Psychiatric Annals

CME 

Parasomnias: An Update

Michael J. Howell, MD; Imran S. Khawaja, MD; Carlos H. Schenck, MD

Abstract

Parasomnias comprise a category of sleep disorders that includes behavioral and emotional disturbances occurring during any stage of sleep or during states of mixed sleep and wakefulness. These disorders can range from having vocalizations and minor movements to very complex and aggressive behaviors that result in serious injury and disruption of sleep for the patients and the bed partners. Parasomnias need careful clinical history-taking often followed by a sleep lab study to rule out other sleep disorders. Parasomnias can frequently be mistaken as nocturnal manifestations of psychiatric disorders, which makes it very important for psychiatrists to have a proper understanding of these sleep disorders. [Psychiatr Ann. 2015;45(1):30–34.]

Abstract

Parasomnias comprise a category of sleep disorders that includes behavioral and emotional disturbances occurring during any stage of sleep or during states of mixed sleep and wakefulness. These disorders can range from having vocalizations and minor movements to very complex and aggressive behaviors that result in serious injury and disruption of sleep for the patients and the bed partners. Parasomnias need careful clinical history-taking often followed by a sleep lab study to rule out other sleep disorders. Parasomnias can frequently be mistaken as nocturnal manifestations of psychiatric disorders, which makes it very important for psychiatrists to have a proper understanding of these sleep disorders. [Psychiatr Ann. 2015;45(1):30–34.]

Parasomnias are abnormal behaviors that arise from, or occur while entering, sleep. They are classified as either nonrapid eye movement (NREM) or rapid eye movement (REM) parasomnias depending upon their associated state of sleep. Parasomnias are distinguished in numerous ways, including their timing during the sleep period, degree of amnesia, associations with other conditions such as restless legs syndrome (RLS) or obstructive sleep apnea (OSA), and by their particular behaviors (walking, eating, thrashing, punching, kicking). The majority of episodes are benign; however, sleep-related injury can occur to either the patient or bed partner, and a parasomnia may indicate underlying central nervous system (CNS) disease.1,2

NREM parasomnias are also referred to as disorders of arousal and include confusional arousals (CA), sleepwalking (SW), sleep-related eating disorder (SRED; sleepwalking plus eating), and sleep terrors. They arise when the cortex incompletely awakens from deep NREM sleep, often due to comorbid conditions that promote sleep inertia or provoke repeated arousal. SW and SRED can be induced when patients with RLS are treated with sedative hypnotic medications.3

REM sleep behavior disorder (RBD) is the most clinically relevant REM parasomnia and is characterized by the loss of normal REM muscle atonia, leading to dream-enactment behaviors. The loss of atonia in RBD is due to dysfunction of pontine neurons and frequently predicts the impending onset of neurodegenerative disease, Parkinson’s disease in particular, or another disorder of alpha-synuclein pathology.4

Nrem Parasomnias (Disorders of Arousal)

Clinical Presentation of NREM Parasomnias

Confusional Arousals

Disoriented amnestic behaviors after an arousal from deep NREM sleep (stage N3) are CAs. Vocalizations are common, and the CAs typically last fewer than 5 minutes and occur in approximately 4% of the adult population.1

Sleepwalking and Sleep-related Eating Disorder

SW is the combination of ambulation with impaired consciousness following an arousal from sleep. Patients have amnestic, inappropriate behaviors such as placing car keys in the refrigerator or rearranging furniture to nonfunctional locations. When a patient eats during an episode it is referred to as SRED. Attempting to arouse a SW patient is often difficult and may paradoxically worsen the confusion and disorientation. These disorders are common, with 18% and 5% of adults describing a history of SW or SRED, respectively. The majority of adults with SW claim that the behaviors began in childhood.1

Episodes of SW or SRED can be prolonged and/or dangerous, especially in the setting of sedative medications. Reports have described SW individuals cooking, leaving the house, driving an automobile, and sometimes discharging loaded firearms. These extended amnestic ambulating behaviors most commonly occur after patients with RLS are mistakenly treated with benzodiazepine receptor agonists. SRED can result in weight gain and dental carries as patients do not typically brush their teeth prior to returning to sleep.5

Sleep Terrors

Sleep terrors (ST) are nocturnal episodes of a distressed, often screaming, and inconsolable child with increased autonomic nervous system activity (increased heart rate and blood pressure). STs can last for more than 5 minutes, and attempts by parents to intervene results in a paradoxical increase in agitation. These behaviors often cause severe distress among family members, but the patient does not typically experience any daytime consequences. STs are quite common, with up to 25% of children younger than age 5 years having experienced at least one episode.1

Etiology of NREM Parasomnias

Disorders of arousal occur when there is an incomplete transition from NREM sleep into wakefulness. Processes that lead to NREM parasomnias include both (1) phenomena that deepen sleep, thus impeding normal arousal mechanisms (sleep deprivation, sedative medications); and (2) conditions that cause repeated arousals (eg, OSA, noise), leading to sleep fragmentation. The activation of motor circuits with a relative paucity of activity in brain regions that control executive function and memory account for the poor judgment and amnesia that characterize these disorders.5

Patients with RLS are predisposed to NREM parasomnias with ambulation (SW and SRED), especially when treated with the commonly prescribed benzodiazepine receptor agonists. This happens when RLS patients are erroneously diagnosed with a hypervigilant insomnia such as psychophysiological insomnia. This mistake is an easy one to make, as patients with RLS frequently present to medical attention with a primary complaint of sleep initiation difficulty and only ambiguous allusions to motor symptoms. Of note, the majority of patients with RLS, unlike those with psychophysiological insomnia, describe wakeful nocturnal eating as part of their syndrome. This “restless eating” is similar to the classic motor symptoms of RLS, in which patients describe an urge to eat that must be addressed in order to fall asleep. Thus, once a patient with RLS is misdiagnosed with psychophysiological insomnia and subsequently treated with a benzodiazepine receptor agonist (an agent that suppresses hippocampal and executive function), amnestic predisposed behaviors are unleashed, which in the case of RLS include ambulation (SW) and eating (SRED).3,5

Several cases of psychotropic medications inducing NREM parasomnias have been reported.6 Not unexpectedly, there has been an increase in SW and SRED reports in parallel with the contemporary rise in use of sedative hypnotic medication.3

Management of NREM Parasomnias

Most NREM parasomnias are benign and patients just need reassurance and advice to avoid sleep deprivation and sedating medications. Situations that deserve more thorough investigation include violent/potentially injurious behaviors, or if they are associated with symptoms suggestive of another sleep disorder. Bed partner reports are particularly helpful, as most patients are unable to properly recall the nocturnal events by the time they are discussed with a clinician.3

In-laboratory video polysomnography (PSG) can be helpful even if abnormal behaviors do not arise during the sleep study because PSG can identify reversible comorbid conditions such as OSA and rule out REM sleep without atonia (see RBD management below).

When SW or SRED have been induced by a sedative-hypnotic agent, it is of critical importance to reconsider the diagnosis for which the medication was originally prescribed. In particular, careful scrutiny for RLS is warranted as the difficulty with sleep initiation of RLS is frequently mistakenly for other forms of insomnia. Further, many of these patients are on commonly prescribed pharmaceutical agents that mask RLS symptoms. These agents include benzodiazepines, opiods, gabapentin, pregabalin, and sedating antidepressants. Discontinuing the offending agent and treating the underlying RLS will typically resolve the SW disorder.3,4

Environmental safety is important. Patients should be advised to remove any firearms from the bedroom, and windows should be closed and, if necessary, locked. Door alarms can signal other family members that a sleepwalker is wandering; however, loud auditory stimuli can paradoxically worsen NREM parasomnias.1,3

If disorders of arousal persist despite the resolution of comorbid sleep disorders and after the removal of inducing agents, pharmacological intervention may be considered. A variety of different therapies, typically benzodiazepines, have been reported as effective. However, at present, there is a paucity of clinical trial data.3 The most commonly reported pharmacological treatments for sleepwalking are intermediate- or long-acting benzodiazepines. The efficacy of these agents would be paradoxical (as noted above); other sedative hypnotics such as benzodiazepine receptor agonists frequently induce amnestic nocturnal behavior. The most extensively reported benzodiazepine for the treatment of disorders of arousal is clonazepam. One series reported a satisfactory treatment in 74% of patients.7 Conversely, another investigation reported that all clonazepam-treated patients discontinued therapy within 1 year with a persistence of SW.8 Antidepressants may have some efficacy in the treatment of ST, whereas these agents have been reported to exacerbate SW.3 Clearly, more clinical trials are necessary to provide stronger evidence-based recommendations to patients with NREM parasomnias.

REM Parasomnias

Clinical Presentation of REM Parasomnias

REM Sleep Behavior Disorder

Under normal physiological conditions, the activated mental state of REM sleep is combined with skeletal muscle paralysis, preventing dream enactment behavior (DEB). In RBD, this normal REM atonia is lost and DEB emerges. The activity varies from small hand movements to injurious activities such as trashing, punching, kicking, or diving out of bed.1

With a prevalence of 0.5%, it is estimated that 35 million individuals world-wide have RBD, with higher frequencies among the elderly, particularly those with neurodegenerative disease. Among younger adults (<40 years), RBD is most frequently reported in association with antidepressant medications or in the setting of narcolepsy.1,3,4

RBD occurs more often during the second half of the night. In addition to violent behaviors, patients may have loud, aggressive, and expletive-laden vocalizations discordant from waking personality. Patients and family members may deal with DEB for years prior to seeking medical attention.3

The majority of spontaneously developing RBD cases are related to alpha-synuclein brain pathology. Ultimately, the majority of surviving RBD patients progress to Parkinson’s disease (PD) or other similar disorder such as multiple system atrophy (MSA), or dementia with Lewy bodies (DLB).9

Patients with RBD demonstrate various subtle features of alpha-synuclein neurodegeneration. These include motor impairments (decreased hand dexterity, gait freezing), cognitive dysfunction (poor visual-constructional skills), anosmia, constipation, and autonomic dysfunction (orthostasis).4

Etiology of REM Sleep Behavior Disorder

Several diverse pathologies can lead to RBD, including alpha-synuclein neurodegeneration, orexin dysfunction, and a toxic effect from antidepressant medications. They all manifest in a loss of behavioral control during REM sleep and the enactment of dream mentation.4

The suppression of motor activity during REM sleep is the cumulative result of multiple pathways, including pontine REM-on (precoeruleus and sublateral dorsal) and REM-off (ventral lateral portion of the periaquaductal grey matter and lateral pontine tegmentum) nuclei that ultimately terminate upon spinal motor neurons.3

Alpha-Synuclein Neurodegeneration

The REM-on and REM-off nuclei are involved early in the natural history of PD and other similar disorders. The interval between the onset of RBD and the parkinsonian triad of resting tremor, bradykinesia, and cogwheel rigidity varies from months to decades.4 On average, approximately 50% of patients convert to a neurological disorder 10 years after the start of RBD symptoms.9,10 Functional neuroimaging studies reveal progressive dopaminergic abnormalities in RBD consistent with preclinical neuronal dysfunction.11

Orexin Dysfunction

Approximately half of narcolepsy patients also have RBD symptoms. Orexin, the deficient neurotransmitter, normally stabilizes sleep state (NREM, REM) and prevents frequent transitioning between sleep and wakefulness. When deficient, REM-wake instability arises with wake-like motor activity in parallel with REM dream mentation.12

Antidepressant Toxicity

Medications to treat depressed mood can acutely precipitate or exacerbate DEB. Implicated medication classes include tricyclic and tetracyclic antidepressants, monoamine oxidase inhibitors, serotonin-specific reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors.13

Medication-induced RBD may, in fact, be the most prevalent form of RBD, especially among younger people. It is possible that these medications do not cause a de novo induction of RBD, as these patients may have otherwise developed RBD later. A recent study demonstrated that patients with medication-induced RBD also have prodromal markers of PD, including anosmia, constipation, and subtle motor impairments. These findings provide evidence that antidepressants may not induce RBD but instead unmask it in individuals at risk of alpha-synuclein neurodegeneration.14

Management of REM Sleep Behavior Disorder

Recurrent, brief DEB occurring in the later half of the sleep period followed by complete alertness and orientation upon awakening are features that help to distinguish RBD from the NREM parasomnias. PSG is necessary for diagnosis and helpful in excluding other sleep disrupting conditions such as OSA, nocturnal seizures, and periodic limb movements. Even if abnormal behaviors do not arise during the sleep study, REM sleep without atonia can be identified, and when it is present in combination with a history of dream enactment it establishes a diagnosis of RBD.1

In cases of suspected RBD, a clinician should inquire about other ancillary PD symptoms such as tremor, gait impairment, and difficulty with bowel motility and smell. When chronic, otherwise unexplained anosmia and constipation coexist with RBD, they are highly suggestive of an impending neurodegenerative disorder.4,10

As in the case of NREM parasomnis, RBD management should initially focus upon optimizing bedroom safety. Subsequently, aggravating agents should be eliminated (if possible) and comorbid sleep disorders treated. Most cases of medication-induced RBD are self-limited following discontinuation of offending medication, and DEB typically improves if underlying OSA is treated.3,4

The most commonly prescribed medications for RBD include clonazepam and/or melatonin.3,4 However the use of these agents is largely based upon consensus, with only limited existing evidence from controlled clinical trials.15 As in NREM parasomnias, clonazepam has been the most widely prescribed agent for RBD, and approximately 90% of patients respond well to low doses (0.5–1.0 mg) at least initially.4,16 Although the majority of patients respond to clonazepam at first, long-term follow-up studies are mixed. The results range from sustained benefit without dose escalation to others with a high incidence of dose escalation and treatment failure.17 Clonazepam is particularly problematic in the setting of advanced neurodegenerative disease, where its prolonged duration of action may result in morning sedation as well as cognitive and gait impairment. Melatonin can be taken in high doses (6–15 mg), either in combination with clonazepam or as sole therapy.3 It is often chosen as first-line therapy among patients with neurodegenerative disease due to its limited side-effect profile compared with clonazepam.18 In cases of medically refractory RBD, a customized bed alarm that delivers a calming message at the onset of DEB may be helpful in preventing injury.19

Psychiatric Disorders Presenting as Parasomnias

Some mental health disorders may include symptoms that occur predominantly during the sleep period and must be differentiated from primary parasomnias. For example, panic attacks are well known to occur during sleep. Close to 70% of patients with panic disorder have had a sleep-related panic attack.20 Clinical features of nocturnal panic attacks are similar to daytime panic attacks and patients are aroused to rapidly achieve full wakefulness with typical panic anxiety and subsequent difficulty in resuming sleep. Most of these patients have a history of daytime panic attacks.

Sleep disturbances are prominent in patients with posttraumatic stress disorder (PTSD).21 Sleep complaints of patients with PTSD include fragmented sleep, increased awakenings, limb movements, nightmares, night terrors, and even purposeful behavior mimicking dream enactment.22 Nightmares occur both in REM and NREM sleep. Even though there are several reports suggesting motor activation in stage REM sleep, most studies show no significant polysomnographic findings suggestive of RBD in these patients. For this reason, sleep disturbances of PTSD are not included in the section of parasomnias in either the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)2 or in the International Classification of Sleep Disorders, third edition (ICSD-3).1

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Authors

Michael J. Howell, MD, is the Program Director, Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center; and an Assistant Professor of Neurology, Department of Neurology, University of Minnesota. Imran S. Khawaja, MD, is the Medical Director, Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center; and an Associate Professor in Neurology, University of Minnesota. Carlos H. Schenck, MD, is a Professor, Department of Psychiatry, University of Minnesota.

Address correspondence to Michael J. Howell, MD, Department of Neurology, 717 Delaware Street SE, MMC 295, Minneapolis, MN 55414; email: howel020@umn.edu.

Disclosure: Michael J. Howell has received consulting fees from Inspire Medical and has done contracted research for General Electric. The remaining authors have no relevant financial relationships to disclose.

10.3928/00485713-20150106-07

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