122 Narcolepsy (347.00)

DSM-IV-TR criteria

A. Irresistible attacks of refreshing sleep that occurs daily over at least 3 months.

B. The presence of one or both of the following:

Cataplexy (brief episodes of sudden bilateral loss of muscle tone, which is most often associated with intense emotion.)

Recurrent intrusions of elements of rapid eye movement (REM) sleep into the transition between sleep and wakefulness, as manifested by either hypnopompic or hypnagogic hallucinations or sleep paralysis at the beginning of end of sleep episodes.

C. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or another general medical condition.

Associated features

Narcolepsy is a neurological disorder in which the brain conveys sleep evoking signals at unexpected and inappropriate times. People with narcolepsy experience an inadequate order and length of NREM and REM sleep stages which are disrupted REM sleep episodes during sleep onset instead of after NREM sleep. During a time of excessive sleepiness, an individual with narcolepsy may temporarily experience muscle instability leading to paralysis or cataplexy of the head and body while the person remains awake and entirely conscious. Symptoms also include hypnagogic hallucinations, automatic behavior, insomnia and fragmented sleep associated with excessive day time sleepiness (EDS). Occurrences of narcolepsy may be prompted by sudden emotional reactions such as anger, surprise, fear, or even laughter. The episodes can last anywhere from several seconds to several minutes. Approximately forty percent of individuals with narcolepsy experience comorbidity with depression, anxiety, or substance-related abuse, and some may also experience all symptomatologies associated with narcolepsy.

Child vs. adult presentation

Narcolepsy can occur in children as young as five, but is more prominent during adolescence, though it is also possible for it to develop during young adulthood. Children with narcolepsy also suffer from excessive daytime drowsiness and cataplexy which is most often described as fainting in young children. Children frequently exert confusion and aggressive behaviors when woken up. Frequently, narcolepsy is misdiagnosed in children as a learning disability or attention deficit disorder. However, narcolepsy is usually more difficult to identify in children.

Gender and cultural differences in presentation

Narcolepsy is prevalent in relatively equal rates among males and females; however it has a genetic component that predisposes individuals to develop narcolepsy. Having a close relative that has narcolepsy increases an individual’s risk of developing the disorder by anywhere from twenty to forty times. There are very few variations in the severity and appearance of symptoms between different ethnic groups. Asians usually tend to report less severe incidents of negative emotions and hostility associated with narcolepsy, whereas Caucasian patients tend to report higher rates of cataplexy than many other ethnic groups.

Epidemiology

Studies have shown that Narcolepsy can be found anywhere between 25 and 50 per 100,000 people in European countries, Japan, and the US. Therefore about one in two thousand Americans suffer from narcolepsy. Still the exact prevalence rate continues to remain unclear and the disorder may perhaps affect a bigger section of the population than what is currently estimated.

Etiology

Many advances in determining the cause of narcolepsy have been made in recent years, but a direct causation has not yet been established. Most people who have narcolepsy have low levels of hypocretin, which is a chemical that helps control the level of a person’s wakefulness. The reason for low hypocretin levels, however, is unknown. The main consensus among researchers is genetics. Some scientists think narcolepsy could also be caused by various environmental stressors that occur before the age of onset in the genetically opportunistic individuals. Some factors that could influence development are the individuals BMI, immune response, and other stressful life events. These triggers are still being activated.

Empirically supported treatments

• Since there is not a cure for narcolepsy, clinicians strive to improve the patient’s alertness as well as attentiveness during the daytime. Stimulants, antidepressants, and anticataplectics are the types of medications currently used to treat narcolepsy. Stimulants have been around for the longest period of time. Antidepressants are used to suppress the REM sleep and they can help prevent cataplexy, hypnagogic hallucinations, and sleep paralysis. The two types of antidepressants that are commonly used are the selective serotonin reuptake inhibitors (SSRI’s) and tricyclics. GHB, or gammahydroxybutyrate (also known as Sodium oxybate [Xyrem]), gained FDA approval in the year 2002. It is the only drug of its kind (anticataplectic) used to treat patients that experience cataplexy caused by narcolepsy. The Food and Drug and Administration approved a drug called modafinil for excessive daytime sleepiness.
• Behavioral treatments have also been studied. Adjustments in life-style are necessary for improvement. Some suggestions include following a strict sleep-wake schedule; taking short naps one or two times each day; increasing physical activity and avoiding repetitive tasks as well as potentially dangerous activities such as diving, swimming, and cooking unless under supervision or at a peak alert time.

Proposed DSM-5 Changes (dsm5.org)

Narcolepsy/Hypercretin Deficiecy

A. Recurrent daytime naps or lapses into sleep that occurs daily or almost daily over at least the last 3 months (when the patient is untreated).
B. The presence of one or both of the following:
1. Cataplexy defined as brief (a few seconds to 2 minutes) episodes of sudden bilateral loss of muscle tone with maintained consciousness, most often in association with laughter or joking. These episodes must occur at least a few times per month providing the patient is untreated for this symptom.
2. Hypocretin deficiency, as measured using CSF hypocretin-1 immunoreactivity measurements (<1/3 of normal reference values).

C. Do not occur exclusively during the course of another mental or medical disorder but may occur simultaneously with these disorders.
Rationale: In 2000, it was discovered that most cases with narcolepsy-cataplexy have hypocretin deficiency. Animal models without hypocretin have narcolepsy, establishing causality. Advantage: the name “narcolepsy/hypocretin deficiency” now encompasses a real disease entity with a single etiology and generally consistent set of symptoms. Therapy is more codified for this entity, which was previously “contaminated” by 20-50% (depending of the case series) of patients with other problems. Disadvantage: Some patients with “narcolepsy” but without cataplexy/hypocretin deficiency (generally narcolepsy without cataplexy) could be “undiagnosed”. To mitigate this problem, we insist that the category 307.44 “Primary hypersomnia” be renamed “primary hypersomnia/narcolepsy without cataplexy”

Criterion B2

Rationale: Recurrent intrusions of elements of REM sleep such as “hypnopompic or hypnagogic hallucinations or sleep paralysis at the beginning or end of sleep episodes” have been shown to occur frequently in normal individuals (especially after sleep deprivation/interruptions), and to be frequently absent in genuine narcoleptic patients. It is neither specific nor sensitive and must be deleted. In contrast, measuring CSF hypocretin-1 immunoreactivity identifies the actual cause of the symptomatology (title change). It also has only very few false positive in patients without a serious associated neurological condition (~0.1%). Advantage: Fewer patients will be diagnosed for life as “narcoleptic” and treated with stimulants unnecessarily if not carelessly. Disadvantage: Some patients diagnosed as “narcolepsy” because they were sleepy and had some sleep paralysis, and hypnagogic hallucinations could feel they are being undiagnosed. To mitigate this problem, we insist that the category 307.44 “Primary hypersomnia” be renamed “primary hypersomnia/narcolepsy without cataplexy”.
A question may be whether or not a positive Multiple Sleep Latency Test (MSLT mean sleep latency ≤8 min, ≥2 Sleep onset REM periods), a nap sleep polysomnography test that has been developed to diagnose narcolepsy, should be added as a third possible criteria. The MSLT is reasonably sensitive (95%) for narcolepsy/cataplexy with hypocretin deficiency. Problematically however, two recent studies have shown it is not very specific, being positive in approximately 2-4% of the general population and probably more in patients with sleep apnea, sleep deprivation or other sleep disorders. Many normal subjects who do not complaint of any symptoms are positive for the test. As the MLT is increasingly used to diagnose narcolepsy independently of the clinical picture, an epidemic of “narcolepsy with cataplexy cases” defined with by a positive MSLT alone is now being diagnosed and aggressively treated, often inappropriately. These subjects often think they have a life long biochemical condition, which is not established. In the revised classification, these subjects will be pulled with “primary Hypersomnia cases”, a mixed bag of cases with sleepiness or excessive sleep of unknown etiologies.
Of note, as it is, the revised classification will remain similar to that of the International Classification of sleep Disorders (ICSD2), except that two instead of 4 categories are included. Narcolepsy/cataplexy would roughly correspond to narcolepsy-cataplexy/hypocretin deficiency. Primary hypersomnia/narcolepsy without cataplexy will be a category merging ICSD2 narcolepsy without cataplexy, hypersomnia with long sleep time, and narcolepsy without long sleep time. As these three entities are not known to be pathophysiologically distinct, and are treated and evaluated similarly, the DSMV will be easier to use than the ICSD2.

Relationship to International Classification of Diseases-10

Narcolepsy and Cataplexy G47.4

Relationship to International Classification of Sleep Disorders 2nd Edition

The revised classification will remain similar to that of the ICSD-2, except that two instead of 4 categories are included. Narcolepsy/cataplexy would roughly correspond to narcolepsy-cataplexy/hypocretin deficiency. idiopathic hypersomnia, with/without long sleep time, 327.11, 327.12; narcolepsy with cataplexy 347.01

Severity 

1. Stanford Sleep Inventory (1)
2. Epworth sleepiness Scale
3. Multiple Sleep Latency Test

4. Maintenance of Wakefulness test