Narcolepsy
Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM sleep. The symptoms of narcolepsy include excessive daytime sleepiness, sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep, and cataplexy. People with narcolepsy typically have poor quality of sleep.
There are two recognized forms of narcolepsy: type 1 and type 2. Narcolepsy type 1 can be clinically characterized by symptoms of EDS and cataplexy, and/or will have cerebrospinal fluid orexin levels of less than 110 pg/ml. Cataplexy is transient episodes of aberrant muscle tone, most typically loss of muscle tone, that may be associated with strong emotion. In pediatric-onset narcolepsy, active motor phenomena are not uncommon. Cataplexy may be mistaken for syncope, tics, or seizures. Narcolepsy type 2 does not have features of cataplexy, and CSF orexin levels are normal. Sleep-related hallucinations, both hypnagogic and hypnopompic, are vivid hallucinations that can be auditory, visual, or tactile and may occur independent of or in combination with an inability to move.
Narcolepsy is a clinical syndrome of hypothalamic disorder, but the exact cause of narcolepsy is unknown, with potentially several causes. A leading consideration for the cause of narcolepsy type 1 is that it is an autoimmune disorder. Proposed pathophysiology as an autoimmune disease suggest antigen presentation by DQ0602 to specific CD4+ T cells resulting in CD8+ T-cell activation and consequent injury to orexin producing neurons. Familial trends of narcolepsy are suggested to be higher than previously appreciated. Familial risk of narcolepsy among first-degree relatives is high. Relative risk for narcolepsy in a first-degree relative has been reported to be 361.8. However, there is a spectrum of symptoms found in this study, from asymptomatic abnormal sleep test findings to significantly symptomatic.
The autoimmune process is thought to be triggered in genetically susceptible individuals by an immune-provoking experience, such as an infection with H1N1 influenza. Secondary narcolepsy can occur as a consequence of another neurological disorder. Secondary narcolepsy can be seen in some individuals with traumatic brain injury, tumors, Prader–Willi syndrome or other diseases affecting the parts of the brain that regulate wakefulness or REM sleep. Diagnosis is typically based on the symptoms and sleep studies, after excluding alternative causes of EDS. EDS can also be caused by other sleep disorders such as insufficient sleep syndrome, sleep apnea, major depressive disorder, anemia, heart failure, and drinking alcohol.
While there is no cure, behavioral strategies, lifestyle changes, social support, and medications may help. Lifestyle and behavioral strategies can include identifying and avoiding or desensitizing emotional triggers for cataplexy, dietary strategies that may reduce sleep-inducing foods and drinks, scheduled or strategic naps, and maintaining a regular sleep-wake schedule. Social support, social networks, and social integration are resources that may lie in the communities related to living with narcolepsy. Medications used to treat narcolepsy primarily target EDS and/or cataplexy. These medications include alerting agents, oxybate medications, and other stimulants. There is also the use of antidepressants such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin–norepinephrine reuptake inhibitors for the treatment of cataplexy.
Estimates of frequency range from 0.2 to 600 per 100,000 people in various countries. The condition often begins in childhood, with males and females being affected equally. Untreated narcolepsy increases the risk of motor vehicle collisions and falls.
Narcolepsy generally occurs anytime between early childhood and 50 years of age, and most commonly between 15 and 36 years of age. However, it may also rarely appear at any time outside of this range.
Signs and symptoms
There are two main characteristics of narcolepsy: excessive daytime sleepiness and abnormal REM sleep. Excessive daytime sleepiness occurs even after adequate night time sleep. A person with narcolepsy is likely to become drowsy or fall asleep, often at inappropriate or undesired times and places, or just be very tired throughout the day. Narcoleptics may not be able to experience the amount of restorative deep sleep that healthy people experience due to abnormal REM regulation – they are not "oversleeping." Narcoleptics typically have higher REM sleep density than non-narcoleptics, but also experience more REM sleep without atonia. Many narcoleptics have sufficient REM sleep, but do not feel refreshed or alert throughout the day. This can feel like living their entire lives in a constant state of sleep deprivation.Excessive sleepiness can vary in severity and appears most commonly during monotonous situations that require little interaction. Daytime naps may occur with little warning and may be physically irresistible. These naps can occur several times a day. They are typically refreshing, but only for a brief period. Vivid dreams may be experienced regularly, even during short naps. Drowsiness may persist for prolonged periods or remain constant. Additionally, nighttime sleep may be fragmented, with frequent awakenings. A second prominent symptom of narcolepsy is abnormal REM sleep. Narcoleptics are unique in that instead of following the typical sleep cycle, they enter into the REM phase of sleep at the beginning of sleep, even when sleeping during the day.
The classic symptoms of the disorder, often referred to as the "tetrad of narcolepsy", are cataplexy, sleep paralysis, hypnagogic hallucinations, and excessive daytime sleepiness. Other symptoms may include automatic behaviors and night-time wakefulness. These symptoms may not occur in all people with narcolepsy.
- An episodic loss of muscle function, known as cataplexy, ranging from slight weakness such as limpness at the neck or knees, sagging facial muscles, weakness at the knees often referred to as "knee buckling", or inability to speak clearly, to a complete body collapse. Episodes may be triggered by sudden emotional reactions such as laughter, anger, surprise, or fear. The person remains conscious throughout the episode. In some cases, cataplexy may resemble epileptic seizures. Usually, speech is slurred and vision is impaired, but hearing and awareness remain normal. Cataplexy also has a severe emotional impact on narcoleptics, as it can cause extreme anxiety, fear, and avoidance of people or situations that might elicit an attack. Cataplexy is generally considered to be unique to narcolepsy and is analogous to sleep paralysis in that the usually protective paralysis mechanism occurring during sleep is inappropriately activated. The opposite of this situation occurs in rapid eye movement behavior disorder.
- Periods of wakefulness at night.
- The temporary inability to talk or move when waking, known as sleep paralysis. It may last a few seconds to minutes. This is often frightening but is not dangerous.
- Vivid, often frightening, dreamlike experiences that occur while dozing or falling asleep, known as hypnagogic hallucinations. Hypnopompic hallucinations refer to the same sensations while awakening from sleep. These hallucinations may manifest in the form of visual or auditory sensations.
Many people with narcolepsy also have insomnia for extended periods. The excessive daytime sleepiness and cataplexy often become severe enough to cause serious problems in a person's social, personal, and professional life. Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular, which is called non-rapid eye movement sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again, called REM sleep, when most remembered dreaming occurs. Associated with the EEG-observed waves during REM sleep, muscle atonia is present, called REM atonia.
In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Also, some aspects of REM sleep that normally occur only during sleep, like lack of muscular control, sleep paralysis, and vivid dreams, occur at other times in people with narcolepsy. For example, the lack of muscular control can occur during wakefulness in a cataplexy episode; it is said that there is an intrusion of REM atonia during wakefulness. Sleep paralysis and vivid dreams can occur while falling asleep or waking up. Simply put, the brain does not pass through the normal stages of dozing and deep sleep but goes directly into rapid eye movement sleep.
As a consequence, nighttime sleep does not include as much deep sleep, so the brain tries to "catch up" during the day, hence excessive daytime sleepiness. People with narcolepsy may visibly fall asleep at unpredictable moments. People with narcolepsy fall quickly into what appears to be very deep sleep, and they wake up suddenly and can be disoriented when they do. They have very vivid dreams, which they often remember in great detail. People with narcolepsy may dream even when they only fall asleep for a few seconds. Along with vivid dreaming, people with narcolepsy are known to have audio or visual hallucinations before falling asleep or before waking up.
Narcoleptics can gain excess weight; children can gain when they first develop narcolepsy; in adults, the body-mass index is about 15% above average.