Our awareness of the complexity of sleep expanded in 1953 with the discovery of rapid-eye-movement (REM) sleep by Aserinsky and Kleitman. Sleep was no longer considered a homogenous state, but rather a dynamic process of cycling between two distinct states, non-REM and REM sleep. Under normal circumstances the boundaries between non-REM, REM and wakefulness are well declared. Dissociative sleep disorders involve a breakdown of these boundaries (Mahowald and Schenck 1992), and provide a unique window on the neurophysiological mechanisms responsible for each state. Narcolepsy, a disorder of the boundary between wakefulness and REM sleep, is probably the most studied disorder of this nature. The following is a review of another recently described REM sleep boundary disorder called REM sleep behavior disorder (RBD). RBD is characterized by the acting-out of violent dreams during REM sleep, often with injurious consequences (Schenck et al. 1986, 1987). As with narcolepsy, RBD involves a dissociation of REM sleep phenomena and their underlying mechanisms, therefore providing yet another opportunity to broaden our understanding of the complexity of sleep.
A brief discussion of REM sleep phenomenology is required before proceeding. REM sleep is characterized by specific phenomena that distinguish it from non-REM sleep and wakefulness (Siegel 1994). These phenomena are grouped according to whether their occurrence is tonic (occurring throughout REM) or phasic (occurring intermittently during REM). Tonic phenomena include, low-voltage desynchronized electroencephalogram (EEG), hippocampal theta rhythm, electromyographic (EMG) atonia, olfactory bulb activity, high arousal threshold, elevated brain temperature, poikilothermia, and penile tumescence. Phasic phenomena include, rapid eye movements, ponto-geniculo-occipital spikes, somatic muscle-limb twitches, middle ear activity, tongue movements, and variability in autonomic control of cardiac and respiratory functions. It remains unclear whether dreaming occurs tonically or phasically in REM sleep. The dissociation of the normal association between muscle atonia and REM sleep is a key component of the pathophysiology of RBD.
Despite the relatively recent systematic description of RBD (Schenck et al. 1986, 1987), enough case studies exist to draw some general conclusions. Patients usually seek medical attention with a complaint of vigorous sleep behaviors associated with repetitive vivid, violent and fearful dreams (i.e., being attacked by animals or people). Behaviors include talking, yelling, swearing, punching, kicking, jumping out of bed, crawling, running, etc. The bed-partner is often the recipient of this violent behavior. These sleep behaviors frequently result in injury to the patient and/or their bed-partner (i.e., ecchymoses, lacerations, and fractures, in one case resulting in admission to the intensive care unit (Schenck 1991)). The measures taken by patients to avoid injury best demonstrate the potential risk; patients may sleep in zipped up sleeping bags, on a mattress on the floor of an empty room, or tethered to the bed. Bed-partners may move to another bed or room, but many feel compelled to stay in the same room to protect the partner from injury. The violent nature of the dream-enacting behavior is usually discordant with the patient’s calm and friendly waking personality, suggesting that RBD is not only a disorder of motor control, but also a dream disorder. The observation that routine dreams are not acted out further supports this hypothesis.
The onset of dream-enactment usually occurs after at least the first 90 minutes of sleep, corresponding to the usual time for the first REM sleep period. The behaviors may occur as late as just before awakening in the morning, the time when REM sleep is most prevalent. Limb jerking usually occurs every night, but major episodes vary from as infrequent as once each two weeks to as frequent as four times nightly for 10 consecutive nights. RBD patients usually do not complain of sleep disruption secondary to dream- enactment, but may be awaken by their spouse’s yelling. Upon awakening, patients are alert and oriented with complete recollection of the dream they were enacting. The behaviors exhibited usually correlate well with the recalled dream. The following is a case history of a patient copied from Mahowald and Schenck (1994) that demonstrates the typical presentation of RBD:
Schenck et al. (1993) provide a comprehensive review of 96 patients diagnosed with RBD in their sleep laboratory. The vast majority (87.5%) of patients afflicted by RBD were older males (mean age at onset=52.4 years). However, females and children as young as 10 years were diagnosed with RBD. Approximately 25% of their RBD patients reported a lengthy prodrome involving sleep-talking, yelling, and excessive limb twitching and jerking during sleep, suggesting a progressive dysregulation of motor control during sleep. A few isolated cases gave histories suggestive of a familial predisposition. Schenck’s et al. (1993) review of the world literature on reported RBD cases failed to reveal any significant divergence from their 96 cases.
In the sleep laboratory, polysomnography reveals relatively normal sleep architecture. One frequently observed exception is an age specific elevation in slow-wave sleep (Schenck et al. 1993). The significance of this increase remains unexplained. Seizure activity is never recorded in association with episodes of RBD. With the onset of REM sleep there is often an abrupt increase in submental EMG activity, in contrast to the typical atonia associated with normal REM sleep. Consequently, standard sleep stage scoring guidelines (Rechtschaffen and Kales 1968) which require atonia for REM sleep to be scored must be modified (Lapierre and Montplaisir 1992). Limb twitching exceeding that of normal is usually observed (Lapierre and Montplaisir 1992). Outright dream enactments recorded in the sleep laboratory differ little from those reported by spouses with the exception that extreme episodes are unlikely to be observed during one or two nights in the laboratory. Dream reports elicited following sleep behavior never contradict the behaviors exhibited and usually show a close correlation. During non-REM sleep periodic and aperiodic limb movements are observed indicating that the motor dyscontrol is not exclusive to REM sleep. However, these movements do not approach the magnitude observed during REM sleep.
The American Sleep Disorders Association (ASDA) first officially recognized RBD as a sleep disorder in 1990. The ASDA’s International Classification of Sleep Disorders (ICSD 1990) states the following criteria for the diagnosis of RBD:
Minimum Criteria: B plus C.
Severity Criteria:
Mild: REM sleep behavior that occurs less than once per month; only mild discomfort for patient or bedpartner.
Moderate: REM sleep behavior that occurs more than once per month but less than once per week; usually associated with physical discomfort to the patient or bedpartner.
Severe: REM sleep behavior that occurs more than once per week; associated with physical injury to the patient or bedpartner.
RBD occurs in either an acute or chronic form. Acute RBD is usually associated with some form of toxicity with most cases involving acute withdrawal from ethanol (Tachibana 1975). RBD following withdrawal from nitrazepam (Atsumi 1977) and biperiden (Sugano 1980) can also occur. Loss of REM atonia has been linked to medications including tricyclic antidepressants (Shimizu 1985), monoamine oxidase inhibitors (Akindele 1970), and fluoxetine (Schenck 1992). Acute RBD has also been reported in intensive care unit patients following a stroke (Schenck 1991).
Approximately half of the chronic cases of RBD are considered idiopathic with the other half being associated with a variety of neurological disorders. These include vascular insult (i.e., subarachnoid hemorrhage (Schenck et al. 1986)), tumors (i.e., acoustic neuroma (Isono et al. 1979) and pontine neoplasm (De Barros-Ferreira et al. 1975)), and degenerative disorders; amyotropic lateral sclerosis (Minz 1979), anterior-dorsomedial thalamic syndrome (Lugaresi 1986), dementia (Schenck et al. 1986), demyelinating disorder (Schenck et al. 1986), olivopontocerebellar degeneration (Schenck et al. 1987), Parkinson’s disease (Schenck et al. 1996), progressive supranuclear palsy (Salve 1986), Shy-Drager syndrome (Wright et al. 1990), and narcolepsy (Schenck and Mahowald 1992). In summary, multiple neurological disorders have the potential of effecting the neural centers involved in REM sleep motor and dream control.
Recently, Schenck et al. (1996) reported the emergence of Parkinsonian disorder in men previously diagnosed with idiopathic RBD. Thirty-eight percent of 29 men developed Parkinsonian disorder at a mean interval of 3.7 years after being diagnosed with idiopathic RBD, and 12.7 years after the onset of RBD. Schenck et al. do not attribute the link between RBD and subsequent Parkinsonian disorder to the treatment of RBD with clonazepam. This finding suggests that RBD may be the first heralding sign of Parkinsonian disorder. There is also one report of Shy-Drager syndrome first presenting as RBD (Wright et al. 1990). Given the relatively recent systematic diagnosis of RBD, patients with RBD currently diagnosed as idiopathic may subsequently develop other neurological disorders. Furthermore, as postmortem brain analyses accumulate the underlying defects responsible for RBD may become more apparent.
The association between RBD and narcolepsy is of particular interest since both are dissociative disorders involving REM sleep (Mahowald and Schenck 1992). Narcolepsy is characterized by the intrusion of various REM features into wakefulness; cataplexy is the sudden intrusion of REM sleep muscle atonia into wakefulness, usually induced by extreme emotion; sleep paralysis is the persistence of REM atonia into wakefulness following arousal from REM sleep; sleep attacks usually involve the intrusion of REM sleep into wakefulness; and hypnagogic hallucinations are thought to represent dream mentation persisting into wakefulness. In patients with RBD and narcolepsy the disorders usually develop concurrently, suggesting a common or related cause. This is further supported by the finding that the incidence of the DQB1*0602 (DQwl group) allele of the human leukocyte antigen (HLA) class II gene is elevated in both narcoleptics and non-narcoleptic patients with RBD (Schenck et al. 1996). The additional finding that narcoleptics posses the DR2 haplotype, while RBD patients do not, may explain the different manifestations of the two dissociative disorders of REM sleep.
The exact underlying pathophysiology causing RBD remains elusive given the absence of overt neurological pathology in the idiopathic group and the diverse neuropathologies observed in the remaining patients. However, an experimental animal model that preceded the systematic description of RBD in humans provides insight into the mechanisms responsible for RBD. Cats with bilateral pontine tegmental lesions display tonic EMG activity and behaviors during REM sleep which strongly resemble those observed in humans with RBD (Hendricks et al. 1982). The degree and type of behavior exhibited depends upon the location and size of the lesion. The behavioral spectrum, from mildest to most extreme, include 1) excessive limb and truncal twitching, 2) orienting and exploratory behaviors, including head raising, head turning, staring, 3) stalking and attacking imaginary prey, and 4) all of the above with locomotion. As in humans, the behaviors are never appetitive (i.e., sexual or feeding).
Hendricks et al. propose that the variability in behavioral response to different lesions suggests the involvement of two systems in RBD. One system is thought to control REM sleep atonia, while the other suppresses phasic motor pattern generators during REM sleep. Lesions of the first system simply result in REM sleep without atonia; this lesion by itself is insufficient to cause actual release of behaviors during REM sleep. Lesion to the second system result in the elaborate behaviors mentioned above.
While the link between RBD and pontine lesions in cats is clear, pontine lesions are implicated in only a few cases of human RBD (i.e., olivopontocerebellar degeneration; Schenck et al. 1987). However, Schenck et al. (1996) propose that the link between Parkinsonian disorder and RBD may be a result of reciprocal connectivity between the substantia nigra, the main site of pathology in Parkinsonian disorder, and the pedunculopontine nucleus (PPN), a nucleus with significant connections to the REM sleep atonia circuitry (Lad and Seigel 1990; Garcia-Rill 1991) and the REM sleep phasic circuitry (Shouse and Seigel 1992). Neuronal loss in the PPN associated with Parkinsonian disorder lends support to this hypothesis (Jellinger 1991). The other neurological disorders associated with RBD are likely to have a similar mediating effect via these structures in the pons.
Treatment with clonazepam is highly effective in reducing the frequency and severity of symptoms in most cases of RBD (Mahowald and Schenck 1994). Incidentally, clonazepam is effective in treating naturally occurring RBD in domestic dogs and cats (Hendricks et al. 1989). Clonazepam appears to enact its therapeutic effect on the phasic circuitry of REM sleep since polysomnography reveals persistent dissociation of normal REM atonia while on clonazepam (Lapierre and Montplaisir 1992). The initial dose of 0.5 mg. at bedtime is rapidly titrated to l.0 mg. if symptoms persist. Discontinuation usually results in the rapid return of symptoms. Side-effects such as sleep onset insomnia, prominent limb jerking at sleep onset, and excessive morning sedation can be alleviated by taking clonazopam up to two hours before bedtime without compromising the therapeutic effect.
The following medications have been used in patients that fail to respond successfully to clonazepam; desipramine or imipramine (Schenck et al. 1986; Matsumoto et al. 1991); carbamazepine (Bamford 1993); and clonidine, carbidopa/L-dopa and L-tryptophan (Schenck and Mahowald 1990). The therapeutic effect of desipramine, imipramine and clonidine is thought to be mediated via REM sleep suppression. The mode of action of the other medications is unknown. The rare occurrence of relapses while on medications for RBD stresses the need to maintain a safe sleeping environment. This includes removal of potentially injurious objects from the bedroom, putting cushions around the bed, and protecting the windows.
In summary, RBD is a recently described dissociative disorder of REM sleep characterized by the enactment of violent dreams, often with injurious consequences, primarily affecting older men. Acute forms associated with withdrawal syndromes and chronic forms have been described. Chronic RBD is associated with a variety of neuropathologies in half the cases, with the other half being idiopathic. Apparent idiopathic RBD may be the heralding sign of Parkinsonian disorder, and possibly other disorders. The proper diagnosis of RBD is critical given the potential risk of injury to the patient and their bed-partner, and the availability of remarkably effective treatment with clonazepam. Finally, the investigation of experimentally induced RBD in animals and naturally occurring RBD in humans provides a unique window on the mechanisms underlying the complex process of sleep.
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A 60-year-old surgeon began to punch and kick his wife and jump out
of bed during nightmares of being attacked "by criminals, terrorists,
and monsters who always tried to kill me." Work-related stress was the
presumed the cause of his sleep disturbance, but the violent behaviors
intensified despite retirement 3 years later. He sustained several head
lacerations, and his wife once had a severe headache for 2 days after
receiving an accidental blow to the ear. The proper diagnosis was
established after 11 years. A prodrome of excessive limb and body
jerking during sleep had been present for at least 33 years.
Diagnostic Criteria:
A. A complaint of violent or injurious behavior during sleep.
B. Limb or body movement associated with dream mentation.
C. At least one of the following:
1. Harmful or potentially harmful sleep behaviors;
2. Dreams appear to be "acted out";
3. Sleep behaviors disrupt sleep continuity.
D. Polysomnographic monitoring demonstrates at least one of the following
electrophysiological measures during REM sleep:
1. Excessive augmentation of chin EMG tone;
2. Excessive chin or limb phasic EMG twitching, irrespective of chin
EMG activity; and one or more of the following clinical features
during REM sleep;
3. Excessive limb or body jerking;
4. Complex, vigorous, or violent behaviors;
5. Absence of epileptic activity in association with the disorder.
E. Not associated with psychiatric disorders, but may be associated with
neurological disorders.
F. Other sleep disorders can be present, but are not the cause of the
behavior, e.g., sleep terrors, sleepwalking.
The differential diagnosis of RBD includes sleep-related seizures, confusional arousals, sleep walking, sleep terrors, post-traumatic stress syndrome, and nightmares (ICSD 1990). The characteristic polysomnographic findings outlined above are usually sufficient to rule out each of these disorders. To effectively rule out seizure activity the polysomnographic evaluation must include a complete International 10-20 BEG montage. A clinical history without polysomnography and a 10-20 EEG montage is insufficient to make a diagnosis.