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6.06.2.1 Classification of Primary Sleep Disorders

Sleep disorders encompass a wide variety of clinical syndromes that prior to 1979 lacked a formal classification system. For instance, narcolepsy was considered a neurological disorder while insomnia was classified as a psychiatric disease. The International Classification of Sleep Disorders (ICSD) classified primary sleep disorders into two categories, the dyssomnias (insomnia or excessive sleepiness disorders) and parasomnias (abnormal behaviors or psychological events occurring during sleep) which are distinct from psychiatric sleep disorders.24 The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (Table 1) divides sleep disorders into four major categories by etiology: (1) primary sleep disorders; (2) sleep disorders related to other mental disorders; (3) sleep disorders due to general medical conditions; and (4) substance-induced sleep disorders.25

Primary sleep disorders are divided into the same two main categories as ICSD, dyssomnias and parasomnias. These are further subclassified: within dyssomnias primary insomnia, primary hypersomnia, narcolepsy, breathing-related sleep disorder, circadian rhythm sleep disorder, and dyssomnias not otherwise specified; parasomnia subdivisions include syndromes such as nightmare disorder, sleep terror disorder, sleepwalking disorder, and similarly parasomnias not otherwise specified (those falling outside of specific DSM-IV criteria). The three additional DSM-IV-TR sleep disorder categories are outside the scope of this review and are only briefly described. Sleep disorders related to other mental conditions (2), are viewed as integral to the pathophysiology of the specific mental disorder that affects sleep-wake activity indirectly. Sleep disregulation due to general medical conditions (3) may be the direct effect of a disease on sleep-wake regulation. Substance-induced sleep disorders (4) result from substance use/abuse or withdrawal.

Table 1 DSM-IV classification of primary sleep disorders

Dyssomnias

Primary insomnia 307.42 Primary hypersomnia 307.44 Narcolepsy 347

Breathing-related sleep disorder 780.59 Circadian rhythm sleep disorder 307.45 Dyssomnias not otherwise specified 307.47

Parasomnias

Nightmare disorder 307.47 Sleep terror disorder 307.46 Sleepwalking disorder 307.46 Parasomnia, not otherwise specified 307.47

6.06.2.2 Narcolepsy and Primary Hypersomnia

Hypersomnia manifests as a strong desire to sleep during the day or prolonged night-time sleep with difficulty awakening. Narcolepsy is the best known of the excessive somnolence disorders in which hypersomnia is a primary symptom. The essential feature of primary hypersomnia is a period (X 1 month) of excessive sleepiness characterized by daily episodes of sleepiness or prolonged sleep episodes. Sleep associated with primary hypersomnia although continuous, is not a recuperative process, therefore affected individuals do not easily recover from this unproductive sleep surplus. Nocturnal PSG evaluation of primary hypersomnia patients shows normal to prolonged sleep duration, reduced sleep latency, and generally normal REM/NREM sleep cycles (sleep architecture). While the actual prevalence of primary hypersomnia is unknown, it is less common than narcolepsy.26 Some 5-10% of patients presenting to sleep clinics with EDS symptoms are ultimately diagnosed as having primary hypersomnia with lifetime prevalence being as high as 16% with onset occurring at between 15-30 years and gradually progressing to a chronic and stable state without drug treatment.25 Recurrent hypersomnia is described by periods of excessive sleepiness lasting at least 3 days, several times over the course of a year and for a period of at least 2 years. The worldwide prevalence of narcolepsy is 1 in 2000 individuals, making it a common disorder.26

6.06.2.2.1 Excessive daytime sleepiness

Excessive daytime sleepiness (EDS) is frequently associated with nervous system disorders although excessive sleepiness may dominate the clinical presentation, despite a primary, underlying CNS pathology. Viral infections, structural lesions in the brain, head trauma, tumors, and a wide variety of other causative factors produce EDS. Infectious agents also cause sleepiness, the best known being trypanosomiasis (sleeping sickness). Excessive sleepiness is also associated with neurodegenerative diseases like Parkinson's and Alzheimer's disease. Narcolepsy syndrome is the best-known hypersomnolence condition with hallmark symptoms of hypersomnia and muscle weakness.26 A disabling neurological disorder, it is characterized by EDS, cataplexy, sleep paralysis, and hallucinations. Excessive, irresistible sleepiness must occur daily for a minimum period of 3 months to qualify the diagnosis of narcolepsy.

6.06.2.2.2 Cataplexy

Cataplexy is characterized by reversible episodes of bilateral loss of muscle tone without loss of consciousness. These episodes are sudden, last from seconds to minutes, and are precipitated by incidents of intense emotion or excitement, e.g., laughing, anger, fear, and surprise. Hypersomnia and cataplexy are two main features of narcolepsy.

6.06.2.2.3 Sleep paralysis

Sleep paralysis is a condition where an individual becomes immobilized during sleep and lacks the ability to move the head and limbs and may have difficulty breathing. Hallucinations can occur at sleep onset or at the onset of wakening.

The diagnosis of narcolepsy in 50-80% of patients is based on a clear association between hypersomnia and well-defined cataplexy. Nocturnal polysomnography coupled with the Multiple Sleep Latency Test (MSLT) indicates that narcoleptic patients display poorly organized sleep architecture, disordered sleep, short REM latency, and significant sleep-onset REM intrusions. The prevalence of narcolepsy-cataplexy is both societal and gender dependent.27

6.06.2.3 Primary Insomnia

Insomnia is difficulty in falling asleep, remaining asleep, early morning awakening, and/or sleep that is nonrestorative, all of which may lead to daytime consequences including fatigue, impaired cognition, irritability, mood disorders, and anxiety. It is among the most common of clinical complaints and can either be persistent or transient. A diagnosis of persistent insomnia should be aggressively managed due to significant attendant health concerns, e.g., depression and suicide, and precipitation of manic episodes in bipolar disorder.28 Insomnia is a cardinal symptom in depression and anxiety with treatment of the underlying psychiatric disorder frequently relieving the sleep disorder.

6.06.2.4 Circadian Rhythm Sleep Disorders

Shift work is classified according to different factors including continuity (continuous, semicontinuous, or discontinuous) and shift type (number of days spent during shift period, clockwise or counterclockwise rotation, and rotation cycle which describes the shift alternation). Syndromes falling under the general category of circadian rhythm sleep disorders include jet lag (time zone change) syndrome, shift work sleep disorder (SWSD), delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), irregular sleep-wake pattern (ISWP), and non-24

hour sleep-wake disorder (hypernycthemeral syndrome).7,29 These sleep disorders have a common basis through a mismatch in an individuals endogenous circadian cycle and the actual sleep demands (timing and duration), rather than a dysfunction of the specific mechanisms generating sleep and wakefulness. Jet lag syndrome and shift work sleep disorder are the most well recognized of the circadian rhythm syndromes. In jet lag syndrome, the traveler experiences difficulty sleeping due to changing time zones, particularly within a short period of time. Shift work sleep disorder is an important type of circadian rhythm disorder where an individual must change the normal bedtime, most commonly due to a change in work schedule (daytime to night-time and then reverse). In these circumstances the body does not readily adapt to these changes and individuals can suffer from either periods of insomnia or hypersomnia. Nearly 23% of subjects involved in shift work experienced a circadian shift disorder relative to individuals on a normal (daytime) work schedule.7 Delayed sleep phase type syndrome is characterized by delays in the bedtime whereby the patient cannot fall asleep until early in the morning resulting in waking much later in the day. This syndrome primarily affects adolescents. In advanced sleep phase type syndrome, the process is advanced compared to delayed sleep syndrome, and thus the bedtime is moved forward thereby causing difficulty in staying awake later and may be due to age-related changes in the circadian rhythm of an individual. Non-24 hour sleep-wake syndrome is a recently recognized somewhat rare sleep disorder. Individuals presenting with this disorder are either blind or have specific personality disorders, e.g., introversion with schizoid behavior. Irregular sleep-wake pattern is a sleep disorder most commonly found in nursing homes and in patients suffering from dementia.

6.06.2.5 Breathing-Related Sleep Disorders

Breathing-related sleep disorder syndrome is associated with sleep disruption with excessive sleepiness being a prominent symptom. Within the context of breathing-related sleep disorder, respiratory abnormalities fall into three distinct categories: apneas (breathing cessation), hypopneas (slow or shallow respiration), and hypoventilation (with abnormal oxygen and carbon dioxide levels). Breathing-related sleep disorder can also be subdivided into three types: obstructive sleep apnea syndrome (OSAS), central sleep apnea (CSA), and central alveolar hypoventilation syndrome. OSAS, the most common type of this sleep disorder, is characterized by episodes of apnea and hypopnea that repeat during the sleep phase, is more common in overweight individuals, and is associated with high morbidity and mortality.30 Given the close clinical correspondence between sleep hypopnea syndrome and sleep apnea syndrome, the syndrome is generally referred to as obstructive sleep apnea-hypopnea syndrome (OSAHS). Upper airway resistance syndrome (UARS) is a variant in which changes in ventilation are small and difficult to detect but for which the modest increase in airway resistance initiated a cascade of events producing symptoms similar to OSAHS.

Central sleep apnea syndrome has a similar presentation to OSAHS with periodic cessation of breathing followed by respiration, but without airway obstruction, and is more commonly observed in elderly patients where ventilation regulation may be compromised due to neurological or cardiac conditions. In central alveolar hypoventilation syndrome, control of ventilation is impaired resulting in lower arterial oxygen saturation, which may be further exacerbated by apneas and hypopneas. Individuals with breathing-related sleep disorder present with a variety of symptomatology including chest discomfort at night, choking or suffocation, and anxiety associated with apneas and difficult breathing. Patients complain of restless sleep with marginal recuperative value and feel worse upon waking than before falling asleep.

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