The two distinct sleep phases, REM and non-REM sleep have different neuroanatomic substrates. The cells that activate REM sleep are cholinergic neurons located in the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus in the pontomesencephalic region. These cells fire maximally during REM sleep. The cells that deactivate REM sleep are aminergic neurons located in the locus coeruleus and raphe nuclei. These cells are inactive during REM sleep. The reciprocal interaction in the brain stem between REM-activating and REM-deactivating neurons is responsible for REM generation and maintenance. The release of certain (, and ), is completely shut down during REM sleep. This causes a state called REM atonia, in which the are not stimulated and thus the body's are unable to move. Muscle atonia during REM sleep is further thought to result from active inhibition of motor activity by pontine centers (i.e. perilocus ceruleus) that exert an excitatory influence on the medulla (i.e. magnocellularis neurons) via the lateral tegmentoreticular tract. These neuronal groups then hyperpolarize the spinal motor neuron postsynaptic membranes via the ventrolateral reticulospinal tract. The eye movements associated with REM are generated by the nucleus with projections to the and are associated with pons, geniculate, occipital (PGO) waves. The cells that activate non-REM sleep are located primarily in the preoptic area of the hypothalamus, the basal forebrain area, and the solitary nucleus region of the medulla. The reticular nucleus of the thalamus is thought to be responsible for sleep spindle generation (Chokroverty, 2000).
Sleep disorders can result from disturbances of the circadian and homeostatic processes, from neurotransmitters imbalances or from degeneration or trauma to regions of the brain responsible for the regulation of sleep. Normally causes are less clear, except for sleeping sickness, a parasitic disease caused by trypanosoma, transmitted by the tse-tse fly. Sleep disorders can also be the consequence of medical or psychotic conditions such as depression, anxiety, panic or psychoses. Apart from sleeping sickness and secondary sleep disturbances, sleep disorders are broadly classified into dysomnias and parasomnias. Dysomnias are sleep disorders characterized a disturbance of the duration of sleep, for example, too much sleep (hypersomnias) or too little sleep (insomnias). They also include conditions such as narcolepsy, circadian rhythm sleep disorders, restless leg syndrome and obstructive sleep apnea. Parasomnias on the other hand are characterized by partial arousals during or during transitions between wakefulness and sleep. Unlike , parasomnias do not involve abnormalities of the mechanisms generating sleep-wake states, nor of the timing of sleep and wakefulness. Rather, parasomnias represent the activation of physiological systems at inappropriate times during the sleep-wake cycle. This could involve, for example, activation of the autonomic nervous system, motor system, or cognitive processes during sleep or sleep-wake transitions (Bear et al., 1996). Two of the most common parasomnias, REM sleep behaviour disorder (RBD) and sleepwalking will be investigated in detail.
RBD has only recently been recognised as a distinct clinical entity following a series of reports in 1986 (Schenck, Bundlie, Ettinger & Mahowald, 1986). Patients typically present complaining about acting out their violent dreams and while doing so harming themselves and their bed partners. The behaviours include punching, leaping or running out of bed while still in REM sleep. The patient may be wakened or may wake spontaneously during the attack and recall vividly the dream that corresponds to the physical action. RBD has strong relationships with many neurodegenerative disorders, such as Parkinson disease, multiple system atrophy and Lewy body disease. The incidence of RBD is increased in Parkinson disease (PD), and RBD may precede the development of PD by several years. However, the relationship between RBD and Parkinson disease is complex, as not all patients with RBD develop PD (Petit, Gagnon, Fantini, Ferini-Strambi & Montplaisir, 2004).
Under normal circumstances sleep paralysis prevents motor activity during REM sleep to ensure restful, inactive sleep during the most electrically active stage of sleep. It is a main feature of RBD that this muscle atonia during REM sleep is disrupted. As a result voluntary muscles become tonic, or tensely contracted, allowing a sleeping person to move his or her muscles during REM. The combination of heightened cerebral activity and muscular tonicity results in physically acting out dreams that involve excited and sometimes violent movement. People with RBD typically remember little nothing of this activity, unless they fall out of bed, bump into the furniture, or injure themselves and wake up. But they can usually remember and tell the dreams they were having during an episode. Dreams that involve violent or any other physical activity such as fighting, kicking, or running are more likely to trigger RBD activity (Schenck et al., 1986).
It is argued that the pedunculopontine nucleus (PPN) in the upper brainstem is involved in the disruption of REM atonia since it has strong links with the REM generator and atonia circuitry (Shouse & Siegel, 1992). Studies in dogs have identified a co-localisation of the atonia and locomotor systems in the pons, which provides an anatomic basis for the simultaneous dysregulation of tonic and phasic motor systems in RBD (Lai & Siegel, 1990). Studies with cats in the 1960s showed that bilateral lesions of the caudal and ventral pons (pontine tegmentum) resulted in loss of muscle atonia and dream enactment (hallucinatory sleep). The cats showed aggression, fear and rage during sleep but not during wakefulness. The fact that the cats’ behaviour after those lesions closely resembled that of patients with RBD further emphasized the link between the pons and muscle atonia. Further, the substantia nigra is closely connected to the REM generator circuitry and may play a major role in the genesis of PGO waves, which are a characteristic REM sleep event. Degeneration of substantia nigra and neuronal loss within the PPN were also found in patients with Parkinson’s disease, which could explain the close link between PD and RBD (Jellinger, 1991, as cited in Schenck & Mahowald, 2002).
The causes of RBD are still largely unknown. There is some evidence for a heritable component. Nightingale et al. (2005) found that 36% of people with narcolepsy experienced symptoms of RBD. In narcolepsy REM control mechanisms are also disturbed resulting in patients falling directly from wakefulness into REM sleep. This lead to an association of the disorders with HLA class II genes. Further, RBD may occur in association with various neurological conditions, such as Parkinson’s disease, multiple system atrophy, brainstem neoplasm, multiple sclerosis affecting the brainstem, olivopontocerebellar atrophy (OPCA), Dementia with Lewy bodies, Alzheimer dementia, progressive supranuclear palsy (PSP), or Shy-Drager syndrome (Uddin, 2007).
In the idiopathic form, RBD patients have no waking motor or cognitive complaints and their neurological examination is normal. In patients with associated neurodegenerative
diseases, RBD can precede the onset of the motor or cognitive symptoms by several years (Iranzo et al., 2005). In a clinical follow-up study of patients with RBD, Iranzo et al. found that 45% of those patients (which equaled 20 in total) developed a neurodegenerative disorder approximately 11.5 years after reported onset of RBD. Emerging disorders were Parkinson’s disease (PD) in nine cases, Dementia with Lewy bodies (DLB) in six cases, multiple system atrophy in one and mild cognitive (predominantly visio-spatial) impairment in four cases. This suggests that RBD could be an early characteristic of a common underlying neurological process. As mentioned earlier, the pathophysiology of RBD is associated with dysfunction of the lower brain stem nuclei which regulate REM sleep. The pathophysiology of Parkinson’s disease has been argued to begin in the medulla and spread upwards through the brainstem reaching the substantia nigra, the limbic structures including the amygdala, and finally the neocortex (Braak, del Tredici & Rub, 2003). A similar neuropathology has been suggested for dementia with Lewy bodies (Marui, Iseki & Nakai, 2002). The temporal sequence of the pathologies could explain why RBD might precede PD or DLB in some cases. Although there seems to be an obvious link between the pathologies of those disorders, the relationship between them is not straightforward. That is, some patients with these diseases might never develop RBD, or RBD develops after PD or dementia onset (Iranzo et al., 2005).
Sleepwalking refers to various complex motor behaviours that are initiated during sleep. Sleepwalkers engage not only in walking around; behaviours like dressing, eating, bathing or even driving a car have also been observed. Some episodes are limited to sitting up, picking bedclothes and mumbling. Patients are usually confused, disoriented, unresponsive, do not achieve full consciousness and they are very hard to wake up. Unless there has been a complete arousal, the patients are usually amnesic for the events in the morning (Kales et al., 1980). The duration of a sleep walking episode can last between a few minutes and hours. While some of the behaviours during sleepwalking can be similar to those exhibited during RBD they often lack the aggressive component of the latter. The main distinction between the two parasomnias, however, is that they occur during different phases of sleep. While RBD occurs exclusively during REM sleep, sleepwalking is an arousal disorders that occurs during non-REM sleep, predominantly in stages three and four. It is associated with frequent but incomplete awakening from slow-wave sleep. It was found that abrupt motor activity during episodes was associated with rhythmic delta waves in the EEG, which indicates a dissociation between motor and mental states of arousal (Broughton, 1968 as cited in Bassetti, Vella, Donati, Wielepp & Weder, 2000). A recent study using SPECT (single photon emission computed tomography) during sleepwalking suggests that this dissociation arises from activation of thalamocingulate pathways and persisting deactivation of other thalamocortical arousal systems. PET (positron emission tomography) studies in healthy adults have found that the hallmark of sleep (REM and non-REM) is a deactivation of prefrontal association cortices. Sleepwalkers also show deactivation in these areas but simultaneously they show activation in movement related areas like the posterior cingulated cortex and the anterior cerebellum, which is further evidence for a mind and motor arousal dissociation (Bassetti et al., 2000).
While RBD mostly occurs in older people, predominantly men; sleepwalking is a disorder mainly found in young people. The prevalence of sleepwalking decreases from 15% in children to only 1% in adults (Kavey, White, Resor & Gidro-Frank, 1990). Similar to RBD there seems to be a genetic component contributing to the risk of sleepwalking. A population based twin study by Hublin et al. (1997) suggests a genetic contribution for sleepwalking in more than a third of adults and more than half of children. Further, neurophysiological studies suggest inheritance of non-REM sleep instabilities with high levels of arousal caused by an innate instability of serotonin levels which in turn affects smooth transition through various sleep stages (Zucconi & Ferini-Strambi, 2000). Environmental factors were also found to contribute to the risk of sleepwalking. Those include illness, sleep deprivation, obstructive sleep apnoea, alcohol, hypnotics and psychotropic drugs, shift work, emotional stress and psychopathology (Zaiwalla, 2005).
Patients who sleepwalk often suffer from another parasomnia as well, which is referred to as sleep terror. In fact, they seem to be two aspects of the same pathophysiological state. Both parasomnias occur in the first third of the night. In sleep terror, patients suddenly sit up in their bed and start screaming. In both conditions patients are confused, disoriented, unresponsive and are very hard to wake up. Both conditions are considered to be disorders of arousal with a dissociation between motor and cortical activity (Espa et al., 2000). The inability to maintain non-REM sleep, with frequent arousals during slow wave sleep has also been noted in patients with a diagnosis of sleep apnea and restless leg movements in sleep. However, despite the common non-REM instability of those disorders apnea and restless leg patients rarely have a history of sleepwalking. A recent study by Guilleminault et al. (2006) found that the pattern of arousals in sleepwalkers was virtually indistinguishable from those of patients with Upper Airway Resistance Syndrome. They therefore suggested that a careful analysis of sleep disordered breathing should be undertaken to account for the arousals. That is, breathing abnormalities should be ruled out before assuming a brain related abnormality.
For the clinician the easiest way to distinguish between RBD and sleepwalking is by asking patients what they recall after the episode. Patients with RBD generally recall their dreams, which often involve aggressive feelings, very well. Patients that sleepwalk generally have no memory of their nocturnal activity (unless they have woken up properly during the episode). However, not all non-REM sleep is completely dreamless so that some people could recall a dream after an episode. In these cases, a family history of sleepwalking is an additional indicator for a patient’s likelihood of suffering from the disorder. Should results still be inconclusive a polysomnography should be carried out. A polysomnography involves patients sleeping in a sleep laboratory while a video records of their activity of the night. Further, EEG, EMG and electro-oculogram (EOG) are recorded during sleep. In a later analysis it can be determined in what sleep phase the patient was when becoming active during the night. If the patient was in REM sleep when getting up and moving around the diagnosis would be RBD. Further evidence is provided by the EMG, which should show muscle tension and the EOG, which should show rapid eye movements during the REM phase. In case of sleepwalking patients should have their active episode immediately following slow wave sleep.
RBD is a treatable condition. Medication with clonazepam is effective in nearly 90% of patients (complete benefit in 79% of patients and partial benefit in another 11% of patients), with little evidence of tolerance or abuse (Uddin, 2007). However, due to the strong relationship of RBD with other neurodegenerative disorders therapists should consider that RBD symptoms are manifestations of these disorders. Therefore careful follow-up monitoring is requested. For sleepwalking treatment is very limited. It mainly involves creating a safe environment for the sleeper such as having little furniture in the bedroom and locking doors and windows.
Conclusion
Sleep is a state of rest which is necessary for survival. During sleep there is a cyclic change in brain activity between relaxed (non-REM) and highly active (REM) states. These cyclic changes are regulated by structures in the brain stem, thalamus and hypothalamus using different neurotransmitter systems. Abnormalities in these brain structures and neurotransmitter imbalances can lead to sleep disturbances known as parasomnias. Sleepwalking and RBD are two examples which may seem similar regarding their symptoms but differ substantially in their pathologies. The main distinction between them is that episodes are happening in different phases of sleep (in non-REM for sleepwalking and REM for RBD). For both, a heritable component is suggested but causes remain largely unknown. In addition to reports from patients and their partners about sleeping habits, polysomography is the most efficient tool for distinguishing between the two parasomnias. This distinction is not only important with regards to subsequent treatment. It also has significant implications for patients’ future prognoses since RBD is a key indicator for neurodegenerative disorders, which can develop as much as 13 years after diagnosis of RBD.
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