Association Between REM Sleep Without Atonia and Multiple Sclerosis Subtypes: A Polysomnographic Study
Jad El Ahdab1, Daniel Ontaneda1, Tyler Bare1, Sikawat Thanaviratananich1, Kunio Nakamura1, Matheus Lima Diniz Araujo1, Scott Husak1, Julia O'Mahony2, James Bena1, Delaney Ryan1, Nancy Foldvary-Schaefer1
1Cleveland Clinic, 2The Hospital for Sick Children
Objective:

To investigate the association between REM sleep without atonia (RSWA) and multiple sclerosis (MS) and by progressive and non-progressive MS course.

Background:

REM sleep behavior disorder (RBD) is the earliest prodromal feature of the α-synucleinopathies. RSWA is the polysomnographic (PSG) biomarker of RBD. While RBD is more common in MS than general population estimates, precise measurements of RSWA in MS are lacking. We analyzed the relationship between MS diagnosis, disease course, and other clinical and MRI features with RSWA.

Design/Methods:

PSGs performed February 2023-August 2025 in patients with MS and matched controls (1:3) with at least 10 mins of REM sleep were scored for RSWA using chin and flexor-digitorum superficialis EMG including both tonic and phasic activity. RSWA was quantified using AASM v2.6 criteria. Epochs with respiratory events or arousals were excluded. MS patients were categorized as non-progressive or progressive. Wilcoxon rank-sum tests compared RSWA% between MS diagnosis adjusting for psychotropic use. Results are reported as median (IQR). Additional analyses assessed relationships between RSWA, motor performance, MRI volumetrics and lesion burden.

Results:

A total of 209 patients were included: 52 with MS (36 non-progressive; 16 progressive) and 157 controls. Mean age was 52.8±16.9 years; 78% were female. Progressive MS was associated with significantly higher RSWA vs. non-progressive MS and controls (p=0.014). Progressive MS exhibited a 317.5% higher RSWA% vs. controls (95% CI: 36.58-1176; p=0.012) and 298.7% vs non-progressive MS (95% CI:16.20%-1268%; p=0.028). Within the non-progressive group, RSWA correlated positively with right-hand motor task time (Spearman r=0.40, p=0.022). No consistent associations were observed between RSWA and quantitative MRI markers.

 

Conclusions:

Progressive MS is strongly associated with elevated RSWA. These findings suggest that RSWA and subsequentially RBD may reflect disease progression and neurodegenerative burden in MS with sparing in non-progressive MS, warranting further investigation into its clinical and prognostic significance.

10.1212/WNL.0000000000217445
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