Sleep Disturbance Associated with Severity and Death in Multiple System Atrophy

Background: Sleep-related breathing disturbances are common in multiple system atrophy (MSA) and may accelerate disease progression. We explored whether the burden of sleep-disordered breathing predicts disability and mortality in a well-characterised MSA cohort.Methods: We retrospectively reviewed 42 consecutive patients (21 women; mean ± SD age 60 ± 7 years) who underwent diagnostic polysomnography (PSG) within 12 months of meeting consensus criteria for probable MSA. Stridor, sleep apnoea/hypopnoea index (AHI), arousal index, and total sleep time were extracted from overnight PSG. Clinical severity was graded with the Unified MSA Rating Scale parts I + II (UMSARS-I+II). Survival status was ascertained through medical records and national mortality files. Cox proportional-hazard models, adjusted for age, sex, and phenotype (MSA-P vs MSA-C), quantified the association between PSG variables, disability, and all-cause death.Results: Over a median follow-up of 24 months (IQR 24–48), 31 of 42 patients (73.8%) died. Stridor was documented in 24 patients (57.1%). Compared with those without stridor, patients with stridor exhibited higher AHI (median 32 vs 18 events·h⁻¹, p = 0.013) and shorter total sleep time (305 ± 48 vs 342 ± 39 min, p = 0.002). In patients without stridor, severe sleep apnoea (AHI ≥ 30 events·h⁻¹) independently predicted death (hazard ratio [HR] 5.89, 95% CI 1.66–20.90, p = 0.006) after adjustment for UMSARS-I+II (HR 1.07 per point, 95% CI 1.02–1.12, p = 0.002). In those with stridor, higher arousal index was associated with improved survival (HR 0.94 per unit, 95% CI 0.90–0.99, p = 0.014).Conclusions: In early-stage MSA, severe sleep apnoea is a strong, independent marker for accelerated mortality only in patients without stridor, highlighting a potentially modifiable risk. Conversely, frequent micro-arousals appear protective in those with stridor, suggesting distinct pathophysiological mechanisms. Timely PSG and tailored management of sleep-disordered breathing may improve risk stratification and inform therapeutic trials in MSA.