Chapter 94 Non-REM Arousal Parasomnias
Parasomnias are defined as unpleasant or undesirable behavioral or experiential phenomena that occur predominantly or exclusively during the sleep period. These were initially thought to represent a unitary phenomenon, often attributed to psychiatric disease. As more parasomnias are being carefully studied both polygraphically and clinically, it is becoming apparent that parasomnias are not a unitary phenomenon, but rather are due to a large number of completely different conditions, most of which are diagnosable and treatable. Moreover, most, in fact, are not the manifestation of psychiatric disorders and are far more prevalent than previously suspected. The parasomnias may be conveniently categorized as primary parasomnias (disorders of the sleep states per se), and secondary parasomnias (disorders of other organ systems manifest themselves during sleep). The primary sleep parasomnias can be classified according to the sleep state of origin: rapid eye movement (REM) sleep, non-REM (NREM) sleep, or miscellaneous (i.e., those not respecting sleep state). The secondary sleep parasomnias can be further classified by the organ system involved1 (see Box 96-1).
The focus of this chapter is on the NREM sleep arousal parasomnias, which occur on a broad spectrum and include confusional arousals, sleepwalking, and sleep terrors. The underlying pathophysiology is state dissociation—the brain is partially awake and partially in NREM sleep. The result of this mixed state of being is that the brain is awake enough to perform very complex, and often protracted motor or verbal functions, but it is asleep enough not to have conscious awareness of or responsibility for these actions. These NREM parasomnias are not usually due to underlying serious psychological or psychiatric conditions, and more importantly, they are diagnosable and usually readily treatable.
There is compelling evidence that extensive reorganization of central nervous system activity occurs as the brain cycles through the three primary states of being: wakefulness, non–rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. The concept that certain parts of the nervous system are active in one state but not in the other two is erroneous. Almost all portions of the nervous system are active across all three states of being, but active in a different mode. The reticular response reversal phenomenon, in which excitation of the same anatomic site can have opposite effects on motor activity, depending upon the state (wake or REM) during stimulation is testimony to that fact.2,3
Relevant to many of the parasomnias occurring in humans is the demonstration that the effects of cholinergic drug injection into the pontine reticular formation of cats may have dramatically different effects, depending upon the state of the animal at the time of injection: If the drug is administered during NREM sleep, a state identical to naturally occurring REM sleep is induced; if it is administered during wakefulness, a waking-dissociated state occurs, characterized by EEG desynchronization and muscle atonia in a cat that appeared to be awake and able to track objects in its visual field.4 The concept that wake and sleep are all-or-none and therefore mutually exclusive states is erroneous. Sleep is not a global or whole-brain phenomenon.5 Such a waking-dissociated state is likely the basis for many human parasomnias, both REM and NREM parasomnias. A intracerebral neurophysiologic study in a patient with a NREM parasomnia supports this concept.6
Parasomnias are clinical phenomena that appear as the brain becomes reorganized across states; therefore, they are particularly apt to occur during the transition periods from one state to another. In view of the large number of neural networks, neurotransmitters, and other state-determining substances that must be recruited synchronously for full state declaration and the frequent transitions among states during the wake–sleep cycle, it is surprising that errors in state declaration do not occur more often than they do.7–9
The concept that sleep and wakefulness are not invariably mutually exclusive states and that the various state-determining variables of wakefulness, NREM sleep, and REM sleep can occur simultaneously or oscillate rapidly is key to the understanding the primary sleep parasomnias. The mixture of wakefulness and NREM sleep would explain confusional arousals (sleep drunkenness), automatic behavior, or microsleeps.9 The tonic and phasic components of REM sleep can become dissociated, intruding or persisting into wakefulness, explaining cataplexy, wakeful dreaming, lucid dreaming, and the persistence of motor activity during REM sleep (REM sleep behavior disorder [RBD]).10
The disorders of arousal are the most impressive and most common of the NREM sleep parasomnias. These share common features: They tend to arise from slow-wave sleep (stages 3 and 4 of NREM sleep), therefore usually occurring in the first third of the sleep cycle (and rarely during naps), and they are common in childhood, usually decreasing in frequency with increasing age.11,12 There is often a family history of disorders of arousal; however, this association has recently been questioned.13 A specific HLA gene (DQB1) appears to confer susceptibility to sleepwalking.14 Importantly, although they most commonly occur during stage N3 sleep (stages 3 and 4 of NREM sleep or slow-wave sleep), disorders of arousal can occur during any stage of NREM sleep, and they can occur late in the sleep period.15
Disorders of arousal may be associated with febrile illness, prior sleep deprivation, physical activity, or emotional stress.16–18 Contrary to popular opinion, alcohol appears not to play a role in triggering disorders of arousal.19 Medication-induced cases have been reported with sedative-hypnotics, neuroleptics, minor tranquilizers, stimulants, and antihistamines, often in combination with each other.17,20–24 There have been numerous reports of extremely complex activities attributed to sedative-hypnotic agents, often resulting in forensic issues. This issue is thoroughly discussed in Chapter 63. In some women, disorders of arousal be exacerbated by pregnancy or menstruation, whereas in others, disorders of arousal may be alleviated by pregnancy, suggesting hormonal influences.25–27 Such precipitants should be thought of as triggering events in susceptible persons, and not causing them. Underlying predisposing, priming, and precipitating factors have been thoroughly reviewed elsewhere.18
Numerous other sleep disorders that result in arousals (obstructive sleep apnea,28 nocturnal seizures, or periodic limb movements) can provoke these disorders. Sleep-disordered breathing has been found to be more prevalent in children and adults with disorders of arousal. One study found that sleep fragmentation induced by sleep-disordered breathing is more common in adults with disorders of arousal than in normal subjects.29,30 The combination of frequent arousals and sleep deprivation seen in these other sleep disorders provide fertile ground for the appearance of disorders of arousal. These represent a sleep disorder within a sleep disorder—the clinical event is a disorder of arousal, but the true culprit is a different, unrelated sleep disorder. This would explain the common clinical experience of improvement of disorders of arousal following identification and treatment of obstructive sleep apnea.31 Conversely, effective treatment of obstructive sleep apnea with nasal CPAP can result in disorders of arousal, presumably associated with deep NREM sleep rebound.32,33
Persistence of these activities beyond childhood or their development in adulthood is often taken as an indication of significant psychopathology.34,35 Numerous studies have dispelled this myth, indicating that significant psychopathology is usually not present in adults with disorders of arousal.36–38 In one study in children, there was an association between disorders of arousal and anxiety.39 These arousals might not be the culmination of ongoing psychologically significant mentation, in that somnambulism can be induced in normal children by standing them up during slow-wave sleep,40,41 and sleep terrors can be precipitously triggered in susceptible persons by sounding a buzzer during slow-wave sleep.11,42
The mechanism of these disorders is not clear, but clearly both genetic43 and environmental factors are operant. It has been suggested that sleep terrors may be the manifestation of anomalous REM sleep mixed with NREM sleep.44
In addition to the phenomenon of state dissociation, in which two states of being overlap or occur simultaneously, there are likely additional underlying physiologic phenomena that contribute to the appearance of complex motor actions during sleep. These include locomotor centers, sleep inertia, and sleep state instability.
Locomotor centers, present in multiple sites in the central nervous system, may play a role in the disorders of arousal, which represent motor activity that is dissociated from waking consciousness.45 These areas project to the central pattern generator of the spinal cord, which itself is able to produce complex stepping movements in the absence of supraspinal influence.46 This accounts for the fact that decorticate experimental and barnyard animals are capable of performing very complex, integrated motor acts.47 A biological substrate is further supported by the similarity between spontaneously occurring sleep terrors in humans and sham rage induced in animals.48–50 Indeed, human neuropathology can result in similar activities.51–55 Dissociation of the locomotor centers from the parent state of NREM sleep would explain the presence of complex motor behavior seen in disorders of arousal. Spontaneous locomotion following decerebration in cats clearly indicates that such centers, if dysfunctional, release motor activity into the sleeping state.56,57 Single proton emission computed tomography (SPECT) study of a sleepwalker suggested activation of thalamocingulate pathways and persisting deactivation of other thalamocortical arousal systems, resulting in a dissociation between body sleep and mind sleep.58 The concept that the cortex itself can actually be a central pattern generator could explain the expression of previously learned behavior occurring during disorders of arousal.59
Sleep inertia (also termed sleep drunkenness) refers to a period of impaired performance and reduced vigilance following awakening from the regular sleep episode or from a nap. This impairment may be severe, last minutes to hours, and be accompanied by polygraphically recorded microsleep episodes.60–63 Support of a gradual disengagement from sleep to wakefulness comes from neurophysiologic studies in animals64 and cerebral blood flow studies in humans.65–67 The persistent reduction, lasting minutes, of the photomyoclonic response upon awakening from NREM sleep is further confirmation of a less-than-immediate transition from sleep to wakefulness.68 There appears to be great interindividual variability in the extent and duration of sleep inertia, both following spontaneous awakening after the major sleep period and following naps. Sleep inertia likely plays a role in the susceptibility to disorders of arousal.64
The cyclic alternating pattern (CAP) may also play a role in the etiology of disorders of arousal.69 CAP is a physiologic component of NREM sleep and is functionally correlated with long-lasting arousal oscillations. CAP is a measure of NREM instability, with high level of arousal oscillation.70 More sophisticated monitoring techniques, such as topographical EEG mapping, suggest that there may be more delta EEG activity before the onset of sleep terrors.71 There is no difference in the macrostructural sleep parameters between patients with disorders of arousal and controls. However, patients with disorders of arousal have been found to have increases in CAP rate, in number of CAP cycles, and in arousals with EEG synchronization. An increase in sleep instability and in arousal oscillation is a typical microstructural feature of slow-wave sleep–related parasomnias and may play a role in triggering abnormal motor episodes during sleep in these patients.72,73 Microarousals preceded by EEG slow-wave synchronization during NREM sleep are more common in patients with sleepwalking and sleep terrors than in controls. This supports the existence of an arousal disorder in these persons.72 Although some have reported hypersynchronous delta activity on polysomnograms (PSGs) of young adults with sleepwalking.74 this has not been the experience of others.75 EEG spectral analysis studies indicate that patients with sleepwalking demonstrate an instability of slow-wave sleep, particularly in the early portion of the sleep period.76 Impairment of efficiency of inhibitory cortical circuits during wakefulness has been reported.77
Disorders of arousal occur on a broad spectrum ranging from confusional arousals, through somnambulism (sleep walking), to sleep terrors (also termed pavor nocturnus and erroneously, incubus or succubus) (Videos 94-1 and 94-2). Some take the form of specialized behavior (discussed later) such as sleep-related eating and sleep-related sexual activity without conscious awareness.
Confusional arousals are often seen in children and are characterized by movements in bed, occasionally thrashing about, or inconsolable crying.78 Sleep drunkenness is probably a variation on this theme.17 The prevalence of confusional arousals in adults is approximately 4%.79
Sleepwalking is prevalent in childhood (1% to 17%), peaking at 11 to 12 years of age, and is far more common in adults (nearly 4%) than generally acknowledged.79–82 Sleepwalking may be either calm or agitated, with varying degrees of complexity and duration.
Sleep terrors are the most dramatic disorder of arousal. It is commonly initiated by a loud, blood-curdling scream associated with extreme panic, followed by prominent motor activity such as hitting the wall, running around or out of the bedroom, even out of the house—resulting in bodily injury or property damage. A universal feature is inconsolability. Although the victim appears to be awake, he or she usually misperceives the environment, and attempts at consolation are fruitless and might serve only to prolong or even intensify the confusional state. Some degree of perception may be evident, such as running for and opening a door or window. Complete amnesia for the activity is typical, but amnesia may be incomplete.11,12,83 The intense endogenous arousal and exogenous unarousability constitute a curious paradox. As with sleepwalking, sleep terrors are much more prevalent in adults than generally acknowledged (4% to 5%).84 Although usually benign, sleep terrors may be violent, resulting in considerable injury to the victim or others or damage to the environment, occasionally with forensic implications.85,86
The sleep-related eating disorder, characterized by frequent episodes of nocturnal eating, generally without full conscious awareness, usually not associated with waking eating disorders, likely represents a specialized form of disorder of arousal. This condition often responds to treatment with a combination of dopaminergic and opiate agents or topiramate.87 D-Fenfluramine, which is no longer available, has also been reported to be effective.88 Formal sleep studies are indicated, because sleep-related eating may be the manifestation of other sleep disorders such as restless legs syndrome, periodic limb movements of sleep, or obstructive sleep apnea, all of which predispose to arousal.89–94 Nocturnal binging may be induced by benzodiazepine medication.95 and sleep-related eating has been associated with zolpidem administration and olanzapine.96–98 The sleep-related eating disorder is distinct from the night-eating syndrome characterized by morning anorexia, evening hyperphagia (while awake), and insomnia and associated with hypothalamic-pituitary axis abnormalities.99–101