Early onset sleep disorders predict severity, progression and death in multiple system atrophy

Area of Science:

• Neurology
• Sleep Medicine
• Neurodegenerative Diseases

Background:

• Early stridor onset (≤3 years) predicts shorter survival in Multiple System Atrophy (MSA).
• The impact of stridor and REM sleep behavior disorder (RBD) on MSA disease progression remains unclear.
• Previous MSA progression studies have not incorporated stridor and RBD as variables.

Purpose of the Study:

• To investigate disease progression in MSA patients with early stridor onset and early stridor and/or RBD onset.
• To evaluate cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) levels in MSA patients with early-onset sleep disorders.

Main Methods:

• Retrospective and prospective cohort study of 208 MSA patients.
• Video-polysomnography (VPSG)-confirmed RBD and stridor.
• Analysis of CSF NfL levels, disease milestones, and survival data.

Main Results:

• Patients with early stridor and/or RBD onset exhibited earlier autonomic involvement, more severe disease, and higher CSF NfL levels.
• Early stridor and early RBD were identified as independent risk factors for MSA survival.
• Out of 208 patients, 91 had stridor and 160 had VPSG-confirmed RBD.

Conclusions:

• Early development of sleep disorders (stridor, RBD) in MSA is associated with more rapid disease progression.
• Elevated CSF NfL levels in these patients suggest widespread central nervous system impairment.
• These findings may define a distinct MSA phenotype characterized by early and severe brainstem circuit involvement.