Simultaneous tonic and phasic REM sleep without atonia best predicts early phenoconversion to neurodegenerative disease in idiopathic REM sleep behavior disorder

Abstract

Study Objectives Rapid eye movement (REM) sleep without atonia (RWA) is the main polysomnographic feature of idiopathic REM sleep behavior disorder (iRBD) and is considered to be a promising biomarker predicting conversion to manifested synucleinopathy. Besides conventionally evaluated tonic, phasic and any RWA, we took into consideration also periods, when phasic and tonic RWA appeared simultaneously and we called this activity “mixed RWA.” The study aimed to evaluate different types of RWA, to reveal the most relevant biomarker to the conversion. Methods A total of 55 patients with confirmed iRBD were recruited with mean follow-up duration 2.3 ± 0.7 years. Scoring of RWA was based on Sleep Innsbruck Barcelona rules. Positive phenocoversion was ascertained according to standard diagnostic criteria during follow-up. Receiver operator characteristic analysis was applied to evaluate predictive performance of different RWA types. Results A total of nine patients (16%) developed neurodegenerative diseases. Yearly phenoconversion rate was 5.5%. Significantly higher amounts of mixed (p = 0.009), tonic (p = 0.020), and any RWA (p = 0.049) were found in converters. Optimal cutoffs differentiating the prediction were 16.4% (sensitivity 88.9; specificity 69.6) for tonic, 4.4% (sensitivity 88.9; specificity 60.9) for mixed, and 36.8% (sensitivity 77.8; specificity 65.2) for any RWA. With area under the curve (AUC) 0.778, mixed RWA has proven to be the best predictive test followed by tonic (AUC 0.749) and any (AUC 0.710). Conclusions Mixed, tonic and any RWA may serve as biomarkers predicting the conversion into neurodegenerative disease in iRBD. The best predictive value lies within mixed RWA, thus it should be considered as standard biomarker.

REM Sleep Behavior Disorder as a Pathway to Dementia: If, When, How, What, and Why Should Physicians Disclose the Diagnosis and Risk for Dementia

“…Several other factors that are also linked to a prodromal state can improve the prediction of neurodegeneration. These include symptomatic orthostatic hypotension, olfactory dysfunction (by standardized testing), erectile dysfunction, hypersomnia, constipation, urinary dysfunction (typically urge incontinence), cognitive dysfunction, history of depression, diabetes, physical inactivity, and severity of RSWA [ 14 – 16 ]. Neuroimaging findings with predictive value include abnormal presynaptic tracer uptake (at least 2 standard deviations below the mean) on dopamine transporter SPECT or PET imaging and hyperechogenicity on ultrasound of the substantia nigra [ 17 ].…”

Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder

“…13,16 Similarly, REM sleep without atonia has been identified as one of earliest signs of neurodegeneration 17,18 and a valuable prognostic biomarker of disease progression, as it increases over time and greater severity is associated with accelerated phenoconversion. 19,20 One study limitation is the small sample size. However, relying on our current results, chromatic pupillometry abnormalities might be proposed as a further potential early marker of parasympathetic affection and/or of mRGC dysfunction in iRBD.…”

MIBG Cardiac Scintigraphy as a Potential Biomarker That Reflects Severity in Idiopathic REM Sleep Behavior Disorder

“…[43][44][45] Consequently, recent studies indicated that RWA may serve as a biomarker for neurodegenerative disease emerged from iRBD. 46,47 To the best of our knowledge, this is the rst study that demonstrated the lower HMR may predict higher RWA. In this study, we set the cut-off value within the iRBD group and showed the association between decreased MIBG uptake and RWA.…”