- Multiple System Atrophy: Advances in Diagnosis and Therapy
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Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito
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J Mov Disord. 2023;16(1):13-21. Published online December 20, 2022
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DOI: https://doi.org/10.14802/jmd.22082
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- 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.
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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
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- Clinical and Imaging Features of Multiple System Atrophy: Challenges for an Early and Clinically Definitive Diagnosis
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Hirohisa Watanabe, Yuichi Riku, Kazuhiro Hara, Kazuya Kawabata, Tomohiko Nakamura, Mizuki Ito, Masaaki Hirayama, Mari Yoshida, Masahisa Katsuno, Gen Sobue
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J Mov Disord. 2018;11(3):107-120. Published online August 9, 2018
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DOI: https://doi.org/10.14802/jmd.18020
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- 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.
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