Bibi, Noor

Abstract Study Objectives Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. Methods One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. Results Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. Conclusions Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients’ values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

Abstract Introduction Accurate, early diagnosis of isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is crucial given its injury potential and neurological prognosis. We aimed to analyze visual and automated REM sleep without atonia (RSWA) diagnostic thresholds in a current cohort of iRBD patients using submentalis (SM) and individual four limb electromyography (EMG) recordings, including bilateral flexor digitorum superificialis (FDS) and anterior tibialis (AT) during polysomnography. Methods We analyzed RSWA in 20 iRBD patients and 20 age-sex-AHI matched controls who underwent polysomnography between 2017-2021 for phasic burst durations, phasic, tonic, and "any" muscle activity, and automated REM atonia index (RAI). Group RSWA metrics were analyzed with non-parametric comparisons, logistic regression, and receiver operating characteristic (ROC) curves to determine optimal diagnostic cutoff thresholds for iRBD. Correlation explored associative relationships between RSWA metrics, and principal components analysis (PCA) defined determinants of RSWA metric variance. Results All mean RSWA metrics were higher in iRBD patients than controls (p<0.05), except for left and bilateral AT phasic density and duration. RSWA(phasic%, AUC; "any"%, AUC) cutoffs were: SM (6.5%, AUC=90.2; 6.5%, AUC=92.5); L FDS (7.3%, AUC=95.8; 7.3%, AUC=95.8%); R FDS (5.4%, AUC=93.5; 5.8%, AUC=93.2%); Bilateral FDS (10.7%, AUC=96; 15.3%, AUC=95.8); L AT (6.7%, AUC=74.5; 6.7%, AUC=74.8%); R AT (4.7%, AUC=76.8; 4.7%, AUC=76.8%); Bilateral AT (7.5%, AUC=77.5; 7.5%, AUC=77.5%), combined SM/FDS (15.0%, AUC=95.5; 15.1%; AUC=95.8), combined SM/AT (16.5%, AUC=85.8; 21.0%; AUC=88.8),tonic (0.5%; AUC=85.9), and RAI (0.90; AUC=91.4). Phasic burst duration cutoffs were: SM=0.7s (AUC=90.2), L FDS=0.5 s (AUC=83.2), R FDS=0.6 (AUC=85.2), L AT=0.3 s (AUC=65.0) and R AT=0.4 s (AUC=77.0). PCA demonstrated that FDS and combined SM/FDS and SM/AT RSWA metrics best explained RSWA variance and differentiated controls from RBD, while SM and AT alone were less explanatory. Conclusion This study provides evidence for quantitative RSWA diagnostic thresholds applicable in current iRBD populations, and confirms the key importance of FDS to assure accurate iRBD diagnosis. Interestingly, these RSWA diagnostic thresholds are lower than previously determined thresholds, suggesting secular trends toward earlier iRBD detection and heterogeneous disease duration relative to polysomnography acquisition, underscoring the necessity of future large scale prospective, multicenter polysomnographic analyses to determine definitive iRBD diagnostic RSWA thresholds. Support (If Any)

Abstract Introduction REM sleep without atonia (RSWA) is the neurophysiological substrate of REM sleep behavior disorder (RBD), a form of prodromal parkinsonism in most older adults. Isolated RSWA (without clinical RBD) elevation was demonstrated recently in older adults following SARS-CoV2 (COVID-19) infection, but comparison to controls was not reported. We aimed to comparatively analyze RSWA between patients with previous COVID-19 infection and COVID-19 negative controls. Methods 25 patients with previous COVID-19 infection were compared to 25 age-sex matched controls who tested negative for COVID-19 prior to polysomnography. Patients receiving medications known to increase RSWA were excluded. We reviewed medical records to determine clinical features and quantitatively analyzed RSWA in the submentalis (SM) and anterior tibialis (AT) muscles for phasic, tonic, and “any” muscle activity, phasic burst duration, and the automated REM atonia index. Non-parametric analyses compared clinical and polysomnographic features between groups, with combined SM and AT RSWA as the defined primary outcome. The comparative frequency of COVID-19 positive cases and COVID-19 negative controls who met or exceeded proposed isolated RSWA thresholds was also determined. Results COVID-19 patients had significantly greater RSWA than COVID-19 negative controls in the combined SM and AT muscles (p = 0.00076). Most other RSWA metrics were also higher in COVID-19 patients than controls (p<0.03), except tonic muscle activity, phasic burst durations, and RAI. Isolated RSWA occurred more frequently in COVID-19 (9 patients, 36%) than controls (3, 12%; p>0.05). No patients had a clinical history or polysomnographic evidence for parasomnia behavior or a primary neurological condition. Conclusion Quantitative RSWA amounts were comparatively greater in COVID-19 patients than in COVID-19 tested-negative controls, suggesting association of previous COVID-19 infection with central nervous system brainstem dysfunction in the region of the dorsal pons and/or ventromedial medulla. Further prospective studies are needed to determine whether RSWA is a predisposing influence to, or consequence of, COVID-19 infection in these patients, and whether COVID-19 survivors might harbor neurodegenerative risk or disease markers. Support (If Any)