An overview of the current management and emerging therapies of Multiple system atrophy

Multiple system atrophy is a sporadic α-synucleinopathy, characterized by parkinsonism, cerebellar and pyramidal signs combined in different ways, in association with autonomic failure. In absence of disease-modifying therapies, management is directed toward symptomatic treatment and maintenance of function.

This review critically appraises current evidence, highlights novel therapeutic strategies, and provides guidance for clinical practice and future research directions. A literature search without date restrictions was conducted using PubMed to identify published studies relevant to this review. Motor symptom interventions are primarily levodopa-based, yielding partial and transient responses, especially in MSA-P, whereas dopaminergic agonists, MAO-B inhibitors, amantadine, and device-aided therapies provide a limited or short-lived benefit. Physiotherapy, occupational therapy, and multidisciplinary rehabilitation are integral to motor symptoms management. Non-motor symptoms management target autonomic failure (neurogenic orthostatic hypotension, urinary/sexual dysfunction, etc.), gastrointestinal dysmotility and sleep disorders (REM sleep Behavior Disorder, stridor, etc.), using a stepwise combination of lifestyle measures, pharmacological agents and device-aided interventions.

Management of MSA remains largely symptomatic. Multimodal treatment and integration of rehabilitative and non-pharmacological strategies are critical, while ongoing trials in neuroprotection and neuromodulation represent key avenues to improve long-term outcomes.