Citations

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 Study Objectives To analyze cognitive deficits leading to unsafe driving in patients with REM Sleep Behavior Disorder (RBD), strongly associated with cognitive impairment and synucleinopathy-related neurodegeneration. Methods Twenty isolated RBD (iRBD), 10 symptomatic RBD (sRBD), and 20 age- and education-matched controls participated in a prospective case-control driving simulation study. Group mean differences were compared with correlations between cognitive and driving safety measures. Results iRBD and sRBD patients were more cognitively impaired than controls in global neurocognitive functioning, processing speeds, visuospatial attention, and distractibility (p < .05). sRBD patients drove slower with more collisions than iRBD patients and controls (p < .05), required more warnings, and had greater difficulty following and matching speed of a lead car during simulated car-following tasks (p < .05). Driving safety measures were similar between iRBD patients and controls. Slower psychomotor speed correlated with more off-road accidents (r = 0.65) while processing speed (−0.88), executive function (−0.90), and visuospatial impairment (0.74) correlated with safety warnings in sRBD patients. Slower stimulus recognition was associated with more signal-light (0.64) and stop-sign (0.56) infractions in iRBD patients. Conclusions iRBD and sRBD patients have greater selective cognitive impairments than controls, particularly visuospatial abilities and processing speed. sRBD patients exhibited unsafe driving behaviors, associated with processing speed, visuospatial awareness, and attentional impairments. Our results suggest that iRBD patients have similar driving-simulator performance as healthy controls but that driving capabilities regress as RBD progresses to symptomatic RBD with overt signs of cognitive, autonomic, and motor impairment. Longitudinal studies with serial driving simulator evaluations and objective on-road driving performance are needed.

AbstractStudy ObjectivesRapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disturbances are frequent in leucine-rich, glioma inactivated protein 1-IgG (LGI1) and contactin-associated protein 2-IgG (CASPR2) autoimmunity, yet polysomnographic analyses of these disorders remain limited. We aimed to characterize clinical presentations and analyze polysomnographic manifestations, especially quantitative REM sleep without atonia (RSWA) in LGI1/CASPR2-IgG seropositive (LGI/CASPR2+) patients.MethodsWe retrospectively analyzed clinical and polysomnographic features and quantitative RSWA between LGI1+/CASPR2+ patients and age-sex matched controls. Groups were compared with Wilcoxon rank-sum and chi-square tests. Combined submentalis and anterior tibialis (SM + AT) RSWA was the primary outcome.ResultsAmong 11 (LGI1+, n = 9; CASPR2+, n = 2) patients, Morvan syndrome sleep features were present in seven (63.6%) LGI1+/CASPR2+ patients, with simultaneous insomnia and dream enactment behavior (DEB) in three (27.3%), and the most common presenting sleep disturbances were DEB (n = 5), insomnia (n = 5), and sleep apnea (n = 8; median apnea-hypopnea index = 15/hour). Median Epworth Sleepiness Scale was nine (range 3–24; n = 10), with hypersomnia in four (36.4%). LGI1+/CASPR2+ patients had increased N1 sleep (p = .02), decreased REM sleep (p = .001), and higher levels of SM + AT any RSWA (p < .001). Eight of nine (89%) LGI1+ exceeded RBD RSWA thresholds (DEB, n = 5; isolated RSWA, n = 3). RSWA was greater in AT than SM. All 10 LGI1+/CASPR2+ patients treated with immunotherapy benefitted, and 5/10 had improved sleep disturbances.ConclusionsLGI1/CASPR2-IgG autoimmunity is associated with prominent dream enactment, insomnia, RSWA, sleep apnea, and shallower sleep. Polysomnography provides objective disease markers in LGI1+/CASPR2+ autoimmunity and immunotherapy may benefit associated sleep disturbances.

AbstractRoom tilt illusion is a rare phenomenon in which a person transiently perceives the surrounding environment as tilted to one side. Epilepsy is one of the presumed causes of room tilt illusion, but this has never been proven. We present a case of room tilt illusion that is epileptic in nature, documented by video‐ EEG monitoring. Our Patient is a 30‐year‐old woman with 11 years history of bi‐monthly spells of sudden tilt of the whole environment counterclockwise for a duration of one to two seconds. These spells were initially diagnosed as psychogenic. She was then admitted to our video‐EEG monitoring unit. She had three of her typical spells during monitoring, with corresponding changes of brief generalized spike‐wave burst on EEG that coincided temporarily with her symptoms. The video otherwise did not reveal any sway or tilt of the patient herself. She was started on topiramate with resolution of her symptoms. She remained spell‐free when seen during follow‐up, six months later. This case illustrates a first example of room tilt illusion that is documented to be epileptic in nature. This case adds to the varied nature of how epilepsy can manifest in patients, which may support improved diagnosis and treatment of epileptic patients.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2 . Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A ; postmortem whole exome sequencing identified 18 ultrarare variants.

Abstract Video-polysomnography (v-PSG) is essential for diagnosing rapid eye movement (REM) sleep behavior disorder (RBD). Although there are current American Academy of Sleep Medicine standards to diagnose RBD, several aspects need to be addressed to achieve harmonization across sleep centers. Prodromal RBD is a stage in which symptoms and signs of evolving RBD are present, but do not yet meet established diagnostic criteria for RBD. However, the boundary between prodromal and definite RBD is still unclear. As a common effort of the Neurophysiology Working Group of the International RBD Study Group, this manuscript addresses the need for comprehensive and unambiguous v-PSG recommendations to diagnose RBD and identify prodromal RBD. These include: (1) standardized v-PSG technical settings; (2) specific considerations for REM sleep scoring; (3) harmonized methods for scoring REM sleep without atonia; (4) consistent methods to analyze video and audio recorded during v-PSGs and to classify movements and vocalizations; (5) clear v-PSG guidelines to diagnose RBD and identify prodromal RBD. Each section follows a common template: The current recommendations and methods are presented, their limitations are outlined, and new recommendations are described. Finally, future directions are presented. These v-PSG recommendations are intended for both practicing clinicians and researchers. Classification and quantification of motor events, RBD episodes, and vocalizations are however intended for research purposes only. These v-PSG guidelines will allow collection of homogeneous data, providing objective v-PSG measures and making future harmonized multicentric studies and clinical trials possible.

Abstract Purpose Compare agreements between polysomnography-based (PSG) diagnosis of isolated REM-sleep-behavior-disorder (iRBD) and Non-REM-Hypertonia (NRH), a novel biomarker independently associated with synucleinopathy-related neurodegenerative diseases. Methods Sixteen patients with histories of dream-enactment-behavior (DEB)(women=38%; age:64.6±13.0) underwent PSG with simultaneously-recorded Sleep Profiler (SP). Two boarded sleep neurologists independently characterized iRBD. Physician1 combined abnormal qualitative REM-sleep-without-atonia (RSWA) by submental electromyography, with video-confirmation of probably DEB. Physician2 relied solely on qualitative RSWA. SP was auto-staged, technically reviewed, and reprocessed for automated abnormal NRH detection. Kappa scores measured physician and NRH agreements. Results In the 14 records with REM sleep, iRBD was characterized in: Physician1=64%, Physician2=79%, NRH=71% of the records. Across the three methods, unanimous iRBD agreement occurred in 57% of the records (positive=7, negative=1). The between-physician agreement in iRBD classifications was fair (kappa=0.32). The agreement between NRH and Physician1 was moderate (kappa=0.52) versus slight with Physician2 (kappa=0.05). NRH comparisons to consensus physician agreement yielded one false-positive and one false-negative iRBD finding. Physician2 classified: a) iRBD in two cases that were negative by Physician1 and NRH, and b) one negative case that Physician1 and NRH characterized as iRBD. Physician1 identified one negative case that was classified iRBD by Physician2 and NRH. Additionally, NRH was abnormal in one of the two records with no REM sleep. Discussion NRH may assist in iRBD risk assessment, given it agreed with at least one physician in 86% of the cases and the between-physician iRBD agreement was only fair. NRH also characterized iRBD-risk in patients with insufficient REM sleep for RSWA assessment.

Abstract Purpose Evaluate the sleep staging agreement between polysomnography (PSG) and Sleep Profiler (SP) in patients with suspected isolated REM-sleep-behavior-disorder. Methods Twenty-six patients with reported dream-enactment-behavior (Site1=16, Site2=10; 27% women; age 64±13 years) underwent a diagnostic PSG with simultaneously recorded SP. A registered sleep-technologist at each site performed PSG-staging, while SP was auto-staged and technically reviewed/edited. Across technicians, the initial staging was blinded. Site1 then performed unblinded restaging of PSG=N3(N2) vs. SP=N2(N3) epochs, while Site2 conducted a blinded, carefully-targeted restaging of N3. Statistics included Cohen’s kappa and Chi-square analyses. Results Agreement between SP and Site1 vs. Site2 were significantly different for Wake (kappa:Site1=0.816;Site2=0.650;combined=0.736), stage N1 (kappa:Site1=0.149;Site2=0.228;combined=0.188), stage N2 (kappa:Site1=0.632;Site2=0.718;combined=0.659), stage N3 (kappa:Site1=0.715;Site2=0.368;combined=0.525) and REM (kappa:Site1=0.827;Site2=0.719;combined=0.766)(all P<0.001). After restaging of N3, the kappa values improved at Site1 (unblinded:N2=0.659/N3=0.883) and Site2 (blinded:N2=0.775/N3=0.736)(combined:N2=0.735/N3=0.851). The proportion of PSG-epochs restaged from N3 to N2 was 17% at Sites1 and 38% at Site2 (P<0.001), while Site1 had fewer remaining PSG=N3 vs. SP=N2 conflicts (5.6% vs. 20.8%, P<0.001). Compared to Site2, Site1 had a superior: REM kappa due to fewer SP=N2 disagreements (8.5% vs. 16.8%, P<0.001), and Wake kappa resulting from fewer SP=N1 (6.6 vs. 15.6%, P<0.001) and SP=N2 conflicts (5.9 vs. 12.0%, P<0.001). Conversely, the Site1 N1 kappa was inferior due to greater SP=wake disagreement (41.6% vs. 19.8%, P<0.001). Discussion N3 was excessively stage by both PSG technicians before restaging. At Site1, Wake, N3, and REM had almost-perfect-agreement with SP, while N2 had substantial-agreement. At Site2 and across-site, substantial-agreement was observed for Wake, N2, N3, and REM.

Although insufficient sleep is associated with increased cardiovascular risk, evidence of a causal relationship is lacking. We investigated the effects of prolonged sleep restriction on 24-hour ambulatory blood pressure (BP) and other cardiovascular measures in 20 healthy young participants (aged 23.4±4.8 years, 9 females), who underwent a randomized, controlled, crossover, 16-day inpatient study consisting of 4 days of acclimation, 9 days of sleep restriction (4 hours of sleep/night) or control sleep (9 hours), and 3 days of recovery. Subjects consumed a weight maintenance diet with controlled nutrient composition throughout. A 24-hour BP (primary outcome) and cardiovascular biomarkers were measured repeatedly. Polysomnographic monitoring was continuous. Comparing sleep restriction versus control sleep, 24-hour mean BP was higher (adjusted mean difference, day 12: 2.1 mm Hg [95% CI, 0.6–3.6], corrected P =0.016), endothelial function was attenuated ( P <0.001), and plasma norepinephrine increased ( P =0.011). Despite increased deep sleep, BP was elevated while asleep during sleep restriction and recovery. Post hoc analysis revealed that 24-hour BP, wakefulness, and sleep BP increased during experimental and recovery phases of sleep restriction only in women, in whom 24-hour and sleep systolic BP increased by 8.0 (5.1–10.8) and 11.3 (5.9–16.7) mm Hg, respectively (both P <0.001). Shortened sleep causes persistent elevation in 24-hour and sleep-time BP. Pressor effects are evident despite closely controlled food intake and weight, suggesting that they are primarily driven by the shortened sleep duration. BP increases are especially striking and sustained in women, possibly suggesting lack of adaptation to sleep loss and thus greater vulnerability to its adverse cardiovascular effects.

Background The prevalence of excessive daytime sleepiness (EDS) in the general population is reported to be 9 to 28 percent. Various social and biological factors have been reported to contribute to the development of EDS, such as cardiovascular disease, metabolic disorders as well as socioeconomic status. Medically, EDS is associated with poorer prognosis in patients with sleep disorders. However, whether sleepiness is an independent negative prognostic indicator in patients without sleep apnea is poorly understood. Objective To evaluate the relationship between self‐reported excessive daytime sleepiness (assessed by Epworth Sleepiness Scale) and the risk of all‐cause mortality in patients without obstructive sleep apnea (OSA). Methods We performed a retrospective cohort study in a large registry of patients seen at the Mayo Clinic Center for Sleep Medicine between November 17 th , 2009 and April 15 th , 2017. All patients received a diagnostic polysomnography and had completed Epworth Sleepiness Scale (ESS). The primary outcome of all‐cause mortality risk was computed using the Kaplan‐Meier analysis and Cox‐proportional hazard model with age, sex, body mass index (BMI), baseline comorbidities and sleep measurements as confounders. Results A total of 2746 non‐OSA patients were identified. The overall median age (IQR) was computed as 53 (40, 63) with 45% of patients identifying as males. The median follow‐up time was approximately 2.3 years. In a univariate analysis, daytime sleepiness was associated with the female sex, younger age and higher BMI. No significant differences were observed in vascular related diseases between sleepy and non‐sleepy patients. EDS was not significantly associated with all‐cause mortality with an adjusted hazard ratio of 1.23 (95% CI 0.86, 1.76; p =0.257). In addition, there was no significant association of EDS and the risk of all‐cause mortality even after stratifying by sex, age and BMI in non‐OSA patients. Conclusion EDS is not associated with all‐cause mortality in non‐OSA patients. Further prospective studies are needed to confirm this finding. Support or Funding Information This research was supported by NIH HL65176 and NIH HL114024. Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. image Kaplan–Meier survival curve of 8 years all‐cause mortality of non‐OSA patients with and without excessive daytime sleepiness (EDS) at baseline. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .