Multiple system atrophy: advances in pathophysiology, diagnosis, and treatment.

Multiple system atrophy is an adult-onset, sporadic, and progressive neurodegenerative disease. People with this disorder report a wide range of motor and non-motor symptoms. Overlap in the clinical presentation of multiple system atrophy with other movement disorders (eg, Parkinson's disease and progressive supranuclear palsy) is a concern for accurate and timely diagnosis. Over the past 5 years, progress has been made in understanding key pathophysiological events in multiple system atrophy, including the seeding of α-synuclein inclusions and the detection of disease-specific α-synuclein strains. Diagnostic criteria were revised in 2022 with the intention to improve the accuracy of a diagnosis of multiple system atrophy, particularly for early disease stages. Early signals of efficacy in clinical trials have indicated the potential for disease-modifying therapies for multiple system atrophy, although no trial has yet provided unequivocal evidence of neuroprotection in this rare disease. The advances in pathophysiology could play a part in biomarker discovery for early diagnosis as well as in the development of disease-modifying therapies.
Competing Interests: Declaration of interests FK received personal fees from Institut de Recherches Internationales Servier, Takeda Pharmaceuticals, Sanofi, Teva, Bial, and the Austrian Society of Neurology in the past 36 months and he has ongoing grant support from the Austrian Science Fund, the National Institutes of Health, and the Michael J Fox Foundation, outside of the submitted work. AF reports grant support from the Austrian Science Fund, Multiple System Atrophy Coalition, Austrian Exchange Program, Medical University of Innsbruck, Tuba Stiftung; royalties from Springer and Thieme; and personal fees from Broadview Ventures, Theravance, Bial, Abbvie, GE Health Care, Austrian Neurology Society, Austrian Autonomic Society, International Parkinson Disease and Movement Disorders Society, and American Academy of Neurology, outside of the submitted work. WGM reports personal fees from Lundbeck, Teva, Takeda, Alterity, Inhibikase, Servier, GE, and UCB; and grant support from Fondation de France, Michael J Fox Foundation, Multiple System Atrophy Coalition, Bordeaux Initiative for Neurodegenerative Disordes, Programme Hospitalier de Recherche Clinique, and Agence Nationale de la Recherche. EC declares no competing interests. GKW died in February, 2024.
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