REM sleep-related parasomnias …

Sleep Disorders

Updated 08.17.2024
Released 05.26.2020
Expires For CME 08.17.2027

REM sleep-related parasomnias

Authors: Federica Provini MD, Luca Baldelli MD

See Contributor Disclosures

Editor: Antonio Culebras MD FAAN FAHA FAASM

REM sleep-related parasomnias

In This Article

Quick Link

Introduction

Overview

Parasomnias are common undesirable physical events or experiences during entry into sleep, within sleep, or during arousals from sleep due to inappropriate activation of the cognitive process or physiological systems, such as the motor or autonomic nervous system. When episodes are frequent, they can result in sleep disruption and injuries, with adverse health or psychosocial consequences for the patients, bed partners, or both. According to the International Classification of Sleep Disorders (ICSD-3-TR), parasomnias are divided into four categories: (1) NREM-related parasomnias, including disorders of arousal (confusional arousals, sleep terror, and sleepwalking) and sleep-related eating disorder; (2) REM-related parasomnias, including nightmare disorder, recurrent isolated sleep paralysis, and REM sleep behavior disorder; (3) other parasomnias, including exploding head syndrome, sleep-related hallucinations, sleep-related urologic dysfunction, parasomnia unspecified, parasomnia due to a medication or substance, and parasomnia due to a medical disorder; and (4) isolated symptoms and normal variants, including sleep talking (01). In this article, the authors describe the characteristics of REM-related parasomnias, suggesting the key points for a decisive diagnostic workup.

Key points

	• Parasomnias are common in the general population.
	• The large number of parasomnias underscores that sleep is not simply a quiescent state but can involve experiences or behaviors that are more or less complex.
	• Some parasomnias are usually benign phenomena (eg, isolated sleep paralysis); other parasomnias (eg, REM sleep behavior disorder) are true diseases that could lead to injuries affecting not only the patient but also their bed partner.
	• Parasomnias must be distinguished from other sleep-related motor behaviors (eg, epileptic seizures arising from sleep).
	• The evaluation of parasomnias depends on an accurate history and clear description of the events.
	• Video-polysomnography remains the most useful support for the final diagnosis.

Historical note and terminology

Parasomnias have attracted the interest of writers and scholars for centuries. Their sometimes dramatic manifestations have been described by many. Miguel de Cervantes described a typical REM sleep behavior disorder episode in which Don Quixote shouts and vigorously attacks some wineskins while dreaming that he is fighting a giant (25). The description of the monstrous metamorphosis of Gregor Samsa, the protagonist of The Metamorphosis by Kafka, has been interpreted as a nightmare (41). Sleep paralysis plays a role in the writing of great novelists, including Dostoevsky in The Brothers Karamazov and Maupassant (The Horla) (52). In the fine arts, Johann Heinrich Füssli’s 1775 painting “The Nightmare” may reflect sleep paralysis with a hypnagogic hallucination (52).

Clinical manifestations

Presentation and course

According to the International Classification of Sleep Disorders (ICSD-3-TR) REM-related parasomnias include nightmare disorder, recurrent isolated sleep paralysis, and REM sleep behavior disorder. REM-related parasomnias generally occur in the last half of the night when REM sleep predominates, and, in contrast to NREM parasomnias, no confusion or disorientation is present.

Nightmares are characterized by extremely dysphoric frightening dreams, usually involving threats to survival, security, or physical integrity associated with precise recalled details. Nightmares are experienced occasionally by many persons during their lifetime, occurring as a primary complaint without other comorbidities or in the context of other sleep, neurologic, or psychiatric disorders or systemic diseases. Nightmare disorder refers to nightmares causing clinically significant distress or impairment in social, occupational, or other important areas of functioning (21). According to the International Classification of Sleep Disorders (ICSD-3-TR) the diagnosis of nightmare disorder consists of the following three criteria: (1) repeated occurrence of extended, extremely dysphoric, and well-remembered dreams that usually involve threats to survival, security, or physical integrity; (2) on awakening from the dysphoric dreams, the person rapidly becomes oriented and alert; and (3) the dream experience or the sleep disturbance produced by awakening from it causes clinically significant distress or impairment in social, occupational, or other important areas of functioning (01).

Sleep paralysis is a relatively common but under-researched phenomenon, with terms for sleep paralysis existing in over 100 cultures (eg, in Hong Kong it is called “the ghost oppression phenomenon”) (52; 50). Sleep paralysis occurs when the atonia of REM sleep persists into wakefulness; thus, patients awaken finding themselves completely paralyzed and frequently feeling as if they are in danger of imminent death. Similar to the atonia in REM sleep, muscle atonia during sleep paralysis includes striated muscles under voluntary control except for the diaphragm, external eye muscles, and stapedius (52). The experience of a full-body paralysis despite subjective alertness is overwhelmingly unpleasant and frightening, especially when occurring for the first time and when accompanied by feelings of suffocation (06; 50). Sleep paralysis can be accompanied by visual and auditory hallucinations such as a sense of an evil presence (known as intruder hallucinations), pressure felt on the chest (incubus hallucinations), and illusory feelings of movement (vestibular-motor hallucinations) (14). The episodes last from a few seconds to several minutes disappearing spontaneously or on external stimulation. Sleep paralysis can occur as an isolated sporadic phenomenon, or it may be associated with narcolepsy.

According to the International Classification of Sleep Disorders (ICSD-3-TR), the diagnostic criteria for recurrent isolated sleep paralysis, all of which must be met, include: (1) a recurrent inability to move the trunk and all of the limbs at sleep onset or on awakening from sleep; (2) each episode lasts seconds to a few minutes; (3) episodes cause clinically significant distress including bedtime anxiety or fear of sleep; and (4) the disturbance is not better explained by another current sleep disorder (especially narcolepsy), mental disorder, medical disorder, or medication or substance use.

REM sleep behavior disorder (RBD) is characterized by REM-related motor episodes during which the patient presents more or less purposeful gestures enacting attack or defense reactions, sometimes associated with emotional expressions of joy, laughter, or sorrow (19). In fact, due to the lack of the normal muscle atonia of REM sleep, the patients are able to “act out” their dreams (44).

REM sleep behavior disorder

REM sleep behavior disorder: framed pictures show examples of typical dream-enacting behaviors in REM sleep behavior disorder such as protecting from an aggressor, arguing, pointing someone/something, running, and even jumping awa...

During the episodes, patients can be accidentally violent, and bed partners are frequently unintentionally injured (44; 01). In RBD, the main themes collected in the dream recall were usually violent and aggressive attacks by people or animals, not matching with personality features during wakefulness (49; 18). Almost half of the patients are unaware of their dream-enactment behaviors, with 70% of them reporting good sleep quality. In most cases, bed partners are essential to convince patients to seek medical help (19). REM sleep behavior disorder can be isolated or associated with the use of various substances or with a heterogeneous group of general medical conditions, including neurologic disorders, mostly a-synucleinopathies (52; 28; 07).

According to the International Classification of Sleep Disorders (ICSD-3-TR), the diagnostic criteria for REM sleep behavior disorder, all of which must be met, include: (1) repeated episodes of sleep-related vocalization or complex motor behaviors; (2) these behaviors are documented by video-polysomnography to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep; (3) polysomnographic recording demonstrates REM sleep without atonia; (4) the disturbance is not better explained by another current sleep disorder or mental disorder.

Prognosis and complications

Nightmares and sleep paralysis, when occurring frequently or involving intense negative emotional components, can induce intense fear and anxiety associated with poor sleep, impairing well-being and social functioning (50).

Nightmares and insomnia are connected, being the dreams of patients with insomnia usually characterized by more negative content and effects. For these reasons, nightmares and insomnia may be mutually aggravating; insomnia might increase the likelihood of experiencing nightmares, and nightmares can, in turn, lead to sleep loss and nonrestorative sleep (13).

Recurrent nightmares are the most defining symptom of posttraumatic stress disorder (02). The association between nightmares and suicide has yielded different results, but the incidence of depression seems higher among those who suffer from nightmares.

As a complication of REM sleep behavior disorder, the patient or bed partner may be unintentionally injured (34).

Isolated REM sleep behavior disorder can occur many years before the onset of motor or other non-motor symptoms of parkinsonian syndromes, such as multiple system atrophy or Lewy body dementia (28; 36; 58). In a large multicenter study of 1280 patients from 24 different centers, the overall conversion rate from isolated REM sleep behavior disorder to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after a 12-year follow-up. The rate of phenoconversion was significantly increased if motor symptoms, olfactory deficit, mild cognitive impairment, erectile dysfunction, an abnormal DAT scan, color vision abnormalities, and constipation were present (29).

RBD comorbid with traumatic brain injury and posttraumatic stress disorder may be associated with more advanced neurologic symptoms related to an evolving neurodegenerative process, including more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to isolated RBD (16).

When RBD is present in patients with Parkinson disease, it could define a more severe phenotype, with faster cognitive decline and motor progression, the presence of impulse control disorders, and specific functional and structural brain-imaging features (more severe nigrostriatal dopaminergic impairment, altered regional homogeneity, and connectivity in the cerebellum and visual-motor relevant cortex) (17; 40; 32; 59; 15). Resting-state functional MRI (rs-fMRI) showed global connectivity largely preserved in iRBD and individuals with Parkinson disease, but both disease groups displayed altered local connectivity mainly in the motor network; temporal cortical regions, including the limbic system; and the visual system (26).

Also, a greater severity of REM sleep without atonia at polysomnography is associated with an increased risk for poor cognitive performance and depressive mood in patients with REM sleep behavior disorder (20).

The impairment of 24-hour blood pressure control in patients with isolated RBD as well as in de novo Parkinson disease, consisting of reduced amplitude of nocturnal dipping and increased frequency of non-dipping status, could have possible implications for cardiovascular morbidity and mortality in these patients (54).

Clinical vignette

A 72-year-old woman presented with a 4-year history of nocturnal injuries and terrifying dreams. The woman’s history comprised well-controlled diabetes type 2 and left mammary carcinoma at 61, surgically treated. Family history was unremarkable apart from reported essential tremor in the sister and in the grandmother.

Almost every night the patient experienced vivid dreams full of violent content, frequently involving threatening situations where she was being attacked or had to flee from danger. The patient’s daughter who slept in the contiguous room reported movements and vocalizations mimicking the contents of those dreams, including punching, kicking, hitting the nightstand, and throwing herself out of bed. These episodes were more frequent in the latter part of the night. Serious traumatisms also happened. “On one night I dreamt to be chased by a flock of rampaging bulls, I tried to jump behind a rock to protect myself…I suddenly woke up with intense pain and blood covering my face, I threw myself out of the bed, broking my nose by cracking the glass nightstand,” the patient reported. Neurologic examination was negative apart from a slight postural tremor in both hands. Video-polysomnography documented persistent muscular tone on mylohyoideus muscle and increment of phasic muscular activity in limbs during REM sleep. Moreover, during REM sleep, the patient started to abruptly move the left hand and shouted as she was arguing with someone. Based on the characteristic history, on polygraphic findings, and in the absence of any previous neurologic condition, she was diagnosed with isolated REM sleep behavior disorder. Pharmacologic treatment was suggested. The patient started clonazepam 1 mg taken 20 minutes before going to bed. At a follow-up visit 4 months later, the patient reported improvement of the symptoms, in particular, intense dream-enacting disappeared, and no more traumas occurred; unpleasant dreams also reduced to two to three per month.

Biological basis

Etiology and pathogenesis

Nightmares can occur as a primary complaint or in the context of other sleep (eg, insomnia), psychiatric context (eg, anxiety, depression, schizophrenia), neurologic diseases (eg, epilepsy), or medication or substance intake. The etiology of nightmares is best explained by a disposition-stress model hypothesizing that both nightmare frequency and neuroticism are significantly related to nightmare distress (21). Other research groups have underlined that the etiology of nightmare disorder may be influenced by increased hyperarousal that accumulates during the day and is maintained at night, associated with an impaired fear extinction (06).

The causes of sleep paralysis are likely to be multifactorial, including a moderate genetic influence and recurrent experience of threatening or traumatic events (14). Studies suggested an increased prevalence of sleep paralysis in patients with obstructive sleep apnea, nocturnal leg cramps, and psychiatric disorders, especially posttraumatic stress disorder, anxiety, and panic disorder. Very little experimental work into the underlying neurophysiology of sleep paralysis has been performed. However, it appears that episodes are linked with sleep disruption and are particularly associated with sleep onset REM periods (SOREMPs) (14). At a neurobiological level, the paralysis associated with REM sleep is believed to be regulated by the GABA and glycine neurotransmitter systems, which are important in inhibiting motor neurons during REM sleep, thus, contributing to muscle atonia. What is currently unknown is why some people regain waking levels of consciousness during REM sleep, resulting in an episode of sleep paralysis (14).

REM sleep behavior disorder can manifest as isolated or can be associated with a heterogeneous group of conditions, including alpha-synuclein neurodegenerative disorders, narcolepsy, paraneoplastic or autoimmune disorders, central nervous system lesions (eg, tumors or stroke), antidepressants or other medications, drug withdrawal states, and toxic metabolic states (50; 07).

In REM sleep behavior disorder, the patients have lost the ability to maintain the skeletal muscle atonia due to a primary or secondary effect on generating this REM attribute.

Dream enactment behavior (polysomnogram)

This polysomnogram of a patient with REM sleep behavior disorder illustrates dream enactment behavior occurring during REM sleep. (Contributed by Dr. Bradley Vaughn.)

REM sleep behavior disorder can be produced in animals by selective inactivation of the sublateral dorsal nucleus in the pontine tegmentum and GABAergic/glycinergic in ventromedial medullary inhibitory neurons (56). Neuropathological and pharmacological damage to the same nuclei in humans can lead to REM sleep behavior disorder manifestation. Beyond the brainstem, neuroimaging documented structural and functional changes involving the nigrostriatal system, limbic system, and cortex, suggesting that REM sleep behavior disorder is a multi-systemic neurodegenerative process (57; 11).

Although no association between rare heterozygous genetic variants of parkinsonism was found in patients with REM sleep behavior disorder (39), polygenic disease burden may play a role (55). Altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in REM sleep behavior disorder pathophysiology (37). Measuring biological aging using DNA methylation-based epigenetic clocks, patients with isolated REM sleep behavior disorder tended to be epigenetically older than controls, suggesting that accelerated aging characterizes prodromal neurodegeneration (05).

REM sleep behavior disorder linked to narcolepsy has been insufficiently characterized, leaving several issues unsolved. In particular, it is still debated whether REM sleep behavior disorder is an intrinsic feature of narcolepsy or an associated feature with a still unclear pathophysiology (03).

In community-based studies of older adults, lower education, presence of head injury, atrial fibrillation, hyperlipidemia, constipation, olfactory disturbance, imbalance, use of alcoholic beverages, selective serotonin reuptake inhibitors, nonoccupational exposure to pesticides, and benzodiazepine use were associated with a higher likelihood of having probable REM sleep behavior disorder (33; 60).

Prevention

The primary prevention of nightmares and sleep paralysis is based on reducing stress, improving sleep hygiene, ensuring regular and adequate sleep routines, and avoiding sleep loss or deprivation and cognitive-impairing substances (52). Acute withdrawal from therapy with REM sleep suppressant medications (eg, clonidine, antidepressants, or anxiolytic agents) can result in REM sleep rebound, vivid dreaming, and nightmares. In individuals with events as a symptom of another sleep disorder, such as obstructive sleep apnea, REM sleep parasomnia disappears after treatment of the primary sleep disorder.

Studies have documented that more than 60% of nightmare sufferers had never discussed nightmares with a clinician. Given their clinical relevance, it is necessary to improve the identification and treatment of nightmare disorder. It is recommended that questions about nightmares should be included when taking a sleep history and that patients should be offered an effective treatment. A new multidimensional scale, the nightmare severity index (NSI), which evaluates the frequency, emotional impact, diurnal impact, and nocturnal impact of nightmares, seems to be a promising and valuable tool for clinical practice, demonstrating good acceptability, internal validity, and the ability to assess nightmare severity (22).

REM sleep behavior disorder observed in patients on antidepressant treatment was initially classified as “medication-induced secondary REM sleep behavior disorder” (45). However, later studies showed that cessation of antidepressant treatments did not resolve the REM sleep behavior disorder, considering the development of the disorder with antidepressants as a possible early sign of an underlying neurodegenerative disease.

The genetic backgrounds of REM sleep behavior disorder, Parkinson disease, and Lewy body dementia only partially overlap, and larger REM sleep behavior disorder studies will be required to better elucidate the genetic background of the disorder. The lysosomal pathway, and more specifically the GBA pathway, could be a crucial target for therapeutic development targeting REM sleep behavior disorder (30).

Differential diagnosis

Confusing conditions

The differential diagnosis of REM parasomnias depends largely on the symptoms and signs associated with the particular disorder. Evaluation requires special emphasis on a detailed description of the nocturnal events, including age at onset, the frequency of the episodes during the night, the timing, the presence of stereotypic movements, the response to intervention, and the recall of the event. Conditions associated with nocturnal pain may be a factor, particularly in infants or developmentally disabled individuals who cannot describe their symptoms. The primary differential features can be found in Table 1.

Table 1. Differences Between REM Sleep Parasomnias Features

Feature	Nightmare	Sleep paralyses-related hypnopompic hallucination	Rapid eye movement sleep behavior disorder
Timing	Usually in the latter part of the night	Awakening at late night or in the morning	At least 60-90’ after sleep onset. Usually in the latter part of the night.
Stage	REM NREM also in post-traumatic nightmares	REM intruding into wakefulness	REM
Sleep structure	Normal Fragmented by awakenings	Normal	Normal REM sleep without atonia
Duration	Up to many minutes	Seconds-minutes	Tens of seconds
Frequency (per night)	One to many per night	Usually one per night	Usually 1-4 per night
Motor features	None	REM-like muscle paralysis	Violent behaviors and vocalizations mimicking the content of the dream, including punching, or kicking Nonviolent elaborate behaviors may also occur
Mentation content	Themes related to fear and involving a direct threat to mental/physical integrity	Single or multisensory Visual: kaleidoscopically phenomena, light flashes, lifelike images Auditory: voices, steps Somatic: body distortions, entities climbing over the body	Complex “dream tale”. Dream content usually involve (active) defense against aggression
Emotional load	Very high. Fear, anger, sadness, helplessness, anxiety, and frustration	Usually very high. Unpleasant and frightening	High. Especially fear and anger
Bizarreness	Very bizarre	Very bizarre	Usually not bizarre
Spatial reference	Self-centered	Outside the subject. Images, sounds, silhouettes have no or little interaction with the subject	Self-centered. The actions performed are usually hetero directed
Focalization*	Internal	Internal	Internal
Autonomic activation	Accelerated heart and respiratory rates usually precede the awakenings	Accelerated heart and respiratory rates when frightening	Blunted, tachycardia may not accompany the impressive movements
*The term focalization, used in modern narratology, describes the kind of perspective from which the events of a story are witnessed. The term “zero focalization” corresponds to an omniscient narrator, where the narrator knows more than the character, or more exactly, says more than any of the characters knows: narrator (the dreamer) > character (the subject of the dream). In “internal focalization”, the narrator knows/says only what a given character knows (narrator = character). In the third case “external focalization”, the narrator knows/says less than the character knows (narrator < character). Modified with permissions from (06) under Creative Commons Attribution 4.0 International License.

Nightmares and nightmare disorder must be distinguished from REM sleep behavior disorder, sleep terrors, hypnagogic hallucinations with or without sleep paralysis, and nocturnal panic attacks. Unlike patients with REM sleep behavior disorder, patients with nightmare disorder may vocalize or move minimally during their nightmares, but complex motor behaviors paralleling dream content are usually lacking. In addition, patients with nightmare disorder exhibit physiological REM sleep muscle atonia during polysomnography. Sleep terrors emerge from stage 3 NREM sleep with shouting and high autonomic activation. In contrast to sleep terror, in nightmares, no confusion or disorientation is present, and the highly disturbing dream content frequently contrasts strikingly with relatively minor autonomic activation (except for the increase of autonomic tone before the awakenings) and no acting out of the nightmare (06). Hallucinations and sleep paralysis may be described as “nightmares,” but they specifically occur at sleep onset and offset, and the paralysis affects the whole body. Nocturnal panic attacks are not associated with detailed mental imagery. Severe sleep apnea may be associated with disagreeable sleep-associated perceptions or images that resolve with the apnea treatment (04).

Sleep paralysis should be differentiated from epilepsy, and this can be achieved by performing vPSG or video-EEG with a recording of an episode (52). Concerning the possibly related hallucinations, their content can be distinguished from other sleep disorders as consisting of an emotionally loaded imagination set against an existing background as one part of a perceived scene (06).

REM sleep behavior disorder needs to be distinguished from disorders of arousal. In contrast to REM sleep behavior disorder, sleepwalking and night terrors are more frequent in children and rarely appear de novo in middle-aged or elderly subjects. Confusion and amnesia for the episodes, which are common features of NREM parasomnias, are not seen in patients with REM sleep behavior disorder (04). Dream-enacting behaviors could also appear in severe obstructive sleep apnea, and nocturnal epileptic seizures may also mimic REM sleep behavior disorder. In both cases, polysomnography will be mandatory to make the diagnosis (52; 06).

Diagnostic workup

The diagnostic workup is highly contingent on the type and frequency of symptoms. Many parasomnias can be diagnosed based on the history, including a clear description of the events from witness and physical examination. In general, one can differentiate parasomnias by looking for key distinguishing features. Yet the clinician should distinguish between a “benign” parasomnia and a nocturnal event that requires further investigation. Patients should be considered for polysomnographic evaluation if the presentation is atypical for a parasomnia or if:

	• the events are injurious or have significant potential for injury
	• the events significantly disturb the patient’s home life
	• the events begin or persist at an unusual age
	• the events appear stereotypical or repetitive or unusually frequent
	• the patient complains of excessive daytime sleepiness or insomnia or has symptoms suggestive of sleep apnea or periodic limb movements.

Sleep laboratory evaluations may include one or two nights of recording in a laboratory with personnel experienced in studying patients with parasomnias or nocturnal epileptic seizures. Simultaneous polysomnographic-audio-video monitoring is essential for such recordings, often with additional physiological measures beyond the minimum required for standard polysomnography (38). Prompting the patient to make audio-video recordings at home may facilitate the diagnosis, often adding details missed in verbal descriptions given by relatives. Patients should be considered for video-EEG monitoring if the events are stereotyped or repetitive, frequently occur (minimum of one event per week), or have not responded to medication trials, and the history is suggestive of potentially epileptic events (38). Obstructive sleep apnea that requires CPAP may reduce the diagnostic accuracy for REM sleep behavior disorder by a video polysomnogram. False-negative results were probably due to frequent electromyographic artifacts or severe sleep disruption from apneic events during REM sleep (31).

Overnight polysomnography is not routinely used to assess nightmare disorder but may be appropriately performed to exclude other parasomnias or sleep-disordered breathing. Sleep recordings during nightmares occasionally show abrupt awakenings from REM sleep preceded by accelerated heart and respiratory rates.

Sleep paralysis should be considered by clinicians when diagnosing sleep disorders, especially in narcolepsy and those exhibiting insomnia symptoms (14). Sleep paralysis should be assessed more frequently in psychiatric patients, particularly those presenting with posttraumatic stress disorder and anxiety disorders. In patients who experience severe episodes of sleep paralysis, it is necessary to consider the patient's mental and physical health and the quality of sleep as possible sleep-paralysis-related factors (14).

Video-polysomnography is essential for diagnosing REM sleep behavior disorder (01; 53). The RBD Symptom Severity Scale (RBDSSS), developed by the International RBD Study Group, is a tool to assess the severity of clinical symptoms by means of eight questions assessing the frequency and severity and impact of dream content, vocalizations, movements, and injuries associated with RBD (10).

Prodromal REM sleep behavior disorder is a stage in which symptoms and signs of evolving REM sleep behavior disorder are present but do not yet meet the established diagnostic criteria for REM sleep behavior disorder. However, the boundary between prodromal and definite REM sleep behavior disorder is still unclear, as pointed out by Cesari and colleagues (09). Actigraphy has also been proposed as a reliable screening instrument for REM sleep behavior disorder and is potentially useful in the general population (51). Automatic methods based on artificial intelligence may also significantly contribute to future advancements in the field of REM sleep behavior disorder.

Management

Recurrent nightmares may also be a deleterious effect of various drugs, such as antidepressants, antihypertensives (beta blockers, alpha-adrenergic receptor agonists, enalapril, losartan, verapamil), dopamine receptor agonists, cholinesterase blockers (donepezil, rivastigmine, tacrine), varenicline (a nicotinic acetylcholine blocker), and ganciclovir. The abrupt withdrawal of REM sleep-suppressive agents (antidepressants, benzodiazepine, barbiturate, ethanol) or the end-of-night REM sleep rebound after using short-acting hypnotics, such as zolpidem, can promote nightmares (04). The best-established treatment of idiopathic nightmare disorder is image rehearsal therapy, whereas systematic desensitization and progressive deep muscle relaxation training are suggested. There is lower-grade evidence for using lucid dreaming therapy and self-exposure therapy. Prazosin is useful for treating posttraumatic stress disorder–associated nightmares, whereas clonidine’s benefit is less clear (61). Several drugs (trazodone, atypical antipsychotic medications, topiramate, low-dose cortisol, fluvoxamine, triazolam and nitrazepam, phenelzine, gabapentin, cyproheptadine, and tricyclic antidepressants) and behavioral therapies (relaxation, hypnosis, eye movement desensitization) lack documented efficacy in controlled trials (04).

Sleep paralysis should be considered a disorder only if it results in clinically significant distress, including bedtime anxiety or difficulty initiating sleep. Explanation and reassurance are usually sufficient to address the patient’s concerns. Sleep hygiene, instructions on various sleep hygiene techniques (eg, going to sleep and waking up at the same time each day, and no use of alcohol or caffeine before bedtime), and specific instructions (eg, avoiding sleeping in a supine or prone position) may serve as preventative measures. Cognitive behavioral therapy could be helpful (48). Tricyclic antidepressants and selective serotonin reuptake inhibitors are commonly used to treat sleep paralysis, often in the context of narcolepsy, but no adequately reported studies of pharmacologic interventions are available. The evidence of the effectiveness of sodium oxybate in treating sleep paralysis was mixed and based on lower-quality evidence (14).

In REM sleep behavior disorder, the primary management goal is to prevent sleep-related injuries to patients and their bed partners. The first step is to propose environmental modifications by controlling bedroom safety and avoiding drugs that may potentially cause or precipitate REM sleep behavior disorder, such as most classes of antidepressants (50). The AASM suggests that clinicians use clonazepam or immediate-release melatonin to treat isolated or secondary REM sleep behavior disorder due to medical conditions in adults (27). Clonazepam and melatonin are clinically assumed to majorly modify or eliminate REM sleep behavior disorder in nearly all patients, although there is an urgent need to test the magnitude of this treatment effect. Finally, pharmacological treatment with clonazepam must always be personalized according to the type of patient, the risk of addiction, and the concomitant presence of respiratory disorders (43).

The AASM suggests that clinicians use transdermal rivastigmine for treating isolated REM sleep behavior disorder in adults with mild cognitive impairment and for the treatment of secondary REM sleep behavior disorder due to medical condition (Parkinson disease) and not use deep brain stimulation for the treatment of secondary REM sleep behavior disorder due to medical condition in adults (27).

In a single-center, randomized, double-blind placebo-controlled crossover trial in a selected population of 18 patients with Parkinson disease and REM sleep behavior disorder, 50 mg of 5-HTP daily improved sleep stability and contributed to ameliorating patients' global sleep quality (35).

Currently, no treatment is available that can modify the disease course of REM sleep behavior disorder or, at least, slow down the neurodegenerative process underlying phenoconversion (42).

Patients with other underlying sleep disorders, such as obstructive sleep apnea or periodic limb movements, should have these disorders appropriately treated to decrease the potential for sleep disruption (27).

References

01: American Academy of Sleep Medicine. International classification of sleep disorders: 3rd ed text revision. Darien, Illinois: American Academy of Sleep Medicine, 2023.
02: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Washington, DC: American Psychiatric Association, 2013.
03: Antelmi E, Pizza F, Franceschini C, Ferri R, Plazzi G. REM sleep behavior disorder in narcolepsy: A secondary form or an intrinsic feature? Sleep Med Rev 2020;50:101254. PMID 31931470
04: Arnulf I. Nightmares and dream disturbances. In: Principles and practice of sleep medicine, sixth edition. Kryger MH, Roth T, eds. Philadelphia: Elsevier Inc., 2017:1002-10.
05: Baldelli L, Pirazzini C, Sambati L, et al. Epigenetic clocks suggest accelerated aging in patients with isolated REM sleep behavior disorder. NPJ Parkinsons Dis 2023;9(1):48. PMID 36997543
06: Baldelli L, Provini F. Differentiating oneiric stupor in agrypnia excitata from dreaming disorders. Front Neurol 2020;11:565694.** PMID 33281702
07: Barone DA. Secondary RBD: not just neurodegeneration. Sleep Med Rev 2024;76:101938.** PMID 38657360
08: Bjorvatn B, Magerøy N, Moen BE, Pallesen S, Waage S. Parasomnias are more frequent in shift workers than in day workers. Chronobiol Int 2015;32(10):1352-8. PMID 26540469
09: Cesari M, Heidbreder A, St Louis EK, et al. Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group. Sleep 2022;45(3):zsab257. PMID 34694408
10: Choudhury P, Lee-Iannotti JK, Busicescu AO, et al. Validation of the RBD symptom severity scale in the North American Prodromal Synucleinopathy Consortium. Neurology 2024;102(3):e208008. PMID 38181331
11: Churchill L, Chen YC, Lewis SJG, Matar E. Understanding REM sleep behavior disorder through functional MRI: a systematic review. Mov Disord 2024;39(10):1679-96. PMID 38934216
12: Cicero CE, Giuliano L, Luna J, Zappia M, Preux PM, Nicoletti A. Prevalence of idiopathic REM behavior disorder: a systematic review and meta-analysis. Sleep 2021;44(6):zsaa294. PMID 33388771
13: Delage JP, Côté J, Journault WG, Lemyre A, Bastien CH. The relationships between insomnia, nightmares, and dreams: a systematic review. Sleep Med Rev 2024;75:101931.** PMID 38733767
14: Denis D, French CC, Gregory AM. A systematic review of variables associated with sleep paralysis. Sleep Med Rev 2018;38:141-57. PMID 28735779
15: Di Folco C, Couronné R, Arnulf I, et al. Charting disease trajectories from isolated REM sleep behavior disorder to Parkinson's disease. Mov Disord 2024;39(1):64-75. PMID 38006282
16: Elliott JE, Ligman BR, Bryant-Ekstrand MD, et al. Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium. Sleep 2024;47(6):zsae007. PMID 38181205
17: Fantini ML, Figorilli M, Arnulf I, et al. Sleep and REM sleep behaviour disorder in Parkinson's disease with impulse control disorder. J Neurol Neurosurg Psychiatry 2018;89(3):305-10. PMID 29066517
18: Fasiello E, Scarpelli S, Gorgoni M, Alfonsi V, De Gennaro L. Dreaming in parasomnias: REM sleep behavior disorder as a model. J Clin Med 2022;11(21):6379. PMID 36362607
19: Fernandez-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J. The clinical phenotype of idiopathic rapid eye movement sleep behavior disorder at presentation: a study in 203 consecutive patients. Sleep 2016;39(1):121-32. PMID 26940460
20: Figorilli M, Meloni F, Lecca R, et al. Severity of REM sleep without atonia correlates with measures of cognitive impairment and depressive symptoms in REM sleep behavior disorder. J Sleep Res 2023;32(5):e13880. PMID 36998161
21: Garriques VR, Dhruve DM, Nadorff MR. Nightmare disorder. Sleep Med Clin 2024;19(1):111-9. PMID 38368059
22: Geoffroy PA, Stern E, Maruani J, et al. The nightmare severity index (NSI): a short new multidimensional tool for assessing nightmares. J Sleep Res 2024;33(3):e14065. PMID 37846776
23: Haba-Rubio J, Frauscher B, Marques-Vidal P, et al. Prevalence and determinants of REM Sleep Behavior Disorder in the general population. Sleep 2018;41(2):zsx197. PMID 29216391
24: Hedman C, Pohjasvaara T, Tolonen U, Salmivaara A, Myllyla V. Parasomnias decline during pregnancy. Acta Neurol Scand 2002;105(3):209-14. PMID 11886366
25: Hogl B, Arnulf I, Bergmann M, et al. Rapid eye movement sleep behaviour disorder: past, present, and future. J Sleep Res 2022;31(4):e13612. PMID 35470494
26: Holtbernd F, Hohenfeld C, Oertel WH, et al. The functional brain connectome in isolated rapid eye movement sleep behavior disorder and Parkinson's disease. Sleep Med 2024;117:184-91. PMID 38555837
27: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med 2023;19(4):769-810. PMID 36515150
28: Iranzo A, Ramos LA, Novo S. The isolated form of rapid eye movement sleep behavior disorder: the upcoming challenges. Sleep Med Clin 2021;16(2):335-48. PMID 33985658
29: Joza S, Hu MT, Jung KY, et al. Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicenter study. Brain 2023;146(8):3258-72. PMID 36881989
30: Krohn L, Heilbron K, Blauwendraat C, et al. Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects. Nat Commun 2022;13(1):7496. PMID 36470867
31: Lee SY, Kim SJ, Kim HJ, Lee SA. Obstructive sleep apnea may reduce a diagnostic accuracy of video-polysomnography for idiopathic REM sleep behavior disorder. Sleep Med 2023;101:316-21. PMID 36470167
32: Liu J, Shuai G, Fang W, et al. Altered regional homogeneity and connectivity in cerebellum and visual-motor relevant cortex in Parkinson's disease with rapid eye movement sleep behavior disorder. Sleep Med 2021;82:125-33. PMID 33915428
33: Ma JF, Qiao Y, Gao X, et al. A community-based study of risk factors for probable rapid eye movement sleep behavior disorder. Sleep Med 2017;30:71-6. PMID 28215267
34: Matar E, McCarter SJ, St Louis EK, Lewis SJG. Current concepts and controversies in the management of REM sleep behavior disorder. Neurotherapeutics 2021;18(1):107-23. PMID 33410105
35: Meloni M, Figorilli M, Carta M, et al. Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson's disease. Sleep Breath 2022;26(3):1023-31. PMID 34403081
36: Miglis MG, Adler CH, Antelmi E, et al. Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. Lancet Neurol 2021;20(8):671-84.** PMID 34302789
37: Mondello S, Kobeissy F, Mechref Y, et al. Novel biomarker signatures for idiopathic REM sleep behavior disorder: a proteomic and system biology approach. Neurology 2018;91(18):e1710-5. PMID 30258025
38: Montini A, Loddo G, Baldelli L, et al. Sleep-related hypermotor epilepsy vs disorders of arousal in adults: a step-wise approach to diagnosis. Chest 2021;160(1):319-29. PMID 33529771
39: Mufti K, Rudakou U, Yu E, et al. Comprehensive analysis of familial parkinsonism genes in rapid-eye-movement sleep behavior disorder. Mov Disord 2021;36(1):235-40. PMID 33001463
40: Pagano G, De Micco R, Yousaf T, Wilson H, Chandra A, Politis M. REM behavior disorder predicts motor progression and cognitive decline in Parkinson disease. Neurology 2018;91(10):e894-e905. PMID 30089615
41: Perciaccante A, Coralli A. Franz Kafka’s insomnia and parasomnias. Lancet Neurol 2016;15(10):1014. PMID 27571153
42: Postuma RB. Neuroprotective trials in REM sleep behavior disorder: the way forward becomes clearer. Neurology 2022;99(7 Suppl 1):19-25. PMID 35970587
43: Raggi A, Mogavero MP, DelRosso LM, Ferri R. Clonazepam for the management of sleep disorders. Neurol Sci 2023;44(1):115-28. PMID 36112279
44: Schenck C, Bundlie S, Ettinger M, Mahowald MW. Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 1986;9(2):293-308. PMID 3505730
45: Schenck CH, Mahowald MW, Kim SW, et al. Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep 1992;15(3):226-35. PMID 1621023
46: Schredl M. Editorial for "Nightmares in narcolepsy--under-investigated symptom?" (SLEEP-D-13-00591) Understanding and treating nightmares in patients with narcolepsy. Sleep Med 2014;15(8):851-2. PMID 24958245
47: Sharpless BA, Barber JP. Lifetime prevalence rates of sleep paralysis: a systematic review. Sleep Med Rev 2011;15(5):311-5. PMID 21571556
48: Sharpless BA. A clinician’s guide to recurrent isolated sleep paralysis. Neuropsychiatr Dis Treat 2016;12:1761-7. PMID 27486325
49: Siclari F, Valli K, Arnulf I. Dreams and nightmares in healthy adults and in patients with sleep and neurological disorders. Lancet Neurol 2020;19(10):849-59. PMID 32949545
50: Sodre ME, Wiebner I, Irfan M, Schenck CH, Mota-Rolim SA. Awake or sleeping? Maybe both… A review of sleep-related dissociative states. J Clin Med 2023;12(12):3876. PMID 37373570
51: Stefani A, Heidbreder A, Brandauer E, et al. Screening for idiopathic REM sleep behavior disorder: usefulness of actigraphy. Sleep 2018;41(6):zsy053. PMID 29554362
52: Stefani A, Holzknecht E, Högl B. Clinical neurophysiology of REM parasomnias. Handb Clin Neurol 2019;161:381-96. PMID 31307615
53: Stefani A, Trenkwalder C, Arnulf I, et al. Isolated rapid eye movement sleep behaviour disorder: clinical and research implications. J Neurol Neurosurg Psychiatry 2023;94(7):581-2. PMID 36977554
54: Terzaghi M, Pilati L, Ghiotto N, et al. Twenty-four-hour blood pressure profile in idiopathic REM sleep behavior disorder. Sleep 2022;45(2):zsab239. PMID 34555174
55: Tsukita K, Sakamaki-Tsukita H, Tachibana N, Takahashi R. Polygenic burden of Parkinson's disease risk stratifies the prognosis of isolated rapid-eye-movement disorder: a preliminary observational study. Parkinsonism Relat Disord 2022;96:52-6. PMID 35217383
56: Valencia Garcia S, Libourel PA, Lazarus M, Grassi D, Luppi PH, Fort P. Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder. Brain 2017;140(2):414-28. PMID 28007991
57: Valli M, Uribe C, Mihaescu A, Strafella AP. Neuroimaging of rapid eye movement sleep behavior disorder and its relation to Parkinson's disease. J Neurosci Res 2022;100(10):1815-33. PMID 35790021
58: Wang C, Chen F, Li Y, Liu J. Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2022;93(4):395-403. PMID 34937751
59: Ye G, Xu X, Zhou L, Zhao A, Zhu L, Liu J. Evolution patterns of probable REM sleep behavior disorder predicts Parkinson's disease progression. NPJ Parkinsons Dis 2022;8(1):36. PMID 35383198
60: Zhang H, Gu Z, Yao C, et al. Risk factors for possible REM sleep behavior disorders: a community-based study in Beijing. Neurology 2020a;95(16):e2214-24. PMID 32788245
61: Zhang Y, Ren R, Sanford LD, et al. The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis. Sleep Med 2020b;67:225-31. PMID 31972510

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Federica Provini MD

Dr. Provini of the University of Bologna and IRCCS Institute of Neurological Sciences of Bologna received speakers' fees from Idorsia, Italfarmaco, and NeoPharmed Gentili Spa.
See Profile
Luca Baldelli MD

Dr. Baldelli of the University of Bologna has no relevant financial relationships to disclose.
See Profile

Editor

Antonio Culebras MD FAAN FAHA FAASM

Dr. Culebras of SUNY Upstate Medical University at Syracuse has no relevant financial relationships to disclose.
See Profile

Former Authors

Michael S Aldrich MD
Bradley V Vaughn MD

Patient Profile

Age range of presentation: REM sleep behavior disorders: 45-64 years; 65+ years

Recurrent isolated sleep paralysis: 13 to 18 years

Nightmare disorder: all ages
Sex preponderance: REM sleep behavior disorder: male > female

Recurrent isolated sleep paralysis: female = male

Nightmare disorder: female = male
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: Nightmares are a well-known symptom of posttraumatic stress disorder patients who are more at risk within 3 months of a trauma and sometimes persisting throughout life.

ICD & OMIM codes

ICD-10: Nightmares: F51.5

REM sleep behavior disorder: G47.52

Recurrent isolated sleep paralysis: G47: 53
ICD-11: Parasomnias related to REM sleep: 7B01

Recurrent isolated sleep paralysis: 7B01.1

Nightmare disorder: 7B01.2

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

REM sleep-related parasomnias

Associated Disorders

Obstructive sleep apnea syndrome
Restless legs syndrome
Periodic limb movements during sleep

Differential Diagnosis

Nocturnal frontal lobe epilepsy (sleep-related hypermotor epilepsy)
Conditions associated with nocturnal pain
Nocturnal movements or behaviors occurring during episodes of wakefulness
Epileptic seizures
Panic attacks

Also Relevant

Confusional arousal
Nightmares
Parasomnia overlap disorder and status dissociatus
Rapid eye movement sleep behavior disorder
Sleep and cerebral degenerative disorders
- Sleep and mental disorders
- Sleep and parkinsonism
- Sleep disorders
- Sleep paralysis
- Sleeptalking

Clinical Categories

Sleep Disorders

REM sleep-related parasomnias …

REM sleep-related parasomnias

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Table 1. Differences Between REM Sleep Parasomnias Features

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Telehealth and cognitive behavioral therapy for insomnia (CBT-I)

NonREM parasomnias

Neurologic disorders associated with obesity

Hypersomnolence

Sleep disorders in women

Sleep, stroke, and vascular dementia

Parasomnia overlap disorder and status dissociatus

Stimulant-dependent sleep disorder

REM sleep-related parasomnias

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Table 1. Differences Between REM Sleep Parasomnias Features

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Telehealth and cognitive behavioral therapy for insomnia (CBT-I)

NonREM parasomnias

Neurologic disorders associated with obesity

Hypersomnolence

Sleep disorders in women

Sleep, stroke, and vascular dementia

Parasomnia overlap disorder and status dissociatus

Stimulant-dependent sleep disorder

This is an article preview.
Start a Free Account
to access the full version.