadakis, Ghulam Md Ashraf, Ath
    CNS Neuroscience & Therapeutics.2024;[Epub]     CrossRef
  • Data-Driven Subtypes of Multiple System Atrophy and Their Implications for Prognosis
    Cheng-Cheng Fan, Chao Han, Xue-Mei Wang, Jagadish K. Chhetri, Wei Mao, Er-He Xu, Shu-Ying Liu, Piu Chan
    Journal of Parkinson's Disease.2024; : 1.     CrossRef
  • The effect of continuous positive airway pressure (CPAP) on the quality of life in patients with multiple system atrophy
    Hee Jin Chang, Han-Joon Kim, Kyung Ah Woo, Jung Hwan Shin, Ki-Young Jung
    Sleep and Breathing.2023; 27(4): 1481.     CrossRef
  • Psychosis treatment in a patient with Parkinsonian type multiple system atrophy using modified electroconvulsive therapy: a case report
    Takumi Yawata, Shunsuke Takagi, Takehiro Tamura, Genichi Sugihara, Hidehiko Takahashi
    Psychogeriatrics.2023; 23(2): 364.     CrossRef
  • Comparison of the second consensus statement with the movement disorder society criteria for multiple system atrophy: A single-center analysis
    Yunchuang Sun, Wei Sun, Luhua Wei, Fan Li, Yanyan Jiang, Fei Zhai, Mingyue Luan, Jing Chen, Zhaoxia Wang
    Parkinsonism & Related Disorders.2023; 106: 105242.     CrossRef
  • Multiple System Atrophy: Advances in Diagnosis and Therapy
    Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito
    Journal of Movement Disorders.2023; 16(1): 13.     CrossRef
  • Multiple system atrophy-cerebellar: A case report and literature review
    Thi Thuong Doan, Thuy Dung Pham, Duy Duan Nguyen, Dac Hong An Ngo, Trong Binh Le, Thanh Thao Nguyen
    Radiology Case Reports.2023; 18(3): 1121.     CrossRef
  • Hjerne med kors
    Linh Tran, Tuba Ahmad, Anniken Haslund, Phuoc Ngoc Thi Nguyen
    Tidsskrift for Den norske legeforening.2023;[Epub]     CrossRef
  • α-Synuclein Strains and Their Relevance to Parkinson’s Disease, Multiple System Atrophy, and Dementia with Lewy Bodies
    Noah J. Graves, Yann Gambin, Emma Sierecki
    International Journal of Molecular Sciences.2023; 24(15): 12134.     CrossRef
  • A Rare Case of Cerebellar Ataxia
    Aanchal Arora, Nidhi Hooda, JasneetSingh Channa, Motilal Negi
    Neurology India.2023; 71(5): 1031.     CrossRef
  • Neurodegenerative disorders affecting the autonomic nervous system: Pure autonomic failure and multiple system atrophy
    Yoshitaka Yamanaka, Nobuyuki Araki, Satoshi Kuwabara
    Neurology and Clinical Neuroscience.2022; 10(3): 115.     CrossRef
  • Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Positron Emission Tomography Study with [11C]PBR28 and Machine Learning Analysis
    Aurelija Jucaite, Zsolt Cselényi, William C. Kreisl, Eugenii A. Rabiner, Andrea Varrone, Richard E. Carson, Juha O. Rinne, Alicia Savage, Magnus Schou, Peter Johnström, Per Svenningsson, Olivier Rascol, Wassilios G. Meissner, Paolo Barone, Klaus Seppi, Ho
    Movement Disorders.2022; 37(1): 119.     CrossRef
  • Data-driven subtype classification of patients with early-stage multiple system atrophy
    Hui-Jun Yang, Han-Joon Kim, Yu Jin Jung, Dallah Yoo, Ji-Hyun Choi, Jin Hee Im, Beomseok Jeon
    Parkinsonism & Related Disorders.2022; 95: 92.     CrossRef
  • Clinicopathological correlates of pyramidal signs in multiple system atrophy
    Chi‐Ying R. Lin, Anisha Viswanathan, Tiffany X. Chen, Hiroshi Mitsumoto, Jean P. Vonsattel, Phyllis L. Faust, Sheng‐Han Kuo
    Annals of Clinical and Translational Neurology.2022; 9(7): 988.     CrossRef
  • The “Black Straight-Line Sign” in the Putamen in Diffusion-Weighted Imaging: A Potential Diagnostic MRI Marker for Multiple System Atrophy
    Yiming Zheng, Xiwen Wang, Huajian Zhao, Yanyan Jiang, Ying Zhu, Jing Chen, Wei Sun, Zhaoxia Wang, Yunchuang Sun
    Frontiers in Neurology.2022;[Epub]     CrossRef
  • Clinical Aspects of the Differential Diagnosis of Parkinson’s Disease and Parkinsonism
    Hae-Won Shin, Sang-Wook Hong, Young Chul Youn
    Journal of Clinical Neurology.2022; 18(3): 259.     CrossRef
  • Clinical Features and Neuroimaging Findings of Neuropil Antibody–Positive Idiopathic Sporadic Ataxia of Unknown Etiology
    Akira Takekoshi, Akio Kimura, Nobuaki Yoshikura, Isamu Yamakawa, Makoto Urushitani, Katsuya Nakamura, Kunihiro Yoshida, Takayoshi Shimohata
    The Cerebellum.2022; 22(5): 915.     CrossRef
  • Determinants of cognitive impairment in multiple system atrophy: Clinical and genetic study
    Amina Nasri, Alya Gharbi, Ikram Sghaier, Saloua Mrabet, Amira Souissi, Amina Gargouri, Mouna Ben Djebara, Imen Kacem, Riadh Gouider, Tuhin Virmani
    PLOS ONE.2022; 17(12): e0277798.     CrossRef
  • Management of balance problems in an elderly with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sick sinus syndrome
    Amber Eker, Pembe Hare Yıgıtoglu, Hamza Duygu, Ersin Tan
    Journal of Gerontology and Geriatrics.2021; 69(3): 208.     CrossRef
  • Immunotherapies in Huntington's disease and α-Synucleinopathies
    Oluwaseun Fatoba, Yosuke Ohtake, Takahide Itokazu, Toshihide Yamashita
    Frontiers in Immunology.2020;[Epub]     CrossRef
  • The Dysfunctional Autonomic Function and “Dysfunctional” Fatigue in Drug Naïve Parkinson’s Disease
    Jong Hyeon Ahn, Minkyeong Kim, Jun Kyu Mun, Yoonsu Cho, Ji Sun Kim, Jinyoung Youn, Joong-Seok Kim, Jin Whan Cho
    Journal of Parkinson's Disease.2020; 10(2): 605.     CrossRef
  • Early autonomic and cognitive dysfunction in PD, DLB and MSA: blurring the boundaries between α-synucleinopathies
    Giovanni Palermo, Eleonora Del Prete, Ubaldo Bonuccelli, Roberto Ceravolo
    Journal of Neurology.2020; 267(12): 3444.     CrossRef
  • Changes of Amide Proton Transfer Imaging in Multiple System Atrophy Parkinsonism Type
    Shuhua Li, Piu Chan, Chunmei Li, Haibo Chen, Min Chen, Wen Su, Kai Li, Na Lu, Lu Yu, Defa Chu, Pu-Yeh Wu
    Frontiers in Aging Neuroscience.2020;[Epub]     CrossRef
  • Frontline of Non-genetic Cerebellar Ataxia
    Nobuaki Yoshikura, Akio Kimura, Takayoshi Shimohata
    Nihon Naika Gakkai Zasshi.2020; 109(6): 1138.     CrossRef
  • Purva Rupeeyam of bhela indriya sthana-an explorative study
    Kshama Gupta, Prasad Mamidi
    International Journal of Complementary & Alternative Medicine.2020; 13(6): 228.     CrossRef
  • A case of multiple system atrophy
    Jing Guo, Fuying Liu, Tingting Liu, Xin Zhang, Yong Luo
    Journal of International Medical Research.2019; 47(11): 5839.     CrossRef

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