PT  - JOURNAL ARTICLE
AU  - Liu, Yaping
AU  - Zhang, Jihui
AU  - Chau, Steven WH
AU  - Man Yu, Mandy Wai
AU  - Chan, Ngan Yin
AU  - Chan, Joey WY
AU  - Li, Shirley Xin
AU  - Huang, Bei
AU  - Wang, Jing
AU  - FENG, Hongliang
AU  - Zhou, Li
AU  - Mok, Vincent
AU  - Wing, Yun kwok
TI  - Evolution of Prodromal REM Sleep Behavior Disorder to Neurodegeneration: A Retrospective, Longitudinal Case-control Study
AID  - 10.1212/WNL.0000000000200707
DP  - 2022 May 12
TA  - Neurology
PG  - 10.1212/WNL.0000000000200707
4099  - http://n.neurology.org/content/early/2022/05/12/WNL.0000000000200707.short
4100  - http://n.neurology.org/content/early/2022/05/12/WNL.0000000000200707.full
AB  - Background and Objectives: Individuals with a history of recurrent dream-enactment behaviors, but with subthreshold REM sleep without atonia levels for REM sleep behavior disorder (RBD) diagnosis, are currently classified to have prodromal RBD (pRBD). However, the REM sleep elevated EMG diagnostic cut-off, progression trajectory, and long-term neurodegenerative outcome of pRBD are not well understood. This study aimed to delineate the evolution of REM sleep EMG levels, determine the EMG cut-off score for diagnosing pRBD, and examine the risk for neurodegenerative diseases of pRBD.Methods: This retrospective longitudinal case-control study recruited pRBD patients and age, sex, and follow-up duration matched controls who were free of neurodegenerative disease at baseline in the Sleep Assessment Unit, the Chinese University of Hong Kong from 1997 to 2018. Patients and controls underwent clinical and video-polysomnography assessments at baseline and follow-up(s). REM sleep EMG activity level on mentalis and anterior tibialis (AT) muscles on video-polysomnography at each visit was scored. The diagnosis of neurodegenerative diseases was confirmed by a neurologist.Results: 44 patients (67.4 ± 8.2 years old, 6 females) and 44 controls were recruited. The combined REM sleep EMG level on mentalis and AT muscles of pRBD patients significantly increased during 8.2 ± 3.3 years of follow-up (from 19.3 ± 9.7% to 47.3 ± 27.4% with estimated annual increase of 3.9%), yielding 29 pRBD patients (66%) meeting the full-blown RBD diagnostic criteria. Baseline REM sleep mentalis and AT muscles EMG activity of patients who developed full-blown RBD could favourably differentiate pRBD from controls (6.3% for mentalis ‘any’ and 9.1% for combination of mentalis ‘any’ and bilateral AT muscles phasic EMG with AUC of 0.88 [0.78-0.98] and 0.97 [0.92-1.00] respectively). pRBD patients had a higher risk for neurodegenerative diseases (9 developed Parkinson’s disease and 3 developed dementia with Lewy bodies) when compared to controls (5 developed Alzheimer’s disease, adjusted hazard ratio = 2.95, 95% CI = 1.02-8.54).Conclusions: pRBD has a predictive progression in both pathophysiology and neurodegenerative outcome. This finding has significant implications to the nosological status of pRBD, the current REM sleep-related EMG diagnostic criteria, spectrum concept of RBD and future neuroprotective intervention.Classification of Evidence: This study provides Class III evidence that EMG activity during REM sleep predicts the development of prodromal REM sleep behavior disorder.