Automatic video analysis and classification of sleep-related hypermotor seizures and disorders of arousal.

OBJECTIVE: Sleep-related hypermotor epilepsy (SHE) is a focal epilepsy with seizures occurring mostly during sleep. SHE seizures present different motor characteristics ranging from dystonic posturing to hyperkinetic motor patterns, sometimes associated with affective symptoms and complex behaviors. Disorders of arousal (DOA) are sleep disorders with paroxysmal episodes that may present analogies with SHE seizures. Accurate interpretation of the different SHE patterns and their differentiation from DOA manifestations can be difficult and expensive, and can require highly skilled personnel not always available. Furthermore, it is operator dependent. METHODS: Common techniques for human motion analysis, such as wearable sensors (e.g., accelerometers) and motion capture systems, have been considered to overcome these problems. Unfortunately, these systems are cumbersome and they require trained personnel for marker and sensor positioning, limiting their use in the epilepsy domain. To overcome these problems, recently significant effort has been spent in studying automatic methods based on video analysis for the characterization of human motion. Systems based on computer vision and deep learning have been exploited in many fields, but epilepsy has received limited attention. RESULTS: In this paper, we present a pipeline composed of a set of three-dimensional convolutional neural networks that, starting from video recordings, reached an overall accuracy of 80% in the classification of different SHE semiology patterns and DOA. SIGNIFICANCE: The preliminary results obtained in this study highlight that our deep learning pipeline could be used by physicians as a tool to support them in the differential diagnosis of the different patterns of SHE and DOA, and encourage further investigation.

Psychobiological personality traits of children and adolescents with disorders of arousal.

INTRODUCTION: Disorders of arousal (DOA) are parasomnias that emerge from incomplete arousal out of Non-Rem Sleep (NREM) and lead to a broad variety of emotional and motor behaviours. Increasing evidence supports the hypothesis that specific psychopathological traits contribute to the multifactorial origin of these phenomena. The aim of the current multicenter study was to compare the personality profile of children and adolescents with and without DOA using the Junior Temperament and Character Inventory (JTCI). METHODS: We enrolled 36 patients with a diagnosis of DOA (mean age of 11 ± 3 years, 64% males), and 36 healthy age and gender matched control subjects (mean age of 11.2 ± 3.6, years, 67% males). Their parents completed the Paris Arousal Disorder Severity Scale (PADSS), the Sleep Disturbance Scale for Children (SDSC) and the JTCI. RESULTS: Patients with DOA reached significantly higher levels compared to their control group in total PADSS (p < 0.0001) and in total SDSC (p < 0.0001). They also displayed higher scores in novelty seeking (p = 0.005), harm avoidance (p = 0.01), self-transcendence (p = 0.006) JTCI subscales, and lower scores on the self-directedness subscale (p = 0.004). CONCLUSION: Our pediatric sample with DOA exhibited specific psychobiological personality traits compared to age and gender matched subjects without DOA. These results shed light on new possible etiopathogenetic mechanisms, as TCI traits have been linked to specific genetic variants and brain circuits, like the reward system. Prospective studies are required to assess the effect of targeted psychological/psychiatric treatment on DOA symptomatology.

Drugs Used in Parasomnia.

Parasomnias, especially disorders of arousal during childhood, are often relatively benign and transitory and do not usually require a pharmacologic therapy. A relevant aspect in both nonrapid eye movement and rapid eye movement parasomnia treatment is to prevent sleep-related injuries by maintaining a safe environment. Physicians should always evaluate the possible presence of favoring and precipitating factors (sleep disorders and drugs). A pharmacologic treatment may be indicated in case of frequent, troublesome, or particularly dangerous events. The aim of this article is to review current available evidence on pharmacologic treatment of different forms of parasomnia.

Insomnia in primary care: a survey conducted on Italian patients older than 50 years-results from the "Sonno e Salute" study.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p < 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p < 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p < 0.001), z-drugs (p = 0.012), antidepressants (p < 0.001), and melatonin-prolonged release (p < 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort.

INTRODUCTION: Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naïve patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). METHODS: We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. RESULTS: One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. CONCLUSION: Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach.

Sleep and epilepsy: A snapshot of knowledge and future research lines.

Sleep and epilepsy have a reciprocal relationship, and have been recognized as bedfellows since antiquity. However, research on this topic has made a big step forward only in recent years. In this narrative review we summarize the most stimulating discoveries and insights reached by the "European school." In particular, different aspects concerning the sleep-epilepsy interactions are analysed: (a) the effects of sleep on epilepsy; (b) the effects of epilepsy on sleep structure; (c) the relationship between epilepsy, sleep and epileptogenesis; (d) the impact of epileptic activity during sleep on cognition; (e) the relationship between epilepsy and the circadian rhythm; (f) the history and features of sleep hypermotor epilepsy and its differential diagnosis; (g) the relationship between epilepsy and sleep disorders.

Predictors of hyperkinetic seizures.

OBJECTIVE: To identify predisposing factors for hyperkinetic seizure occurrence in a representative cohort of surgically treated patients with drug-resistant focal epilepsy. METHODS: We retrospectively recruited all seizure-free patients after epilepsy surgery with a postoperative follow-up ≥12 months. Patients were classified as presenting with hyperkinetic seizures if at least 2 episodes occurred during their disease history, based on clear-cut anamnestic description and/or video-EEG/stereo-EEG recordings. We performed univariable and multivariable logistic regression models to study the association between the occurrence of hyperkinetic seizures and some predictors. RESULTS: From a pool of 1758 consecutive patients who underwent surgery from 1996 to 2017, we identified 974 seizure-free cases. Considering at least 1-year follow-up, 937 cases were included (511 males, 91 patients with hyperkinetic seizures). Variables significantly associated with an increased risk of hyperkinetic seizure occurrence were (1) presence of epilepsy with sleep-related seizures (SRE) (P < 0.001); (2) histological diagnosis of type II focal cortical dysplasia (FCD) (P < 0.001); (3) resection including the frontal lobe (P = 0.002) (4) duration of epilepsy at surgery (P < 0.001) and (5) high seizure frequency at surgery (weekly: P = 0.02 - daily: P = 0.05). A resection including the occipital lobe reduced the risk of hyperkinetic seizures (P = 0.05). About 63% of patients had hyperkinetic seizure onset before 12 years and it was rarely reported before 5 years of age. SIGNIFICANCE: Our findings underlie the role of SRE, type II FCD and frontal epileptogenic zone as predictors of hyperkinetic seizure occurrence and highlight an age-dependent effect in favoring hyperkinetic manifestations.

Sleep disorders and mental health in hospital workers during the COVID-19 pandemic: a cross-sectional multicenter study in Northern Italy.

INTRODUCTION: From the beginning of the COVID-19 pandemic, healthcare workers had to face unprecedented emergency needs associated with an extraordinary amount of psychological distress. In this cross-sectional multicenter study, we investigated sleep disturbances, and the level of anxiety and depression among the healthcare and non-healthcare staff of three hospitals in Milan (Italy) during the COVID-19 outbreak. Moreover, we explored potential predisposing factors for affective symptoms and poor sleep. METHODS: Between June and July 2020, we administered an online questionnaire to evaluate the presence of sleep disorders (Pittsburgh Sleep Quality Index), insomnia (Sleep Condition Indicator), anxiety (State Trait Anxiety Inventory), and depression (Beck Depression Inventory-II). We used univariate and multivariate analysis to evaluate the association between the personal conditions and sleep and affective disorders. RESULTS: The 964 participants reported high rates of sleep disorders (80.3%)-mainly insomnia (30.5%)-anxiety (69.7%), and depression (32.8%). The multivariate analysis showed a strong association of sleep disorders, especially insomnia, with female gender (p = 0.004), divorced marital status (p = 0.015), self-isolation (p = 0.037), and chronic diseases (p = 0.003). Anxiety was significantly associated with teleworking (p = 0.001), while depressive symptoms were associated with self-isolation (p = 0.028), modified work schedules (p = 0.03), and chronic diseases (p = 0.027). CONCLUSION: In hospital workers, the high prevalence of sleep and psychiatric symptoms during the COVID-19 outbreak appears to be determined mainly by modifications of personal or work habits. Teleworking was associated with increased anxiety. An accurate planning of hospital activities and a psychological support are needed to prevent and manage sleep and mental disorders.

The actigraphic documentation of circadian sleep-wake rhythm dysregulation in myotonic dystrophy type 1.

STUDY OBJECTIVES: The present study aimed at identifying the sleep-wake rhythm in patients with myotonic dystrophy type 1 (DM1) compared to healthy controls. METHODS: Patients with genetic diagnosis of DM1 and healthy controls underwent a 7-day actigraphic recording and filled out a daily sleep diary to evaluate the sleep-wake rhythm. All participants underwent a physical and neurological examination to exclude conditions interfering with the sleep-wake cycle. Daytime activity, nocturnal sleep, and non-parametric circadian rhythm activity (NPCRA) were analysed. RESULTS: Twenty-nine patients affected by DM1 were included in the present study and were compared to 16 controls. Considering nocturnal actigraphic data, DM1 patients showed a longer time in bed, sleep period time, actual sleep time, and sleep latency compared to controls. Central phase measurement was significantly longer in DM1 patients than controls. At NPCRA analysis patients showed a lower degree of regularity in the activity-rest pattern compared to controls. Moreover, DM1 patients showed reduced motor activity during daytime and a lower synchronization of the rest-activity rhythm than controls. CONCLUSIONS: This study documented that patients with DM1 not only present the impairment of nocturnal sleep, but also show a dysregulation of the sleep-wake circadian rhythm; moreover, reduced amplitude of the circadian rhythmicity was also evident in comparison to controls, probably in relation to the reduced diurnal motor activity of patients. These findings add further evidence to the already documented sleep impairment and excessive daytime sleepiness in DM1 patients.

Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 is mostly of central origin but it may coexist with sleep-related breathing disorders. However, there is no consensus on the sleep protocols to be used, assessments vary, and only a minority of patients are regularly tested or are on treatment for EDS. Our study presents data on self-reported and objective EDS in adult-onset myotonic dystrophy type 1. METHODS: Sixty-three patients with adult-onset DM1 were subjected to EDS-sleep assessments (polysomnography, Multiple Sleep Latency Test, Epworth Sleepiness Scale). Correlation coefficients were computed to assess the relationship between sleep and sleepiness test results, fatigue, and quality of life. RESULTS: 33% and 48% of patients had EDS based, respectively, on the Epworth Sleepiness Scale and the Multiple Sleep Latency Test, with a low concordance between these tests (k = 0.19). Thirteen patients (20%) displayed 2 or more sleep-onset rapid eye movement periods on Multiple Sleep Latency Test. Patients having EDS by Multiple Sleep Latency Test had a shorter disease duration (P < .05), higher total sleep time and sleep efficiency and lower wake after sleep onset on polysomnography. Patients with self-reported EDS reported significantly higher fatigue score compared with patients without EDS (P < .05). No other difference was found in demographic, clinical, and respiratory features. CONCLUSIONS: EDS test results are contradictory, making treatment options difficult. Combining quantitative tests and self-reported scales may facilitate physicians in planning EDS care with patients and families. CITATION: Sansone VA, Proserpio P, Mauro L, et al. Assessment of self-reported and objective daytime sleepiness in adult-onset myotonic dystrophy type 1. J Clin Sleep Med. 2021;17(12):2383-2391.

Behavioural and emotional profiles of children and adolescents with disorders of arousal.

Disorders of arousals are common sleep disorders characterized by complex motor behaviours that arise episodically out of slow-wave sleep. Psychological distress has long been associated with disorders of arousal, but this link remains controversial, especially in children and adolescents. The aim of this multi-centre study was to characterize behavioural and emotional problems in a sample of children/adolescents with disorders of arousal, and to explore their relationship with the severity of nocturnal episodes. The parents of 41 children/adolescents with a diagnosis of disorders of arousal (11.5 ± 3.3 years old, 61% males) and of a group of 41 age- and gender-matched control participants filled in the Child Behavior Checklist, along with the Sleep Disturbance Scale for Children and the Paris Arousal Disorders Severity Scale. Multilevel t-tests revealed significantly higher total scores and sub-scores of the Child Behavior Checklist for the patient group compared with the control group. Thirty-four percent of the patients obtained pathological total scores, and 12% of them borderline scores. The severity of emotional/behavioural problems in the patient group was positively correlated with the severity of the nocturnal episodes. Interestingly, children/adolescents with disorders of arousal also obtained higher excessive daytime sleepiness and insomnia symptoms sub-scores at the Sleep Disturbance Scale for Children. These results confirmed the hypothesis that behavioural/emotional problems are surprisingly common in children/adolescents with disorders of arousal. Further studies are warranted to investigate the causal relationship between pathological manifestations, subtler sleep abnormalities, and diurnal emotional/behavioural problems in children/adolescents with disorders of arousal.

Drugs Used in Parasomnia.

Patient education and behavioral management represent the first treatment approaches to the patient with parasomnia, especially in case of disorders of arousal (DOA). A pharmacologic treatment of DOA may be useful when episodes are frequent and persist despite resolution of predisposing factors, are associated with a high risk of injury, or cause significant impairment, such as excessive sleepiness. Approved drugs for DOA are still lacking. The most commonly used medications are benzodiazepines and antidepressants. The pharmacologic treatment of rapid eye movement sleep behavior disorder is symptomatic, and the most commonly used drugs are clonazepam and melatonin.

Cardiac autonomic dynamics during sleep are lost in patients with TIA and stroke.

Ischaemic stroke is accompanied by important alterations of cardiac autonomic control, which have an impact on stroke outcome. In sleep, cardiac autonomic control oscillates with a predominant sympathetic modulation during REM sleep. We aimed to assess cardiac autonomic control in different sleep stages in patients with ischaemic stroke. Forty-five patients enrolled in the prospective, multicentre SAS-CARE study but without significant sleep-disordered breathing (apnea-hypopnea index < 15/hr) and without atrial fibrillation were included in this analysis. The mean age was 56 years, 68% were male, 76% had a stroke (n = 34, mean National Institutes of Health Stroke Scale [NIHSS] score of 5, 11 involving the insula) and 24% (n = 11) had a transitory ischaemic attack. Cardiac autonomic control was evaluated using three different tools (spectral, symbolic and entropy analysis) according to sleep stages on short segments of 250 beats in all patients. Polysomnographic studies were performed within 7 days and 3 months after the ischaemic event. No significant differences in cardiac autonomic control between sleep stages were observed in the acute phase and after 3 months. Predominant vagal modulation and decreased sympathetic modulation were observed across all sleep stages in ischaemic stroke involving the insula. Patients with ischaemic stroke and transitory ischaemic attack present a loss of cardiac autonomic dynamics during sleep in the first 3 months after the ischaemic event. This change could represent an adaptive phenomenon, protecting the cardiovascular system from the instabilities of autonomic control, or a risk factor for stroke, which precedes the ischaemic event.

Polysomnographic features differentiating disorder of arousals from sleep-related hypermotor epilepsy.

OBJECTIVE: The differential diagnosis between sleep-related hypermotor epilepsy (SHE) and disorders of arousal (DOA) may be challenging. We analyzed the stage and the relative time of occurrence of parasomnic and epileptic events to test their potential diagnostic accuracy as criteria to discriminate SHE from DOA. METHODS: Video-polysomnography recordings of 89 patients with a definite diagnosis of DOA (59) or SHE (30) were reviewed to define major or minor events and to analyze their stage and relative time of occurrence. The "event distribution index" was defined on the basis of the occurrence of events during the first versus the second part of sleep period time. A group analysis was performed between DOA and SHE patients to identify candidate predictors and to quantify their discriminative performance. RESULTS: The total number of motor events (i.e. major and minor) was significantly lower in DOA (3.2 ± 2.4) than in SHE patients (6.9 ± 8.3; p = 0.03). Episodes occurred mostly during N3 and N2 in DOA and SHE patients, respectively. The occurrence of at least one major event outside N3 was highly suggestive for SHE (p = 2*e-13; accuracy = 0.898, sensitivity = 0.793, specificity = 0.949). The occurrence of at least one minor event during N3 was highly suggestive for DOA (p = 4*e-5; accuracy = 0.73, sensitivity = 0.733, specificity = 0.723). The "event distribution index" was statistically higher in DOA for total (p = 0.012) and major events (p = 0.0026). CONCLUSION: The stage and the relative time of occurrence of minor and major motor manifestations represent useful criteria to discriminate DOA from SHE episodes.

Clinical features of sleep-related hypermotor epilepsy in relation to the seizure-onset zone: A review of 135 surgically treated cases.

OBJECTIVES: Sleep-related hypermotor epilepsy (SHE), formerly nocturnal frontal lobe epilepsy, is characterized by abrupt and typically sleep-related seizures with motor patterns of variable complexity and duration. They seizures arise more frequently in the frontal lobe than in the extrafrontal regions but identifying the seizure onset-zone (SOZ) may be challenging. In this study, we aimed to describe the clinical features of both frontal and extrafrontal SHE, focusing on ictal semiologic patterns in order to increase diagnostic accuracy. METHODS: We retrospectively analyzed the clinical features of patients with drug-resistant SHE seen in our center for epilepsy surgery. Patients were divided into frontal and extrafrontal SHE (temporal, operculoinsular, and posterior SHE). We classified seizure semiology according to four semiology patterns (SPs): elementary motor signs (SP1), unnatural hypermotor movements (SP2), integrated hypermotor movements (SP3), and gestural behaviors with high emotional content (SP4). Early nonmotor manifestations were also assessed. RESULTS: Our case series consisted of 91 frontal SHE and 44 extrafrontal SHE cases. Frontal and extrafrontal SHE shared many features such as young age at onset, high seizure-frequency rate, high rate of scalp electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities, similar histopathologic substrates, and good postsurgical outcome. Within the frontal lobe, SPs were organized in a posteroanterior gradient (SP1-4) with respect to the SOZ. In temporal SHE, SP1 was rare and SP3-4 frequent, whereas in operculoinsular and posterior SHE, SP4 was absent. Nonmotor manifestations were frequent (70%) and some could provide valuable localizing information. SIGNIFICANCE: Our study shows that the presence of certain SP and nonmotor manifestations may provide helpful information to localize seizure onset in patients with SHE.

Sleep-Related Rhythmic Sound From the Vocal Cords: A Possible Atypical Form of NREM Parasomnia.

ABSTRACT: Sleep-related noises may have different features and etiologies. Here we report an atypical case of an adolescent with episodes of "sleep-related vocalization" occurring every night, especially during the first part of the night. The patient had moderate mental retardation and a dysfunctional dysphonia; she had no recollection of the episodes and complained exclusively of mild excessive daytime sleepiness. A video polysomnography recording documented two typical manifestations during non-rapid eye movement (NREM) sleep, characterized by the persistence of slow waves and without any electroencephalographic or breathing abnormalities. The quantified analysis of the acoustic features while confirming the rhythmic and stable characteristic of the sound suggests the involvement of the vocal fold vibration on its production. We interpreted these episodes as an atypical form of NREM parasomnia. A possible influence of the otolaryngologic abnormality can be hypothesized.

Seizure duration and latency of hypermotor manifestations distinguish frontal from extrafrontal onset in sleep-related hypermotor epilepsy.

Sleep-related hypermotor epilepsy (SHE) is an epilepsy syndrome that is characterized by the occurrence of sleep-related hypermotor seizures of variable complexity and duration. Seizures usually arise in the frontal lobe, but extrafrontal seizure onset zones are well described. To identify clinically relevant ictal features of SHE that could distinguish a frontal from an extrafrontal onset zone, we conducted a retrospective analysis of seizure characteristics in 58 patients with drug-resistant SHE (43 frontal and 15 extrafrontal) who underwent video-stereo-electroencephalographic recordings and became seizure-free after epilepsy surgery. We found that the mean duration of electrographic seizures and clinically observable ictal manifestations were significantly shorter in frontal SHE compared to extrafrontal SHE. The mean latency between electrographic seizure onset and the onset of hypermotor manifestations was also shorter in frontal SHE. Accordingly, a latency > 5 seconds between the first video-detectable movement (eg, eye opening or a minor motor event) and the onset of hypermotor manifestations yielded a sensitivity of 75% and a specificity of 90% for an extrafrontal onset, thereby indicating that specific ictal features in SHE can provide clinically useful clues to increase diagnostic accuracy in this syndrome.

NREM sleep parasomnias as disorders of sleep-state dissociation.

Non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) are fascinating disorders with mysterious neurobiological substrates. These conditions are common and often severe, with social, personal and forensic implications. The NREM parasomnias include sleepwalking, sleep terrors and confusional arousals - collectively termed disorders of arousal (DOAs) - as well as less well-known entities such as sleep-related sexual behaviours and eating disorders. Affected patients can exhibit waking behaviours arising abruptly out of NREM sleep. Although the individual remains largely unresponsive to the external environment, their EEG shows both typical sleep-like and wake-like features, and they occasionally report dreaming afterwards. Therefore, these disorders offer a unique natural model to explore the abnormal coexistence of local sleep and wake brain activity and the dissociation between behaviour and various aspects of consciousness. In this article, we critically review major findings and updates on DOAs, focusing on neurophysiological studies, and offer an overview of new clinical frontiers and promising future research areas. We advocate a joint effort to inform clinicians and the general public about the management and follow-up of these conditions. We also strongly encourage collaborative multicentre studies to add more objective polysomnographic criteria to the current official diagnostic definitions and to develop clinical practice guidelines, multidisciplinary research approaches and evidence-based medical care.

Drugs Used in Parasomnia.

Patient education and behavioral management represent the first treatment approaches to the patient with parasomnia, especially in case of disorders of arousal (DOA). A pharmacologic treatment of DOA may be useful when episodes are frequent and persist despite resolution of predisposing factors, are associated with a high risk of injury, or cause significant impairment, such as excessive sleepiness. Approved drugs for DOA are still lacking. The most commonly used medications are benzodiazepines and antidepressants. The pharmacologic treatment of rapid eye movement sleep behavior disorder is symptomatic, and the most commonly used drugs are clonazepam and melatonin.