Insufficient Sleep Sleep Fragmentation Narcolepsy Recurrent Hypersomnias

Non-Pharmalogic Strategies Pharmalogic Treatment Sleep Disorder Summary

Human narcolepsy is a syndrome of unknown etiology. It is often described as a disorder of sleep-state boundary control and is characterized by the classic tetrad of EDS, cataplexy, hypnagogic / hypnopompic hallucinations, and sleep paralysis. Markedly disturbed nocturnal sleep, although not included in the original literature, is reported in up to 90% of patients and is more common than cataplexy in narcolepsy. Symptoms most often begin during adolescence or young adulthood; however, narcolepsy may also occur earlier in childhood or not until the third or fourth decade of life, or even later. EDS refers to a propensity to fall asleep, nod, or doze easily in relaxed or sedentary situations, or a need to exert extra effort to avoid sleeping in these situations. Unwanted sleepiness may also manifest as “sleep attacks” (irresistible urges to sleep), occurring not only during monotonous situations conducive to sleep, but also in situations where the patient is actively engaged in a task. In addition to frank sleepiness, the EDS can cause related symptoms, including poor memory, reduced concentration or attention, and irritability. Cataplexy is a sudden, partial or complete loss of voluntary muscle tone bilaterally in response to strong emotion, most often laughter, anger, or surprise (positive emotions are more commonly triggers for cataplexy). Startling stimuli, stress, physical fatigue, or sleepiness may also be important triggers or factors that exacerbate cataplexy. It may be subtle, occurring only in a few muscle groups and cause head drooping, slurred speech, or dropping things from the hand; or it may be so severe that total body paralysis occurs, resulting in complete collapse. The individual is usually alert and oriented during the spell, despite the inability to respond. There is usually complete recollection of the events. Cataplexy events usually last from a few seconds to 2 or 3 minutes, but occasionally continue longer.

Nocturnal Sleep Disruption: An often overlooked but important feature of narcolepsy is the experience of frequent nocturnal awakenings, often with difficulty returning to sleep.

Hypnagogic Or Hypnopompic Hallucinations: Hypnagogic and hypnopompic hallucinations are reported to be phenomena less common in narcolepsy than is cataplexy, but when present, often occur frequently. These sensory misperceptions occur at the transition from wakefulness to sleep (hypnagogic) or from sleep to wakefulness (hypnopompic) and are thought to result from the intrusion of dream-like brain activity into partial wakefulness. They may take many forms—visual, tactile, auditory, or multi-sensory events—and are usually brief (a minute or two) but occasionally can continue for a few minutes.

Sleep Paralysis: Similar to hypnagogic or hynopompic hallucinations, sleep paralysis occurs during the transition from sleep to wakefulness or vice versa. It is the inability to volitionally move any part of the body and can last from a few seconds to minutes.

Automatic Behavior: Automatic behavior can be described as “absent-minded” behavior or speech that is often nonsensical and that the patient does not remember. Automatic behavior occurs more often when the patient is sleepy.

Polysomnography (Nocturnal) And Multiple Sleep-Latency Test: Although not essential in the accurate diagnosis of narcolepsy when clear-cut cataplexy is present, polysomnography (PSG) is nonetheless important in the evaluation of narcolepsy of any form. PSG is used primarily to exclude other conditions that could be the cause of sleepiness or to evaluate the coexistence of other conditions adding to the sleepiness or nocturnal sleep disruption the patient may be experiencing. Obstructive sleep apnea, periodic limb movement activity during sleep, and rapid eye movement (REM) sleep behavior disorder are all more common in narcolepsy than in the general public.In narcolepsy, REM sleep upon falling asleep is common.
Daytime nap studies, in the form of the Multiple Sleep-Latency Test (MSLT), usually demonstrate a substantially reduced sleep latency. Typically, the mean sleep latency during four to five daytime nap opportunities is less than 5 minutes and almost always less than 8 or 9 minutes, compared with greater than 10 to 15 minutes in controls. Additionally, sleep-onset REM episodes usually occur during 50% or more of the daytime naps in patients with narcolepsy. Sleep-onset REM periods are not specific for narcolepsy but the occurrence of two or more of these events during the MSLT, in the setting of objective sleepiness and without another explanation for their occurrence, is strongly suggestive of narcolepsy.

Cerebrospinal fluid hypocretin (orexin) assessment: As is discussed later in the section on narcolepsy pathophysiology, many, but not all, patients with narcolepsy have very low or undetectable levels of hypocretin (orexin) in the cerebrospinal fluid (CSF). Such low levels of CSF hypocretin are not specific for narcolepsy and occur rarely in other neurologic conditions. However, when used to assess patients for narcolepsy, low CSF hypocretin is much more specific than is the finding of two or more sleep-onset REM episodes on MSLT.
Idiopathic Hypersomnia: Idiopathic Hypersomnia (also known as Idiopathic CNS Hypersomnia) is an incompletely defined disorder characterized by EDS. Traditionally, this diagnosis has been made for individuals with excessive somnolence but who lack the classic features of narcolepsy or another disorder known to cause EDS (such as sleep apnea). Without doubt, many patients have been diagnosed with idiopathic hypersomnia when in fact they have suffered from other disorders, such as narcolepsy without cataplexy, delayed sleep phase syndrome, or upper airway resistance syndrome . Typically, onset of symptoms occurs in adolescence or early adulthood. As denoted, the etiology of the disorder is not known, but viral illnesses, including Guillain-Barre syndrome, hepatitis, mononucleosis, and atypical viral pneumonia may herald the onset of sleepiness in a subset of patients. EDS may occur as part of the acute illness, but it persists after the other symptoms subside. Rarely, familial cases are known to occur, with increased frequency of HLA-Cw2 and HLA-DR11. Some of these patients have associated symptoms suggesting autonomic nervous system dysfunction, including orthostatic hypotension, syncope, vascular headaches, and peripheral vascular complaints. Most patients with idiopathic hypersomnia have neither a family history nor an obvious associated viral illness. Little is known about the pathophysiology of idiopathic hypersomnia. No animal model is available for study. Neurochemical studies using CSF have suggested that patients with idiopathic hypersomnia may have altered noradrenergic system function. Nocturnal sleep time tends to be long, and patients are usually difficult to awaken in the morning—they may become irritable or even abusive in response to the efforts of others to rouse them. In some patients, this difficulty may be substantial and may include confusion, disorientation, and poor motor coordination, a condition called “sleep drunkenness”. These patients often take naps, which may be prolonged but are usually non-refreshing. No amount of sleep relieves the EDS. “Microsleeps,” with or without automatic behavior, may occur throughout the day.

Polysomnographic studies of patients with idiopathic CNS hypersomnia usually reveal shortened initial sleep latency, increased total sleep time, and normal sleep architecture (in contrast to narcoleptic patients, who exhibit significant sleep fragmentation). Mean sleep latency on MSLT is usually reduced, often in the 8- to 10-minute range, but sometimes dramatically shorter. Also in contrast to narcolepsy, sleep-onset REM periods (SOREMPS) are not typically seen. Treatment of idiopathic CNS hypersomnia is usually less than satisfactory. Lifestyle and behavioral modifications, including good sleep hygiene, are appropriate, but treatment with stimulant or wake-promoting medication, as with narcolepsy, is usually necessary.