Evolution of Prodromal Multiple System Atrophy from REM Sleep Behavior Disorder: A Descriptive Study

Area of Science:

• Neurology
• Sleep Medicine
• Neurodegenerative Disorders

Background:

• Multiple System Atrophy (MSA) prodromal markers are poorly understood due to limited prospective studies.
• Retrospective analyses have primarily characterized the early stages of MSA.
• Direct observation of prodromal symptoms in MSA is scarce.

Purpose of the Study:

• To prospectively track and characterize prodromal markers in patients with idiopathic/isolated REM sleep behavior disorder (iRBD).
• To understand the evolution of motor, sleep, autonomic, and cognitive symptoms preceding MSA diagnosis.
• To compare phenoconversion pathways from iRBD to MSA versus other Lewy body diseases.

Main Methods:

• Annual comprehensive assessments of iRBD patients, including motor, sleep, psychiatric, and autonomic evaluations.
• Quantitative motor testing, neuropsychological assessments, and autonomic function tests (orthostatic blood pressure, olfaction, color vision).
• Comparison of patients who developed MSA with those who developed Parkinson's disease or dementia with Lewy bodies.

Main Results:

• Of 67 phenoconverters, 4 developed MSA with Parkinsonian features (MSA-P) and 63 developed other Lewy body diseases.
• MSA-P patients were younger, had less REM sleep atonia, more insomnia, and better olfaction than Lewy body disease patients.
• Autonomic dysfunction, particularly genitourinary issues, emerged late; olfaction and cognition remained largely preserved in prodromal MSA.

Conclusions:

• Prodromal MSA is characterized by rapid progression with minimal early autonomic dysfunction.
• Olfaction and cognitive functions are preserved throughout the prodromal phase of MSA.
• Idiopathic/isolated REM sleep behavior disorder serves as a valuable model for studying prodromal MSA.