Assistant Attending Neurologist, NewYork-Presbyterian Hospital, and Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Barone reports he is on the speakers bureau for Jazz Pharmaceuticals and is a consultant for Molecule Mattress.
SYNOPSIS: Objective findings during polysomnography (REM sleep without atonia), as diagnosed with submentalis EMG recordings, may be a biomarker for synucleinopathies, such as Parkinson’s disease and multiple system atrophy.
SOURCE: McCarter SJ, Feemster JC, Tabatabai GM, et al. Submentalis rapid eye movement sleep muscle activity: A potential biomarker for synucleinopathy. Ann Neurol 2019;86:969-974.
Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), grouped as “parkinsonism” syndromes, often have overlapping symptoms, which can complicate diagnosis. This is unfortunate because the prediction of treatment response, prognostic counseling, and use of disease-modifying therapy rely on such accuracy. Currently, diagnosis of parkinsonism is based on clinical evaluation with limited biomarkers.
Tau accumulation is associated with PSP and CBD (so-called tauopathies), whereas alpha-synuclein accumulation is associated with PD and MSA (so-called synucleinopathies). Rapid eye movement (REM) sleep behavior disorder (RBD) consists of a history of dream enactment behavior (DEB) in conjunction with REM sleep without atonia (RSWA) noted during polysomnography (PSG) testing. RBD strongly correlates with alpha-synucleinopathy, but much less with tauopathies. Despite this clear difference, clinical DEB is not specific for parkinsonism etiology. Thus, the authors aimed to determine whether quantitative RSWA testing distinguishes probable synucleinopathy and tauopathy subtypes of parkinsonism, using electromyographic (EMG) analysis in the submentalis and anterior tibialis muscles in parkinsonian patients.
The authors analyzed RSWA in 97 patients at the Mayo Clinic between 2008 and 2015. Patient groups included 53 probable synucleinopathy patients (meeting clinical diagnostic criteria for PD [n = 33] and MSA [n = 20]) and 24 probable tauopathy patients (meeting clinical criteria for PSP [n = 17] or CBD [n = 7]). These groups were analyzed against 20 age- and sex-matched controls. Of note, while both visual scoring (by standard American Academy of Sleep Medicine standards) and automated scoring (via HypnoLab software) were used and compared, the automated scoring method demonstrated more cases of RSWA and was more precise in that it allowed for a REM atonia index (RAI).
Comparing RAI across the four parkinsonian conditions, elevated submentalis EMG activity was highly sensitive (70-77%) and specific (95-100%) in distinguishing synucleinopathy from tauopathy, whereas with anterior tibialis EMG, synucleinopathy discrimination was poor. The authors concluded that elevated submentalis EMG activity in RSWA appears to be a potentially useful biomarker for presumed synucleinopathy etiologies in parkinsonism.
With this paper, the authors have opened a new door for further research into RSWA and RBD, an ever-growing subset of neurology and sleep medicine. The authors mentioned that among the 97 patients, the use of quantitative scoring demonstrated more cases of RSWA than qualitative scoring by visual inspection, and there was poor correlation between the quantitative and qualitative methods. This is important, as often in clinical practice, RSWA typically is scored through visual inspection and thus, per this study, may be missed. Perhaps in the future, automated/universal scoring of EMG (especially in REM sleep) will allow for more uniform data analysis, with positive implications for both clinical and research endeavors.
Another element worth discussing is that in clinical practice, isolated RSWA without DEB is considered a PSG finding of unclear significance. The authors compared RSWA in cases both with and without DEB, and found the association that RSWA can distinguish synucleinopathy from tauopathy regardless of DEB. This finding adds to the growing literature that suggests that isolated RSWA may be a harbinger of synucleinopathy and requires further investigation.