Dream Enactment Behavior Research Articles

The diagnostic challenge of dream-enactment behaviors.

Citation:Gorantla S, Rodriguez CL. The diagnostic challenge of dream-enactment behavior. J Clin Sleep Med. 2020;16(11):1837–1838.

Association of heart rate variability with REM sleep without atonia in idiopathic REM sleep behavior disorder.

Idiopathic rapid eye movement sleep behavior disorder (iRBD), characterized by rapid eye movement sleep without atonia (RSWA) and dream-enactment behavior, has been suggested to be a predictor of α-synucleinopathies. Autonomic instability, represented by heart rate variability, is a common characteristic of both iRBD and α-synucleinopathies. Previous studies reported that RSWA was associated with autonomic dysfunction and was a possible predictor of phenoconversion. Therefore, we sought to compare heart rate variability between iRBD and control groups and explore the relationship between heart rate variability and RSWA in patients with iRBD. Nocturnal polysomnographic data on 47 patients (28 men, 19 women) diagnosed with iRBD based on video-polysomnography and 26 age-matched and sex-matched controls were reviewed. The first 5-minute epoch with a stable electrocardiogram lead II on video-polysomnography was selected from stage N2, wake, and rapid eye movement. For quantification of RSWA, tonic activity was analyzed from the submentalis electromyogram and phasic activity from the submentalis and bilateral anterior tibialis electromyogram channels. Compared to the control group, the iRBD group showed significant reductions in the standard deviation of the R-R intervals, the root mean square of successive R-R interval differences, and high-frequency values. Quantified tonic activity was inversely correlated with normalized low-frequency values and low-frequency/high-frequency ratios and positively correlated with normalized high-frequency values. This study implied decreased cardiac autonomic function in patients with iRBD, which showed parasympathetic predominance. Heart rate variability of the patients with iRBD in this study was associated with quantified tonic RSWA, which was previously reported to be a possible predictor of phenoconversion.

A patient with subjective cognitive decline and recurrent dream-enactment behaviours in a memory clinic: potential diagnostic utility of cardiac 123 I-metaiodobenzylguanidine scintigraphy.

A patient with subjective cognitive decline and recurrent dream-enactment behaviours in a memory clinic: potential diagnostic utility of cardiac 123 I-metaiodobenzylguanidine scintigraphy.

REM Sleep Behavior Disorder among Veterans with and without Post-Traumatic Stress Disorder.

ObjectiveAmong veterans, the prevalence of rapid eye movement sleep behavior disorder (RBD) is higher than among the general population, and some evidence suggests that this is related to post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether the frequency of RBD differs depending on the presence of PTSD or trauma. MethodsPatients who underwent nocturnal polysomnography (PSG) and sleep-related questionnaire surveys at the Veteran Health Service Medical Center were reviewed retrospectively. Based on patients with PTSD (n=20; 100% male; 67.9±8.5 years of age), we matched patients exposed to trauma without PTSD (n23; 100% male; age 64.0±13.4) and patients without trauma (n=21; 100% male; age 59.86±10.9). ResultsPTSD patients reported dream enactment behavior more than the trauma-exposed group without PTSD or the control group (p=0.006). After adjusting for age, there were more RBD patients in the PTSD group than in the trauma exposed group (p=0.049). ConclusionThe results showed that RBD occurred significantly more in veterans with PTSD than those exposed to trauma, which suggests that there may be a pathophysiological association between PTSD and RBD.

Associated factors of REM sleep without atonia in younger (\u2264 50\u2009years) hospitalized psychiatric patients

BackgroundIsolated REM sleep without atonia (RSWA) as a main polysomnograhic feature of REM sleep behaviour disorder (RBD) is thought to be a prodromal or subclinical state of the disease. RSWA/RBD occurence in psychiatric population is much more frequent than in general population but its associated factors are still not known.MethodsWe invited 88 psychiatry in-patients to undervent video-polysomnography. The visual scoring was focused on RSWA in submentales and flexores digitales superficiales muscles. This parametr was subsequently correlated mainly with age/gender, their medication and mental status.ResultsThe RWSA was mostly still in normal range despite the fact, that selected psychiatry patients (≤ 50 years) were taking several classes of psychoactive medication. 3,6% had convincingly RBD, although 35.7% reported rare lifetime occurence of dream-enacting behaviour and 62.8% sporadic nightmares. We found correlation between RSWA and SNRI medication class (p = 0.015), specifically venlafaxine (p = 0.029) as well as quetiapine (p = 0.030). Another significant associated factors were current anxiety (p < 0.001) and depressive symptoms (p = 0.05), but we found no relation between RSWA and given diagnosis.ConlucionsIsolated RSWA in younger psychiatry patients might be a result of multiple factors, including medication and current mental status but these factors are in most cases not sufficient to manifest RBD.

Differential Impact on Isolated REM Sleep without Atonia by Varying Antidepressant Therapies.

REM sleep without atonia (RSWA) is characterized by increased phasic or tonic muscle activity in electromyography channels during polysomnography and usually causes REM sleep behaviour disorder, but RSWA also exists within healthy populations without dream-enactment behaviour, especially in psychiatric populations receiving antidepressant therapies. Evidence for differential impact of antidepressants on RSWA, and whether RSWA persists or resolves following changes in antidepressant therapy, remains limited. We present a 56-year-old woman with depression undergoing 3 polysomnograms while receiving 3 different distinct antidepressants. Her first polysomnogram demonstrated elevated REM sleep without atonia while receiving a tricyclic antidepressant. Following a switch to fluoxetine, her second polysomnogram showed greater elevation of REM sleep without atonia After a subsequent therapeutic switch to buproprion, a third polysomnogram showed interval decrease in RSWA amounts, lower than the initial levels found during tricyclic antidepressant administration. A switch from fluoxetine to bupropion was associated with markedly reduced RSWA amounts. The polysomnography findings in this case suggest that the type of antidepressant treatment differentially impacts levels of RSWA. The potential importance and implication to practicing psychiatrists is that bupropion, with selective action on dopamine reuptake rather than serotoninergic or acetylcholinergic neurotransmission, may have lesser tendency toward increasing REM sleep muscle activity levels. Additional prospective studies comparing polysomnographic RSWA in psychiatric populations are needed. The authors have no financial support, off-label use, or conflict of interest to declare.

Dream enactment behavior: review for the clinician.

Dream enactment behavior commonly occurs on occasion in normal children and adults. Disruptive and frequent dream enactment behavior may come to the attention of the clinician either as the primary reason for consultation or as a prominent characteristic of a patient with other sleep disorders. Questioning patients with chronic neurologic and psychiatric disorders may also reveal previously unrecognized behavior. In the absence of sleep pathology, process of dream enactment likely begins with active, often emotionally charged dream content that may occasionally break through the normal REM sleep motor suppressive activity. Disrupted sleep resulting from many possible causes, such as circadian disruption, sleep apnea, or medications, may also disrupt at least temporarily the motor-suppressive activity in REM sleep, allowing dream enactment to occur. Finally, pathological neurological damage in the context of degenerative, autoimmune, and infectious neurological disorders may lead to chronic recurrent and severe dream enactment behavior. Evaluating the context, frequency, and severity of dream enactment behavior is guided first and foremost by a structured approach to the sleep history. Physical exam and selected testing support the clinical diagnosis. Understanding the context and the likely cause is essential to effective therapy.

Predicting phenoconversion in pure autonomic failure.

To determine predicting factors and frequency of phenoconversion from pure autonomic failure (PAF) into a synucleinopathy with motor or cognitive involvement of multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB). We performed a retrospective review of all patients with PAF from 2001 to 2011 evaluated at Mayo Clinic, Rochester. Clinical follow-up and patient telephone calls were used to assess for development of symptoms and diagnosis of MSA, PD, or DLB. Clinical and laboratory variables were extracted with factors predictive of evolution assessed using group comparison, odds ratio, and logistical regression. Among 275 patients with PAF at presentation, 67 (24%) phenoconverted to a synucleinopathy with motor or cognitive involvement; 34 met criteria for MSA, while 33 met criteria for PD or DLB. Age at onset was younger in MSA phenoconverters. Clinical features at presentation influenced phenoconversion: severe bladder symptoms were more common in MSA phenoconverters; subtle motor signs were more frequent in MSA and PD/DLB phenoconverters. MSA phenoconverters were more likely to have higher supine norepinephrine levels and preganglionic pattern of anhidrosis. Presentation variables predicting MSA phenoconversion included subtle motor signs, supine norepinephrine levels, severe bladder symptoms, and dream enactment behavior. Presentation variables predictive of PD/DLB phenoconversion included subtle motor signs, dream enactment behavior, and constipation. Our findings suggest that at least a quarter of patients with PAF phenoconvert to MSA, PD, or DLB. Presentation features determine patients at risk for evolution with specific patterns indicative of phenoconversion to MSA vs PD/DLB. This study provides Class II evidence that several presentation variables including subtle motor signs, severe bladder symptoms, and dream enactment behavior are associated with an increased risk of developing a synucleinopathy with motor or cognitive involvement.

0800 Posttraumatic Stress Disorder and REM Sleep Without Atonia in Veterans

Abstract Introduction In veterans, the prevalence of rapid eye movement (REM) sleep behavior disorder(RBD) is higher than the general population, and there is some evidence that this is related to posttraumatic stress disorder(PTSD). In addition, trauma related nightmares (TRNs) interfere with REM sleep and are often accompanied by motor activity. (rem sleep without atonia; RSWA). The purpose of this study is to determine whether the frequency of dream enactment behavior(DEB) and RSWA is different according to the presence of PTSD or trauma. Methods The patients (n = 2262) who underwent video assisted polysomnography (PSG) and sleep-related questionnaire surveys at Veteran Health Service Medical Center in Republic of Korea were reviewed retrospectively and cross-sectionally. Based on patients diagnosed with PTSD (N = 20; 100% male; 67.9 ± 8.5 years of age), those exposed to trauma but not diagnosed with PTSD (N = 23; 100% male; age 64.0 ± 13.4) and trauma unexposed controls (N = 21; 100% male; age 59.86 ± 10.9) were matched. Results In the PTSD group, patients who reported self-reported DEB tended to be more than the traumatic exposure group and the control group (P = 0.022). In-lab video assisted PSG showed no differences in DEB between the three groups, but RSWA. (p = 0.026) After adjusting for age, hypnotics, apnea hypopnea index (AHI), Beck depression inventory (BDI), and periodic limb movement (PLM) arousal factors, RSWA was significantly higher in the PTSD group than in the traumatic exposure group. (p = 0.006) Conclusion The result that RSWA was significantly higher in the PTSD group than in the traumatic exposure group suggests that there may be an associated pathophysiology between PTSD and RBD. Longitudinal studies are needed to establish the link between RBD with PTSD and neurodegenerative diseases associated with synucleinopathy. Support This study was supported by a VHS Medical Center Research Grant, Republic of Korea. (grant number: VHSMC 19033)

0003 LGI1 and CASPR2 Autoimmunity: Sleep Symptoms, Polysomnography, and Quantitative REM Sleep without Atonia

Abstract Introduction Sleep disturbances, including rapid eye movement (REM) behavior disorder (RBD), are known manifestations of voltage-gated-potassium-channel-complex VGKC-IgG seropositivity (VGKC+). Discovery of leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) have refined our understanding of VGKC+. VGKC+ without LGI1/CASPR2-IgG (“double-negative”) has lost its clinical significance. Previous detailed sleep analysis of these subtypes has been limited. Methods We performed a retrospective study to characterize clinical and polysomnographic features of LGI1/CASPR2 seropositive (LGI1+/CASPR2+) and VGKC double-negative patients, including quantitative REM sleep without atonia (RSWA). Quantified RSWA was compared to matched controls and normative RSWA percentiles. Results Eleven LGI1+/CASPR2+ (LGI1+, 9) and twelve VGKC double-negative patients were analyzed. Insomnia was seen in 55% of LGI1+/CASPR2+ and 8% of VGKC double-negative patients (p=0.05). The LGI1+/CASPR2+ group had reduced slow wave sleep compared to the VGKC double-negative group. Five LGI1+ patients had clinical dream enactment behavior (DEB). Eight LGI1+ patients met quantitative diagnostic levels of RSWA. Higher RSWA levels were seen in the LGI1+/CASPR2+ group. Ten LGI1+/CASPR2+ patients received immunotherapy; all ten neurologically benefited with sleep benefits in 6/10. Conclusion Sleep disorders such as insomnia and RBD are part of the LGI1/CASPR2 autoimmune phenotype. Objective sleep manifestations can be seen on polysomnogram in the form of reduced N3 and elevated RSWA as compared to controls. Quantitative RSWA analysis identified RBD in more LGI1+ patients than clinical report or qualitative RSWA. In this study, RBD was only seen with LGI1+, not CASPR2+. The intermediate RSWA levels of the VGKC double-negative patients may suggest a spectrum of abnormal motor activity in these related antibodies. Additional studies are needed to further explore the biomarker potential of quantitative RSWA in autoimmune neurological conditions. Support This project was supported by the National Center forResearch Resources, National Institutes of Health, through Grant Number 1 UL1 RR024150- 01.

1230 An unusual presentation of dementia with Lewy bodies in a septuagenarian

Abstract Introduction Dementia with Lewy bodies (DLB) can be associated with degeneration of the hypocretin system and reduced hypocretin levels. However, reports of DLB initially presenting with narcolepsy with cataplexy symptoms are sparse. Report of Case A 77-year-old man presents with two years of new onset hypersomnia, tremors, memory difficulties, and gait instability. Before his sleep evaluation, he was started on levetiracetam for suspected seizures and levodopa for suspected Parkinson’s disease, without improvement. During his evaluation for hypersomnia, he reported loud snoring, witnessed apneas, sleep maintenance difficulty, hypnagogic hallucinations of well-formed images, and vivid dreams with dream enactment behavior occurring almost nightly. He had witnessed episodes of cataplexy described as transient lower extremity weakness with associated bifacial weakness, inability to speak, and no loss of consciousness, self-injury, loss of bowel/bladder control, or post-event symptoms. These events completely resolved after 1-minute, occurred while sitting or standing, and were spontaneous or triggered by anger or anxiety. His Epworth Sleepiness Scale was 18 and Ullanlinna Narcolepsy Scale was 35, suggestive of narcolepsy with cataplexy. Physical examination did not reveal Parkinsonism or resting tremor. He subsequently underwent a baseline polysomnogram that showed an apnea-hypopnea index of 32.7 events/hour. During an in-laboratory titration study, he had REM sleep without atonia. A 30-minute EEG was interpreted as normal and a typical cataplexy-like event captured during continuous EEG monitoring had no ictal correlate. Despite adherence to positive airway pressure therapy, he continued to have hypersomnia, cataplexy, and visual hallucinations during transitions from wake to sleep. He was tapered off levetiracetam and levodopa with a plan for further evaluation of probable DLB. Conclusion Narcolepsy with cataplexy symptoms is an uncommon presentation of probable DLB as seen in this case with two core clinical features of DLB (RBD and visual hallucinations), suggesting neurodegeneration of the hypocretin system.

0418 Effect of Acute Administration of DORA-12 on Sleep Impairment in the Aged PS19 Mouse Model of Tauopathy

Abstract Introduction Aged PS19 mice (MAPT P301S), a mouse model of tauopathy and neurodegeneration, display reduced NREM and REM sleep starting around 8-9 months before death around 12 months. Here, we tested the acute effect of a dual orexin receptor antagonist (DORA-12) on sleep in 11 mice (5 male, 6 female) at 10.3±1.8 months. Methods Two consecutive 24-hour recordings (12/12hr L:D cycle) were scored semi-automatically for non-REM sleep, REM sleep, and wake in mice implanted with EEG/EMG. Mice were treated with either vehicle (day 1) or 100mg/kg of DORA-12 (day 2) by oral gavage at both ZT0 and ZT9. Results After the first dose at ZT0, both latency to the first NREM sleep episode (paired t-test p=0.002) and to the first REM sleep episode (paired t-test p=0.005) was significantly shorter with DORA-12 (NREM: 20.8±17.8 min.; REM: 23.5±21.2 min.) compared to vehicle (NREM: 49.2±22.3 min.; REM: 127.0±93.3 min.). There was no difference in NREM or REM sleep latency observed after the second dose at ZT9. DORA-12 treatment increased NREM duration across the 24hr period (DORA-12: 664±52 min.; Veh: 601±54 min., paired t-test p=0.007) and also after the 2nd dose (DORA-12: 311±65 min.; Veh: 263±84 min., paired t-test p=0.009). DORA-12 treatment also increased REM duration across 24hrs (DORA-12: 61±30 min.; Veh: 48±29 min., paired t-test p=0.014) but not after the 2nd dose alone (DORA-12: 22±14 min.; Veh: 20±15 min., paired t-test p=0.388). Notably in both vehicle and DORA-12 conditions, we observed apparent dream enactment behavior including mastication, paw grasp, and fore limb extension during REM in 3 of 11 PS19 mice (all male), not typically observed in younger PS19 or age-matched non-transgenic mice, suggestive of a possible REM behavior disorder (RBD) phenotype. Wake-like behaviors occurred during theta-dominant EEG but with an EMG amplitude &amp;gt;4SD the preceding NREM sleep baseline for at least &amp;gt; 1sec. Conclusion In aged PS19 mice, DORA-12 was found to decrease the latency to NREM and REM after the first dose while also increasing NREM and REM duration across the entire 24hr recording period. We also capture a heretofore undescribed RBD-like phenotype in aged PS19 tauopathy mice. Support Merck MISP

Self-Reported Rapid Eye Movement Sleep Behavior Disturbance and Its Associated Factors among Medicine and Health Science Students at the University of Gondar.

Introduction Rapid eye movement sleep behavior disorder (RBD) is characterized by dream-enacting behavior (shouting, punching, and falling out of bed) related to unpleasant dreams and loss of normal rapid eye movement (REM) sleep muscle atonia. Rapid eye movement sleep enhances learning and memory by regulating neuronal synapses, and if it is undesirable, it can lead to cognitive impairment and poor academic performance and may end up with death. To the best of our searching databases, there is no such study conducted in Ethiopia. Therefore, this study is aimed at determining self-reported symptoms of RBD and its associated factors among the University of Gondar medicine and health science students (2019). Methods We conducted a cross-sectional study from June 1 to July 2019, among medicine and health science students at the University of Gondar using a simple random sampling technique. A self-reported RBD screening questionnaire was used to collect the data. We used Epi Info™ 7.0.8.3 and Stata 14 for data entry and statistical analyses, respectively. Descriptive statistics (frequency with percent and mean with standard deviation) and adjusted odds ratio (AOR) with 95% uncertainty interval (UI) were computed. In a multivariable binary logistic regression, variables with a p < 0.05 were declared as significant. Results Three hundred and eighty-seven students took part in the study. The mean age of participants was 20.81 (±1.83) years. The prevalence of self-reported RBD was 46.25% [95% UI (41.26%-51.24)]. Physical exercise immediately before sleep (AOR = 2.50, 95% UI (1.24-5.02)), using Facebook immediately before sleep (AOR = 1.93, 95% UI (1.18-3.15)), having daytime sleepiness (AOR = 1.92, 95% UI (1.16-3.19)), and self-reported depressive symptoms (AOR = 2.40, 95% UI (1.45-3.99)) were significantly associated with self-reported RBD. Conclusion The current study revealed a high prevalence of self-reported RBD. This remarkable problem suggested a need to design strategies to prevent RBD symptoms among university students through targeting screening of depression, daytime sleepiness, and adjusting bedtime routines such as physical exercise and internet use immediately before going to bed.

Prevalence and predictors of mood disturbances in idiopathic REM sleep behaviour disorder.

Depression and anxiety are commonly associated with synucleinopathies. Mood disturbances have also been reported in patients with idiopathic REM sleep behaviour disorder (iRBD) and are difficult to treat due to exacerbation of sleep symptoms with standard antidepressants. Despite this, detailed prevalence studies of mood symptomatology and contributors to mood disturbances in iRBD are limited. Mood, sleep, autonomic, cognitive and motor symptoms were assessed in 49 well-characterized patients with iRBD using a variety of clinical scales. Spearman correlations, factor analysis and multiple linear regression were used to uncover associations between mood and non-motor and motor symptoms. The prevalence of significant depression was 17.0% and that of anxiety was 14.6% in the iRBD cohort. Age and disease duration were not correlated with these affective symptoms in iRBD patients. We found depression was significantly predicted by the presence and severity of motor, sleep and cognitive symptoms. Anxiety was predicted by the severity of nocturnal and daytime sleep-related symptoms, cognitive symptoms and autonomic symptoms, with a differential effect depending on the questionnaire used. Depression and anxiety are common in iRBD patients and can be significantly explained by specific sets of non-motor and motor symptoms. These associations provide insight into the underlying pathophysiology and emphasize the importance of a holistic approach to mood disturbance in this population, which may circumvent the reliance on pharmacotherapy that can exacerbate dream enactment behaviour.

Diagnosing REM sleep behavior disorder in Parkinson's disease without a gold standard: a latent-class model study.

To ascertain whether current diagnostic criteria for REM sleep behavior disorder (RBD) are appropriate in patients with Parkinson's disease (PD) consulting a movement disorder center, to evaluate the accuracy of REM sleep without atonia (RSWA) thresholds and determine the value of screening questionnaires to discriminate PD patients with RBD. One hundred twenty-eight consecutive PD patients (M = 80; mean age: 65.6 ± 8.3 years) underwent screening questionnaires, followed by a sleep-focused interview and a full-night video-polysomnography (vPSG). Without a gold standard, latent class models (LCMs) were applied to create an unobserved ("latent") variable. Sensitivity analysis was performed using RSWA cutoff derived from two visual scoring methods. Finally, we assessed the respective diagnostic performance of each diagnostic criterion for RBD and of the screening questionnaires. According to the best LCM-derived model, patients having either "history" or "video" with RSWA or alternatively showing both "history" and "video" without RSWA were classified as having RBD. Using both SINBAR and Montreal scoring methods, RSWA criterion showed the highest sensitivity while concomitant history of RBD and vPSG-documented behaviors, regardless to presence of RSWA, displayed the highest specificity. Currently recommended diagnostic threshold of RSWA was found to be optimal in our large cohort of PD patients. Both the RBD screening questionnaire (RBDSQ) and the RBD single question (RBD1Q) showed poor sensitivity and specificity. Results of the best LCM for diagnosis of RBD in PD were consistent with the current diagnostic criteria. Moreover, RBD might be considered in those PD patients with both history and vPSG-documented dream enactment behaviors, but with RSWA values within the normal range.

Prevalence and clinical characteristics of REM sleep behavior disorder in Japanese elderly people.

To evaluate the prevalence and clinical characteristics of isolated REM sleep behavior disorder (iRBD) among a general population of elderly Japanese people. This epidemiological study targeted 2714 elderly residents (76.0 ± 8.0 years, 52.9% female) of a rural community. Questionnaires including the REM sleep behavior disorder single question and demographic information were distributed. All respondents with the question positive were interviewed by telephone. Respondents suspected of having iRBD proceeded to face-to-face interviews and underwent video-polysomnography and neurological/neuropsychological examination. These results were compared to those of previously diagnosed clinical iRBD patients in our sleep clinic. Of 1464 respondents to the questionnaire, 18 respondents were diagnosed as iRBD (1.23 [0.66-1.79]%), including eight respondents who satisfied diagnostic criteria with REM sleep without atonia (RWA) above the cut-off value (0.54 [0.17-0.92]%) and 10 respondents who had clear dream enactment behaviors but not RWA above the cut-off (provisionally diagnosed iRBD; p-iRBD) (0.69 [0.26-1.11]%). Severity of RBD and RWA of the population-based iRBD were compatible with those of the clinical iRBD. Half of the population-based iRBD showed orthostatic hypotension and they showed lower olfactory function than population-based p-iRBD and non-RBD. However, their olfactory and cognitive functions were higher than those in the clinical iRBD patients. Prevalence of iRBD in Japanese elderly people was comparable with the rate reported from other countries. Population-based iRBD/p-iRBD showed lower neurodegenerative loading than clinical iRBD in spite of comparable disease duration of RBD, that may indicate their lower risk of future neurodegeneration.

Contrast sensitivity visual acuity in REM sleep behavior disorder: a comparison with and without Parkinson disease.

REM sleep behavior disorder (RBD) is characterized by dream enactment behavior and is a premotoric sign associated with parkinsonism and dementia. We previously found contrast sensitivity visual acuity (CSVA) deficiencies in earliest stages of Parkinson disease (PD), plausibly associated with alpha-synuclein deposits in the inner retinal layers. We speculated that individuals with REM sleep behavior without clinical signs of parkinsonism might also show similar deficiencies. Twenty-three patients with RBD and 28 healthy control patients. Eleven with PD and 12 with idiopathic RBD (iRBD). Twelve patients with RBD were re-evaluated after 1 year. Evaluations consisted of CSVA SLOAN low contrast acuity charts, optical coherence topography, Unified Parkinson's Disease Rating Scale (UPDRS), and general neurologic and ophthalmologic examinations. Data analyzed between groups using a one-way analysis of variance, and a paired samples t test for returning patients. Participants were classified into three groups: controls (n = 28), iRBD (n = 12), and RBD+PD (n = 11). Analysis of variance revealed CSVA scores were statistically significantly different between the three groups F2, 50 = 7.037, P = .002. Longitudinal analysis of RBD group showed CSVA decreased significantly at 1 year (P = .0141). To date, PD has developed in three individuals with iRBD based on progression of their UPDRS scores. CSVA is reduced in individuals with RBD and declines over time. It is plausible that patients with iRBD may show early loss in dopaminergic lateral inhibition in the retina, evidenced by their progressive loss of CSVA. This may represent a global loss of dopaminergic neurons similar to PD.

Comorbid Depression Is Associated with a Negative Treatment Response in Idiopathic REM Sleep Behavior Disorder

Background and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD).MethodsWe reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment.ResultsForty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029).ConclusionsWe found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.

REM sleep atonia loss distinguishes synucleinopathy in older adults with cognitive impairment.

To determine whether quantitative polysomnographic REM sleep without atonia (RSWA) distinguishes between cognitive impairment phenotypes. Neurodegenerative cognitive impairment in older adults predominantly correlates with tauopathy or synucleinopathy. Accurate antemortem phenotypic diagnosis has important prognostic and treatment implications; additional clinical tools might distinguish between dementia syndromes. We quantitatively analyzed RSWA in 61 older adults who underwent polysomnography including 46 with cognitive impairment (20 probable synucleinopathy), 26 probable non-synucleinopathy (15 probable Alzheimer disease, 11 frontotemporal lobar dementia), and 15 age- and sex-matched controls. Submentalis and anterior tibialis RSWA metrics and automated REM atonia index were calculated. Group statistical comparisons and regression were performed, and receiver operating characteristic curves determined diagnostic RSWA thresholds that best distinguished synucleinopathy phenotype. Submentalis-but not anterior tibialis RSWA-was greater in synucleinopathy than nonsynucleinopathy; several RSWA diagnostic thresholds distinguished synucleinopathy with excellent specificity including submentalis tonic, 5.6% (area under the curve [AUC] 0.791); submentalis any, 15.0% (AUC 0.871); submentalis phasic, 10.8% (AUC 0.863); and anterior tibialis phasic, 31.4% (AUC 0.694). In the subset of patients without dream enactment behaviors, submentalis RSWA was also greater in patients with synucleinopathy than in those without synucleinopathy. RSWA was detected more frequently by quantitative than qualitative methods (p = 0.0001). Elevated submentalis RSWA distinguishes probable synucleinopathy from probable nonsynucleinopathy in cognitively impaired older adults, even in the absence of clinical dream enactment symptoms. This study provides Class III evidence that quantitative RSWA analysis is useful for distinguishing cognitive impairment phenotypes. Further studies with pathologic confirmation of dementia diagnoses are needed to confirm the diagnostic utility of RSWA in dementia.

Migraine aura, a predictor of near-death experiences in a crowdsourced study.

BackgroundNear-death experiences (NDE) occur with imminent death and in situations of stress and danger but are poorly understood. Evidence suggests that NDE are associated with rapid eye movement (REM) sleep intrusion, a feature of narcolepsy. Previous studies further found REM abnormalities and an increased frequency of dream-enacting behavior in migraine patients, as well as an association between migraine with aura and narcolepsy. We therefore investigated if NDE are more common in people with migraine aura.MethodsWe recruited 1,037 laypeople from 35 countries and five continents, without any filters except for English language and age ≥18 years, via a crowdsourcing platform. Reports were validated using the Greyson NDE Scale.ResultsEighty-one of 1,037 participants had NDE (7.8%; CI [6.3–9.7%]). There were no significant associations between NDE and age (p > 0.6, t-test independent samples) or gender (p > 0.9, Chi-square test). The only significant association was between NDE and migraine aura: 48 (6.1%) of 783 subjects without migraine aura and 33 (13.0%) of 254 subjects with migraine aura had NDE (p < 0.001, odds ratio (OR) = 2.29). In multiple logistic regression analysis, migraine aura remained significant after adjustment for age (p < 0.001, OR = 2.31), gender (p < 0.001, OR = 2.33), or both (p < 0.001, OR = 2.33).ConclusionsIn our sample, migraine aura was a predictor of NDE. This indirectly supports the association between NDE and REM intrusion and might have implications for the understanding of NDE, because a variant of spreading depolarization (SD), terminal SD, occurs in humans at the end of life, while a short-lasting variant of SD is considered the pathophysiological correlate of migraine aura.