Gossard, Thomas

Abstract Study Objectives Post-traumatic stress disorder (PTSD) and rapid eye movement (REM) sleep behavior disorder (RBD) share some common features including prominent nightmares and sleep disturbances. We aimed to comparatively analyze REM sleep without atonia (RSWA) between patients with chronic PTSD with and without dream enactment behavior (DEB), isolated RBD (iRBD), and controls. Methods In this retrospective study, we comparatively analyzed 18 PTSD with DEB (PTSD+DEB), 18 PTSD without DEB, 15 iRBD, and 51 controls matched for age and sex. We reviewed medical records to determine PTSD clinical features and quantitatively analyzed RSWA. We used nonparametric analyses to compare clinical and polysomnographic features. Results PTSD patients, both with and without DEB, had significantly higher RSWA than controls (all p < .025, excepting submentalis phasic duration in PTSD+DEB). Most RSWA measures were also higher in PTSD+DEB than in PTSD without DEB patients (all p < .025). Conclusions PTSD patients have higher RSWA than controls, whether DEB is present or not, indicating that REM sleep atonia control is abnormal in chronic PTSD. Further prospective studies are needed to determine whether neurodegenerative risk and disease markers similar to RBD might occur in PTSD patients.

Abstract Introduction REM sleep behavior disorder (RBD) is characterized by disruptive, violent dream enactment behaviors (DEB), necessitating symptomatic treatment to prevent injury and reduce DEB frequency and severity. Melatonin and clonazepam are regarded as RBD therapeutic mainstays, although outcomes data remains limited. We surveyed RBD patients to determine their outcomes following melatonin, clonazepam, and melatonin-clonazepam combination therapy. Methods Mayo Clinic RBD Patient Registry participants received an electronic survey concerning treatment type(s) and dose(s), efficacy, and adverse effects. The primary outcome was treatment efficacy, determined by comparing DEB frequency/severity ratings on a visual analog scale (VAS). Adverse effects severity was assessed by Likert scales. We comparatively analyzed VAS before and after treatment and adverse effects between treatments using non-parametric statistical tests. Results Sixty-eight of 109 patients responded (62.3%; 64 had analyzable data) with a mean age of 67.7 years. Fifty-seven (85%) were men, with mean RBD symptom duration of 13.9 years. Patients receiving each treatment were: melatonin=30, clonazepam=8, and combination=12; 14 received other or no treatment. Baseline VAS ratings were similar between groups. Only melatonin (p=0.003) and combination therapy (p=0.039) improved VAS ratings; clonazepam monotherapy did not improve VAS. Only melatonin monotherapy was reported to lower VAS compared to untreated patients (p=0.02). Optimally effective mean dosages were melatonin 9.95±5.06 mg and clonazepam 0.81±0.48 mg. Patient frequencies reporting one or more moderately-severe side effect(s) were similar between melatonin (15%), clonazepam (7%), and combination therapies (9%). Twenty-five (36.8%) patients had received only one medication trial, while 41.2% required more than one medication. Of these, 15 (22.1%) tried 2 and 13 (19.1%) tried 3 or more treatments. Conclusion Melatonin therapy at an approximate mean 10 mg dosage improved patient-reported DEB frequency/severity on VAS, compared between both previous intraindividual baseline ratings and with untreated patients, while clonazepam monotherapy did not, without differential adverse effects. Clonazepam monotherapy data were limited. These data inform future prospective melatonin symptomatic therapy trials for RBD. Additionally, 41.2% required more than one RBD pharmacological treatment, suggesting a current therapeutic gap and unmet need for future development of biologically-informed, evidence-based symptomatic RBD therapeutics. Support (if any):

ABSTRACTBackgroundRapid eye movement (REM) sleep behavior disorder (RBD) occurs occasionally in essential tremor (ET), but polysomnographic REM sleep without atonia (RSWA) analyses have been sparse.ObjectiveTo characterize the amount and distribution of polysomnographic RSWA, the electrophysiologic substrate of RBD, in patients with Parkinson's disease (PD) and ET.MethodsWe analyzed quantitative RSWA in 73 patients: PD (23), ET (23), and age‐sex‐matched controls (27). None had dream‐enactment behavior history or received antidepressants. Phasic, tonic, “any,” and phasic‐burst duration RSWA measures were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index (RAI) was also determined. Statistical analysis was performed by Kruskal‐Wallis rank‐sum and Mann‐Whitney tests.ResultsSM phasic RSWA was significantly greater for PD than ET patients and controls (12.5% ± 12.8% vs. 4.9% ± 6.7%, 3.9% ± 2.6%), as was SM “any” (13.54% ± 14.30% vs. 5.2% ± 7.6%, 4.2% ± 2.6%). RAI was significantly lower in PD than in ET and controls (0.78 ± 0.23 vs. 0.92 ± 0.09 vs. 0.90 ± 0.17, P ≤ 0.005), but no different between ET and controls. AT phasic and “any” RSWA was similar between the 3 groups. ET and control RSWA was similar in all measures. Two ET patients (8.7%) had SM RSWA similar to PD patients.ConclusionsElevated SM RSWA distinguished PD from ET in patients without dream‐enactment symptoms and occurs frequently in PD patients, and in isolated tremor suggests underlying synucleinopathy. Prospective studies will further validate these findings.

Abstract Introduction Post-traumatic stress disorder (PTSD) is characterized by persistent mental and emotional stress following one or more significant physical or psychological traumatic incidents earlier in life. Vivid recall of the events, including traumatic nightmares, and prominent sleep disturbance are usual in PTSD. Previous studies have suggested that PTSD may share some clinical features with idiopathic REM sleep behavior disorder (iRBD) including altered REM sleep without atonia (RSWA) levels. Our group has previously found evidence for altered RSWA control in patients with psychiatric disease, including a pilot sample of PTSD patients with iRBD. We aimed to comparatively analyze RSWA levels between patients with PTSD, PTSD and RBD (PTSD+RBD), iRBD, and controls. Methods We selected 18 PTSD, 18 PTSD+RBD, 15 iRBD, and 51 healthy control patients matched for age and sex from the Mayo Clinic Center for Sleep Medicine’s polysomnography database for RSWA quantification. RSWA amounts in the submentalis (SM) and anterior tibialis (AT) were quantitatively analyzed as a percentage of REM sleep duration, in accordance with previously published methods. Non-parametric analyses were performed to compare RSWA, patient demographics, and PSG data across groups. Significance was set at p < 0.016. Results Patients with PTSD had significantly higher RSWA than controls in all RSWA density measures (p < 0.016 for all). All measures of RSWA, excluding average SM duration, were significantly greater in PTSD+RBD patients compared with controls (p < 0.016 for all). Within the PTSD group, patients on antidepressants did not have significantly higher RSWA in any of the measures. PTSD+RBD patients had significantly higher SM Phasic, AT Any, SM+AT Any, and Tonic RSWA measures than PTSD patients (p < 0.016 for all). Conclusion PTSD patients have significantly higher RSWA than controls, with PTSD+RBD patients having higher RSWA levels than PTSD patients. These data provide the first evidence for abnormal RSWA control in patients with chronic PTSD. This provides evidence of a unique biology in PTSD that could imply a future risk for neurodegenerative disease in PTSD similar to RBD patients. Further prospective studying will need to be performed on patients with PTSD to understand the unique biology. Support

Abstract Study Objectives Values for normative REM sleep without atonia (RSWA) remain unclear. Older age and male sex are associated with greater RSWA, and isolated elevated RSWA has been reported. We aimed to describe normative RSWA and characterize isolated RSWA frequency in adults without REM sleep behavior disorder (RBD). Methods We visually quantified phasic, “any,” and tonic RSWA in the submentalis (SM) and anterior tibialis (AT) muscles, and the automated Ferri REM Atonia Index during polysomnography in adults without RBD aged 21–88. We calculated RSWA percentiles across age and sex deciles and compared RSWA in older (≥ 65) versus younger (<65) men and women. Isolated RSWA (exceeding diagnostic RBD cutoffs, or >95th percentile) frequency was also determined. Results Overall, 95th percentile RSWA percentages were SM phasic, any, tonic = 8.6%, 9.1%, 0.99%; AT phasic and “any” = 17.0%; combined SM/AT phasic, “any” = 22.3%, 25.5%; and RAI = 0.85. Most phasic RSWA burst durations were ≤1.0 s (85th percentiles: SM = 1.07, AT = 0.86 seconds). Older men had significantly higher AT RSWA than older women and younger patients (all p < 0.04). Twenty-nine (25%, 18 men) had RSWA exceeding the cohort 95th percentile, while 17 (14%, 12 men) fulfilled diagnostic cutoffs for phasic or automated RBD RSWA thresholds. Conclusions RSWA levels are highest in older men, mirroring the demographic characteristics of RBD, suggesting that older men frequently have altered REM sleep atonia control. These data establish normative adult RSWA values and thresholds for determination of isolated RSWA elevation, potentially aiding RBD diagnosis and discussions concerning incidental RSWA in clinical sleep medicine practice.