Multiple System Atrophy: Advances in Diagnosis and Therapy

Abstract

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.

Keywords: KeywordsaaDisease-modifying therapy; Multiple system atrophy; Neuroinflammation; Oligodendrocyte; α-synuclein.

Figure 1.

Summary of the Movement Disorders Society criteria for the clinical diagnosis of multiple system atrophy. OH, orthostatic hypotension; RBD, REM sleep behavior disorders; VD; voiding difficulties; nOH, neurogenic orthostatic hypotension; AF, autonomic failure; RV, residual volume; MRI, magnetic resonance imaging.

Figure 2.

Proposed pathogenesis in MSA. Research on the characteristic structure of α-synuclein, neuroinflammation involvement, and the interaction between oligodendroglia and neurons is rapidly advancing progress in MSA. MSA, multiple system atrophy.

Figure 3.

A novel diagnostic marker in MSA. Diagnostic methods for MSA include the development of techniques to detect MSA-type α-synuclein and neurofilament light chain release with the loss of neurons and oligodendroglia, monitoring of characteristic laryngeal findings, and the development of imaging methods combining advanced statistical methods such as artificial intelligence, machine learning, and deep learning. MSA, multiple system atrophy; CSF, cerebrospinal fluid; PD, Parkinson’s disease.