Rapid eye movement sleep behaviour disorder: Past, present, and future.

This manuscript presents an overview of REM sleep behaviour disorder (RBD) with a special focus on European contributions. After an introduction examining the history of the disorder, we address the pathophysiological and clinical aspects, as well as the diagnostic issues. Further, implications of RBD diagnosis and biomarkers are discussed. Contributions of European researchers to this field are highlighted.

REM sleep, REM parasomnias, REM sleep behaviour disorder.

We review the literature on REM parasomnias, and their the underlying mechanisms. Several REM parasomnias are consistent with sleep dissociations, where certain elements of the REM sleep pattern emerge in an inadequate time (sleep paralysis, hypnagogic hallucinations and cataplexy) or are absent/partial in their normal REM sleep time (REM sleep without atonia, underlying REM sleep behavior disorder). The rest of REM parasomnias (sleep related painful erection, catathrenia) may have other still unclear mechanisms. REM parasomnias deserve attention, because in addition to disturbing sleep and causing injuries, they may shed light on REM sleep functions as well as the heterogeneous etiologies of parasomnias. One of them, REM sleep behavior disorder has special importance as a warning sign of evolving neurodegenerative conditions mainly synucleinopathies (some cases synucleinopathies themselves) and it is a model parasomnia revealing that parasomnias may have by autoimmune, iatrogenic and even psychosomatic etiologies.

Parasomnia overlap disorder, Parkinson's disease and subthalamic deep brain stimulation: three case reports.

BACKGROUND: Parasomnia overlap disorder (POD) is a distinct parasomnia and characterized by concomitant manifestation of rapid-eye-movement (REM)- and non-REM (NREM)-parasomnias. Although not uncommon among patients with Parkinson's disease, POD is often under-investigated. CASE PRESENTATION: This is the first report of patients with PD and features of POD that underwent deep brain stimulation. Our patients exhibited different outcomes of POD features after subthalamic deep brain stimulation. CONCLUSIONS: We expect that the reporting of these first patients will open the discussion about the need for more detailed and broad-spectrum assessments regarding parasomnias in PD patients that undergo deep brain stimulation. The implications of our observations are both clinical and neurobiological.

Recurrent Isolated Sleep Paralysis.

Recurrent isolated sleep paralysis has a 7.6% lifetime prevalence of at least one episode in the general population. Episodes resolve spontaneously and are benign. Sleep paralysis represents a dissociate state, with persistence of the rapid eye movement (REM)-sleep muscle atonia in the waking state. The intrusion of alpha electroencephalogram into REM sleep is followed by an arousal response and then by persistence of REM atonia into wakefulness. Predisposing factors include irregular sleep-wake schedules, sleep deprivation, and jetlag. No drug treatment is required. Patients should be informed about sleep hygiene. Cognitive behavioral therapy may be useful in cases accompanied by anxiety and frightening hallucinations.

Sleep Terrors.

Sleep terrors, categorized under disorders of arousal, more prevalent in pediatric population, generally are self-limited but sometimes can persist or occur in adulthood. These are primed by factors enhancing homeostatic drive on backdrop of developmental predisposition and are precipitated by factors increasing sleep fragmentation resulting in dissociated state of sleep with some cerebral regions showing abnormal slow wave activity and others fast activity. This phenotypically evolves into abrupt partial arousal with individual arousing from N3 or N2 sleep with behaviors representing intense fear such as crying with autonomic hyperactivity. There is no recollection of the event, and lack of vivid dream mentation although fragmented imagery may be noted. Behavioral management is of prime importance including addressing precipitating factors, family reassurance, safety measures, and scheduled awakenings. Pharmacologic agents such as clonazepam and antidepressants are used infrequently in case of disruptive episodes.

The parasomnia defense in sleep-related homicide: A systematic review and a critical analysis of the medical literature.

This review critically analyzes the forensic application of the Parasomnia Defense in homicidal incidents, drawing from medical literature on disorders of arousal (DOA) and rapid-eye-movement sleep behavior disorder (RBD). A systematic search of PubMed, Scopus, Embase, and Cochrane databases was conducted until October 16, 2022. We screened English-language articles in peer-reviewed journals discussing murders committed during sleep with a Parasomnia Defense. We followed PRISMA guidelines, extracting event details, diagnosis methods, factors influencing the acts, perpetrator behavior, timing, motives, concealment, mental experiences, victim demographics, and court verdicts. Three sleep experts evaluated each case. We selected ten homicides, four attempted homicides, and one homicide/attempted homicide that met inclusion/exclusion criteria. Most cases were suspected DOA as unanimously confirmed by experts. RBD cases were absent. Among aggressors, a minority reported dream-like experiences. Victims were primarily female family members killed in or near the bed by hands and/or with sharp objects. Objective sleep data and important crime scene details were often missing. Verdicts were ununiform. Homicides during DOA episodes, though rare, are documented, validating the Parasomnia Defense's use in forensics. RBD-related fatal aggression seems very uncommon. However, cases often lack diagnostic clarity. We propose updated guidelines to enhance future reporting and understanding of such incidents.

Sleep-Related Dissociative Disorders.

In sleep-related dissociative disorders, phenomena of the psychiatrically defined dissociative disorders emerge during the sleep period. They occur during sustained wakefulness, either in the transition to sleep or following an awakening from sleep. Behaviors during episodes vary widely, and can result in injury to self or others. Daytime dissociative episodes and a background of trauma are almost always present; there is typically major co-existing psychopathology. Diagnosis is based on both clinical history and polysomnography; differential diagnosis primarily involves other parasomnias and nocturnal seizures. Information available about treatment is limited; in a few reported cases, psychological interventions have proven effective.

The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians.

Background: Damaging coding variants in GBA1 are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies. Recently, a population-specific non-coding variant (rs3115534) was found to be associated with PD risk and earlier disease onset in individuals of African ancestry. Objectives: To investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD. Methods: We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. The GBA1 rs3115534 risk variant status was imputed from previous genotyping for all. Symptoms of RBD were assessed with the RBD screening questionnaire (RBDSQ). Results: The non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (Beta = 0.3640, SE = 0.103, P =4.093e-04), as well as after adjusting for PD status (Beta = 0.2542, SE = 0.108, P = 0.019) suggesting that this variant may have the same downstream consequences as GBA1 coding variants. Conclusions: We show that the non-coding GBA1 rs3115534 risk variant is associated with increased RBD symptomatology in Nigerians with PD. Further research is required to assess association with polysomnography-defined RBD.

Electroencephalogram abnormalities in patients with NREM parasomnias.

OBJECTIVE: Electroencephalographic (EEG) changes in patients with NREM parasomnias (NRP) occur in sleep architecture as changes in slow wave sleep or cyclic pattern, which are not considered abnormal. However, abnormalities in EEG in these patients have recently been reported, indicating that EEG patterns in NRPs are not definitive. Moreover, most of the polysomnography (PSG) findings in NRP patients were reported in the adult population requiring data from pediatric population to avoid bias in conclusion. METHODS: In sum, 39 patients with a NRP were undergone comprehensive assessments including a PSG with additional EEG montages. EEG recordings were evaluated in patients without a history of epilepsy and further compared between pediatric and adult patients. RESULTS: Twenty-three (59%) of the patients were pediatric and 77% were male. The mean age was 18.4 (±13.1) years. Of the patients, 19 (49%) had somnambulism, 13 (33%) had confusional arousal and seven (18%) had sleep terrors. Macrostructure of sleep detected by PSG was normal in all patients. After excluding 11 (28%) patients with a positive history of epilepsy, seven (25%) of 28 showed EEG abnormalities within K-complexes in NREM-II stage, six of whom were pediatric patients compared to only one adult (p < 0.05). CONCLUSION: This study showed that patients with NRP may display EEG abnormalities in NREM-II stage. These abnormalities were more frequent in pediatric patients compared to adults. In NRP patients, utmost care should be taken in EEG evaluations to prevent false diagnosis of epilepsy.

Cotard parasomnia: le délire de negation that occur during the sleep-wake dissociation?

None: Unpleasant dreamlike mentation can occur during non-rapid eye movement parasomnias, leading to associated panic attacks. The mentations are rarely remembered and are likely underreported. However, they may lead to significant personal distress and, if not addressed, may contribute to poorer clinical outcomes. Cotard le délire de negation are very rare nihilistic delusions, historically described with psychotic disorders. Their association with a variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard parasomnia during which distinct states of consciousness defined by nihilistic ideation occurred. Patients described believing they are dead or dying, while unable to perceive or experience their bodies in whole, or in part, as their own. A source analysis of the electroencephalographic fingerprint of these mentations suggests right-hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience network and the default mode network, is argued.

Cotard's Parasomnia: Le Délire de Negation that occur during the Sleep-Wake Dissociation?

NONE: Unpleasant dreamlike mentation can occur during NREM parasomnias, leading to associated panic attacks. The mentations are rarely remembered, and are likely underreported. However, they may lead to significant personal distress, and if not addressed, may contribute to poorer clinical outcomes. Cotard's 'Le Délire de Negation', are very rare nihilistic delusions, historically described with psychotic disorders. Their association with variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard's parasomnia during which distinct states of consciousness defined by nihilistic ideation are reported. Patients described believing to be dead or dying, whilst unable to perceive or experience their bodies in whole, or in part, as their own. The source analysis of electroencephalographic fingerprint of these mentations suggests right hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience and the default-mode-network is argued.

Apathy in Parkinson's disease with REM sleep behavior disorder.

OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) in patients with Parkinson's disease (PD) is associated with increased risk of non-motor symptoms. However, the association between RBD and apathy in PD remains unclear. AIMS: To compare the prevalence and severity of apathy symptoms in PD patients with RBD (PD-RBD+) and without (PD-RBD-). In addition, we explored the association between apathy, depressive symptoms and RBD, taking into consideration the concomitant influence of demographic, disease- and therapy-associated variables. METHODS: Sixty-four PD patients were evaluated with systematic motor (unified Parkinson's disease rating scale, UPDRS-III) and non-motor assessments. The diagnosis of RBD was based on the international consensus criteria using video-polysomnography. Apathy, sleepiness, depressive symptoms and cognitive performance were assessed using the Starkstein apathy (SAS, cut-off = 14), the Epworth sleepiness (ESS), the Hamilton depression (HAM-D, cut-off = 9) scales and the mini-mental state examination (MMSE), respectively. RESULTS: Among 64 patients, 26 (40%) had RBD. In the PD-RBD+ group, apathy symptoms were more frequent (52% vs 42%) and more severe (14.3 ±â€¯5.8 vs 11.2 ±â€¯4.9, p < 0.05), especially in the females (17.3 ±â€¯6.0 vs 11.4 ±â€¯5.8 in males, p < 0.05) compared to the PD-RBD- group. A high percentage of patients, especially in the PD-RBD+ group (53%), had isolated apathy without increased depressive symptoms. Increased depressive symptoms were also more frequent (50% vs 20%) and more severe in the PD-RBD+ group. The two groups were comparable in respect to demographic and clinical characteristics. CONCLUSIONS: In PD, RBD is associated with isolated apathy and increased severity of depressive symptoms, independent of medication, motor and other non-motor symptoms. Potential mechanisms underlying this association are discussed.

Therapeutic Symptomatic Strategies in the Parasomnias.

PURPOSE OF REVIEW: The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias. RECENT FINDINGS: Recent pathophysiological findings about sleep structure in parasomnias helped understanding several drug mechanisms of action. Serotoninergic theory accounts for the effect of serotoninergic drugs. Study about spectral analysis of sleep showed the effect of clonazepam on spectral bands. Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders. A series of therapeutic strategies were analyzed and compared. Benzodiazepines, antidepressant drugs, and L-5-hydroxytryptophan may be beneficial in DOA. SSRI and topiramate are effective in SRED. RBD responds to clonazepam, melatonin, and to a lesser extent to dopaminergic and anticholinergic agents. Prazosin and cannabinoids are effective in nightmare disorder. Sleep paralysis may respond to antidepressant agents. Tricyclic antidepressant may be effective in sleep-related hallucinations and exploding head syndrome. Sleep enuresis may be successfully treated with desmopressin, anticholinergic drugs, and imipramine.

Two Cases of Sleep-Related Eating Disorder Responding Promptly to Low-Dose Sertraline Therapy.

ABSTRACT: We report two cases of adult males with sleep-related eating disorder (SRED), with durations of 3 and 7 years, and without associated psychiatric history. In both cases, the use of low-dose (25 mg) sertraline taken at bedtime resulted in immediate, full and sustained resolution of symptoms at the latest follow-ups. The sertraline efficacy was of particular benefit for the patient reported on in case 2 who was a commercial airline pilot subjected to a highly restricted list of Federal Aviation Administration-approved medications. Risk factors for SRED included smoking cessation and work-related stress in case 1, and a history of sleepwalking and work-related circadian disruptions and partial sleep deprivations in case 2. Sertraline therapy of SRED is considered within a review of all current pharmacologic therapies of SRED.

Sexsomnia: A Specialized Non-REM Parasomnia?

Introduction: To describe patients with sexsomnia and to contrast their clinical and sleep measures with those of healthy controls and sleepwalkers. Aims and Methods: Subjects referred for sexsomnia and for sleepwalking/night terror were interviewed, completed the Paris Arousal Disorder Severity Scale (PADSS), and were monitored 1-2 nights with video-polysomnography. Results: Seventeen patients (70.6% male, aged 17-76 years) had sexsomnia, with amnestic fondling of the bed partner (n = 11), complete sexual intercourse (n = 8), masturbation (n = 8), and spontaneous orgasm (n = 1). The sexual behaviors were more direct during sleep than during wakefulness (n = 12), leading to 6 sexual assaults, including intra-conjugal rape (n = 3), assault of a family member (n = 2), rape of a friend (n = 1), and forensic consequences (n = 2). In 47% of sexsomnia patients, there was a history or current occurrences of sleepwalking/night terrors. Patients with sexsomnia had more N3 awakenings than healthy matched controls and the same amount as regular sleepwalkers. Half of them presented evidence of cortico-cortical dissociation, including concomitant slow (mostly frontal) and rapid (mostly temporal and occipital) electroencephalography (EEG) rhythms, with concomitant N3 penile erection in 1 case. Of 89 sleepwalkers, 10% had previous episodes of amnestic sexual behaviors, with a higher PADSS-A score and a trend of a higher total PADSS score than the 80 sleepwalkers without sexsomnia. Conclusion: In this single-center series, we confirmed the male predominance of sexsomnias and its potential for severe clinical and forensic consequences. The results suggest a continuum of regular sleepwalking, sleepwalking with occasional sexsomnia, and quasi-exclusive sexsomnia.

Fluctuations between sleep and wakefulness: wake-like features indicated by increased EEG alpha power during different sleep stages in nightmare disorder.

Although a growing body of research indicates that frequent nightmares are related to impaired sleep regulation, the pathophysiology of nightmare disorder is far from being fully understood. We examined the relative spectral power values for NREM and REM sleep separately in 19 individuals with nightmare disorder and 21 healthy controls, based on polysomnographic recordings of the second nights' laboratory sleep. Nightmare subjects compared to controls exhibited increased relative high alpha (10-14.5Hz) and fronto-central increases in high delta (3-4Hz) power during REM sleep, and a trend of increased fronto-central low alpha (7.75-9Hz) power in NREM sleep. These differences were independent of the confounding effects of waking emotional distress. High REM alpha and low NREM alpha powers were strongly related in nightmare but not in control subjects. The topographical distribution and spectral components of REM alpha activity suggest that nightmare disordered subjects are characterized by wake-like electroencephalographic features during REM sleep.