Tippmann‐Peikert, Maja

Abstract Introduction While REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) is associated with male sex, age greater than or equal to 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/persistent periodic limb movements of sleep in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities, and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations, we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy, and RSWA/non-PLMS-REM, we identified 27 patients. All in-lab polysomnograms (PSGs) were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a control group of 15 individuals without RSWA, reviewed their PSGs, and calculated the REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64 +/- 8.3 (standard error of mean (SEM)) per hour versus 1 +/- 0.6 (SEM) per hour in non-RSWA controls (p < 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/- 3 (SEM) years and 81% versus 87% men, respectively. However, psychiatric diagnosis, neurological disorders, and antidepressants use were more common among RSWA/PLMS-REM patients compared to non-RSWA controls with p = 0.0002, p = 0.0035 and p = 0.0074 respectively (Fisher’s Exact Test). Conclusion Psychiatric diagnosis, neurological disorders, and antidepressant use are more common among RSWA/PLMS-REM patients compared to non-RSWA/non-PLMS-REM controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):

Abstract Introduction While RSWA in REM sleep behavior disorder (RBD) is associated with male sex, age > 50 years, alpha-synucleinopathies, and narcolepsy, the characteristics of patients with RSWA/PLMS in REM sleep (RSWA/PLMS-REM) without dream enactment behaviors are unexplored. The aim of this study was to compare the demographics, comorbidities and concomitant medication use between RSWA/PLMS-REM patients and non-RSWA/non-PLMS-REM controls. Based on anecdotal clinical observations we hypothesized that these patients are more commonly young, women, have psychiatric or neurological diseases, and use antidepressants. Methods We conducted a retrospective review of the Mayo Clinic electronic medical record to identify all patients with RSWA/ PLMS-REM between November 2018 and November 2020. After excluding all patients with RBD, restless legs syndrome, narcolepsy and RSWA/non-PLMS-REM we identified 27 patients. All PSGs were reviewed to calculate the periodic limb movement index per hour of REM sleep (REM-PLMI). We also identified a covenience sample of 15 non-RSWA controls, reviewed their PSGs and calculated REM-PLMI. Results The mean REM-PLMI of patients with RSWA was 64+/-8.3 (SEM)/hour versus 1+/-0.6 (SEM)/hours in non-RSWA controls (p< 0.001). Patients with RSWA/PLMS-REM and non-RSWA controls had similar age and gender, 62 +/- 3 (SEM) versus 58 +/-3 (SEM) years and 81% versus 87% men, respectively. However psychiatric diagnosis, neurological disorders and antidepressants use was more common among RSWA/PLMS-REM patients compared to non-RSWA controls, p=0.0002, p=0.0035 and p=0.0074, respectively. (Fisher’s Exact Test) Conclusion Psychiatric diagnosis, neurological disorders and antidepressant use are more common among RSWA/PLM-REM patients compared to non-RSWA controls. Further research to determine the implications of a diagnosis of RSWA/PLMS-REM for the future development of alpha-synucleinopathies are needed and currently ongoing. Support (if any):

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):