|Classification and external resources|
Narcolepsy //, also known as hypnolepsy, is a chronic neurological disorder caused by autoimmune destruction of hypocretin-producing neurons  inhibiting the brain's ability to regulate sleep-wake cycles normally. People with narcolepsy experience frequent excessive daytime sleepiness, comparable to how non-narcoleptics feel after 24 to 48 hours of sleep deprivation, as well as disturbed nocturnal sleep which often is confused with insomnia. Narcoleptics generally experience the REM stage of sleep within 5 minutes of falling sleep, while non-narcoleptics do not experience REM in the first hour or so of a sleep cycle until after a period of slow-wave sleep unless they are significantly sleep deprived. Another common symptom of narcolepsy is cataplexy, a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically (though not necessarily) triggered by emotions such as laughing, crying, terror, etc. affecting roughly 70% of people who have narcolepsy,.
The term narcolepsy derives from the French word narcolepsie created by the French physician Jean-Baptiste-Édouard Gélineau by combining the Greek νάρκη (narkē, "numbness" or "stupor"), and λῆψις (lepsis), "attack" or "seizure".
- 1 Classification
- 2 Signs and symptoms
- 3 Causes
- 4 Diagnosis
- 5 Treatment
- 6 Epidemiology
- 7 Society and culture
- 8 Research
- 9 See also
- 10 References
- 11 Sources
- 12 External links
The 2001 International Classification of Sleep Disorders (ICSD) divides primary hypersomnia syndromes between narcolepsy, idiopathic hypersomnia, and the recurrent hypersomnias (like Klein-Levin syndrome); it further divides narcolepsy into that with cataplexy and that without cataplexy. This ICSD version defines narcolepsy as “a disorder of unknown etiology that is characterized by excessive sleepiness that typically is associated with cataplexy and other REM-sleep phenomena, such as sleep paralysis and hypnagogic hallucinations". It also establishes baseline categorical standards for diagnosis of narcolepsy, through 2 sets of well defined criteria, as follows. Minimal narcolepsy diagnostic criteria set #2:
- A "complaint of excessive sleepiness or sudden muscle weakness."
- Associated features that include: sleep paralysis; disrupted major sleep episode; hypnagogic hallucinations; automatic behaviors.
- Polysomnography with one or more of the following: "sleep latency less than 10 minutes;" "REM sleep latency less than 20 minutes;" an MSLT with a mean sleep latency less than 5 minutes; "two or more sleep-onset REM periods" (SOREMPs).
- ”No medical or mental disorder accounts for the symptoms.” (see hypersomnia differential diagnosis)
In the absence of clear cataplexy, it becomes much more difficult to make a firm diagnosis of narcolepsy. “Various terms, such as essential hypersomnia, primary hypersomnia, ambiguous narcolepsy, atypical narcolepsy, etc., have been used to classify these patients, who may be in the developing phase of narcolepsy.” 
Since the 2001 ICSD, the classification of primary hypersomnias has been steadily evolving, as further research has shown more overlap between narcolepsy and idiopathic hypersomnia. The 3rd edition of the ICSD is currently being finalized, and its new classification will label narcolepsy caused by hypocretin deficiency as “type 1 narcolepsy,” which is almost always associated with cataplexy. The other primary hypersomnias will remain subdivided based on the presence of SOREMPs. They will be labeled: “type 2 narcolepsy,” with 2 or more SOREMPs on MSLT; and “idiopathic hypersomnia,” with less than 2 SOREMPS.
However, “there is no evidence that the pathophysiology or therapeutic response is substantially different for hypersomnia with or without SOREMPs on the MSLT.” Given this currently understood overlap of idiopathic hypersomnia and narcolepsy, the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) is also updating its classification of the primary hypersomnias. It reclassifies narcolepsy without cataplexy as major somnolence disorder (MSD). Additionally, MSD will encompass all syndromes of hypersomnolence not explained by low hypocretin, including idiopathic hypersomnia (with and without long sleep time) and long sleepers (patients requiring >10 hours sleep/day).
Further complicating these updated classification schemes, overlap between narcolepsy with cataplexy and idiopathic hypersomnia has also been reported. A subgroup of narcoleptics with long sleep time, comprising 18% of narcoleptics in one study, had symptoms of both narcolepsy with cataplexy and idiopathic hypersomnia (long sleep time and unrefreshing naps). It is felt that this subgroup might have dysfunction in multiple arousal systems, including hypocretin and GABA (see idiopathic hypersomnia causes).
Signs and symptoms
There are two main characteristics of narcolepsy: excessive daytime sleepiness and abnormal REM sleep. The first, excessive daytime sleepiness (EDS), occurs even after adequate night time sleep. A person with narcolepsy is likely to become drowsy or fall asleep, often at inappropriate times and places, or just be very tired throughout the day. Narcoleptics are not able to experience the amount of restorative deep sleep that healthy people experience – they are not "over-sleeping". In fact, narcoleptics live their entire lives in a constant state of extreme sleep deprivation. 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 few hours or less. Vivid dreams may be experienced on a constant or regular basis, even during very brief naps. Drowsiness may persist for prolonged periods of time or simply never cease. In addition, night-time sleep may be fragmented with frequent awakenings. A second prominent symptom of narcolepsy is abnormal REM sleep. Narcoleptics are unique in that they enter into the REM phase of sleep in the beginnings 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 patients.
- Cataplexy is an episodic condition featuring loss of muscle function, 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, and may last from a few seconds to several minutes. The person remains conscious throughout the episode. In some cases, cataplexy may resemble epileptic seizures. Usually speech is slurred and vision is impaired (double vision, inability to focus), 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.
- Sleep paralysis is the temporary inability to talk or move when waking (or less often, when falling asleep). It may last a few seconds to minutes. This is often frightening but is not dangerous.
- Hypnagogic hallucinations are vivid, often frightening, dreamlike experiences that occur while dozing, falling asleep. Hypnopompic hallucinations refer to the same sensations while awakening from sleep. These hallucinations may manifest in the form of visual or auditory sensations.
- Automatic behavior means that a person continues to function (talking, putting things away, etc.) during sleep episodes, but awakens with no memory of performing such activities. It is estimated that up to 40 percent of people with narcolepsy experience automatic behavior during sleep episodes. Sleep paralysis and hypnagogic hallucinations also occur in people who do not have narcolepsy, but more frequently in people who are suffering from extreme lack of sleep. 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 (failure to activate this protective paralysis) occurs in rapid eye movement behavior disorder.
- Night-time wakefulness is characterized by periods of wakefulness at night. These periods may be accompanied by hot flashes, elevated heart rate, and at times intense alertness.
In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime naps. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not. A rare subset of narcoleptics also experience heightened senses of taste and smell supertaster, phenomenon.
Although these are the common symptoms of narcolepsy, many people with narcolepsy also suffer from insomnia for extended periods of time. The symptoms of narcolepsy, especially 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. This sleep state is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again. This sleep state, called REM sleep (rapid eye movement sleep), is 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. Thus, narcolepsy is a disorder in which REM sleep appears at an abnormal time. Also, some of the aspects of REM sleep that normally occur only during sleep—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 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 (and out of) rapid eye movement (REM) sleep.
This has several consequences. Night time sleep does not include as much deep sleep, so the brain tries to "catch up" during the day, hence EDS. People with narcolepsy may visibly fall asleep at unpredicted moments (such motions as head bobbing are common). 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 (dizziness is a common occurrence). 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.
Although the cause of narcolepsy was not determined for many years after its discovery, scientists had discovered conditions that seemed to be associated with an increase in an individual's risk of having the disorder. Specifically, there appeared to be a strong link between narcoleptic individuals and certain genetic conditions. One factor that seemed to predispose an individual to narcolepsy involved an area of Chromosome 6 known as the HLA complex. There appeared to be a correlation between narcoleptic individuals and certain variations in HLA genes, although it was not required for the condition to occur. Certain variations in the HLA complex were thought to increase the risk of an auto-immune response to protein-producing neurons in the brain. The protein produced, called hypocretin or orexin, is responsible for controlling appetite and sleep patterns. Of the billions of cells in the human brain only about 10,000 to 20,000 cells secrete hypocretin molecules. Low levels of hypocretin have been correlated with a past history of infection, diet, contact with toxins such as pesticides, and brain injuries due to brain tumors or strokes.
Individuals with narcolepsy often have reduced numbers of these protein-producing neurons in their brains. In 2009 the autoimmune hypothesis was supported by research carried out at Stanford University School of Medicine.
The neural control of normal sleep states and the relationship to narcolepsy are only partially understood. In humans, narcoleptic sleep is characterized by a tendency to go abruptly from a waking state to REM sleep with little or no intervening non-REM sleep. The changes in the motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, spinal and brainstem alpha motor neuron hyperpolarization produces almost complete atonia of skeletal muscles via an inhibitory descending reticulospinal pathway. Acetylcholine may be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy has features normally seen only in normal REM sleep.
In 2004 researchers in Australia induced narcolepsy-like symptoms in mice by injecting them with antibodies from narcoleptic humans. The research has been published in the Lancet providing strong evidence suggesting that some cases of narcolepsy might be caused by autoimmune disease. Narcolepsy is strongly associated with HLA-DQB1*0602 genotype. There is also an association with HLA-DR2 and HLA-DQ1. This may represent linkage disequilibrium. Despite the experimental evidence in human narcolepsy that there may be an inherited basis for at least some forms of narcolepsy, the mode of inheritance remains unknown. Some cases are associated with genetic diseases such as Niemann-Pick disease or Prader-Willi syndrome.
Currently a link between GlaxoSmithKline's H1N1 flu vaccine Pandemrix and childhood narcolepsy is being investigated due to increased prevalence of narcolepsy in Irish, Finnish and Swedish children after vaccinations. Finland's National Institute of Health and Welfare is recommending that Pandemrix vaccinations be suspended pending further investigation into 15 reported cases of children developing narcolepsy. In Finland in mid-November 2010, 37 cases of children's narcolepsy had been reported by doctors. This can be compared to the normal average of 3 cases of children's narcolepsy per year. "The incidence of narcolepsy with cataplexy in children/adolescents in the Swedish population increased during the pandemic and vaccination period, with a rapid decline in incidence during the post pandemic period." Their conclusion is that these results "provide strengthened evidence that vaccination with Pandemrix during the pandemic period could be associated with an increase in the risk for narcolepsy with cataplexy in predisposed children/adolescents 19 years and younger."
In 2014, a study was published providing evidence that autoimmune CD4+ T-cells against HRCT epitopes may be a causative factor of the disease, as well as reinforcing the association with the influenza H1N1 vaccine.
A retrospective study of several hundred people in China reported that narcolepsy onset is highly correlated with seasonal patterns of upper airway infections, including H1N1 influenza.
Narcolepsy may represent an evolutionary atavism. According to a theory REM sleep is an evolutionary transformation of a well-known defensive mechanism, the tonic immobility reflex. This reflex, also known as animal hypnosis or death feigning, functions as the last line of defense against an attacking predator and consists of the total immobilization of the animal: the animal appears dead (cf. "playing possum"). The neurophysiology and phenomenology of this reaction shows striking similarities to REM sleep, a fact which betrays a deep evolutionary kinship. For example, both reactions exhibit brainstem control, paralysis, sympathetic activation, and thermoregulatory changes. This theory, which integrates many research findings into a unified and evolutionarily well informed framework, also sheds light on the phenomenon of narcolepsy.
Diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. It is also possible for cataplexy to occur in isolation. Three tests that are commonly used in diagnosing narcolepsy are the polysomnogram, the multiple sleep latency test (MSLT), and administration of the Epworth Sleepiness Scale. These tests are usually performed by a sleep specialist. The polysomnogram involves continuous recording of sleep brain waves and a number of nerve and muscle functions during nighttime sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may awaken often during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness.
The Epworth Sleepiness Scale is a brief questionnaire that is administered to determine the likelihood of the presence of a sleep disorder, including narcolepsy. For the multiple sleep latency test, a person is given a chance to sleep every 2 hours during normal wake times. The patient is taken in usually for an overnight sleep study. The following day the patient will have multiple tests where they will be told to nap after a full nights sleep (usually eight hours). Observations are made of the time taken to reach various stages of sleep (sleep onset latency). This test measures the degree of daytime sleepiness and also detects how soon REM sleep begins. Again, people with narcolepsy fall asleep rapidly and enter REM sleep early. Occasionally, a multiple sleep latency test can result in a false-negative for a narcoleptic.
Recent research has also revealed the possibility of measuring hypocretin levels in a patient's cerebrospinal fluid to diagnose narcolepsy, with abnormally low levels serving as a strong indicator of the disorder. This test can be useful when MSLT results are inconclusive or difficult to interpret. However, the test requires patients to undergo a spinal tap to actually extract the cerebrospinal fluid.
Patients with narcolepsy can be substantially helped, but not cured. Treatment is tailored to the individual, based on symptoms and therapeutic response. The time required to achieve optimal control of symptoms is highly variable, and may take several months or longer. Medication adjustments are frequently necessary, and complete control of symptoms is seldom possible. While oral medications are the mainstay of formal narcolepsy treatment, lifestyle changes are also important.
The main treatment of excessive daytime sleepiness in narcolepsy is central nervous system stimulants such as methylphenidate, amphetamine, methamphetamine, modafinil (Provigil), a new stimulant with a different pharmacologic mechanism, and/or armodafinil (Nuvigil). In Fall 2007 an alert for severe adverse skin reactions to modafinil was issued by the FDA. Other medications used are codeine and selegiline. Another drug that is used is atomoxetine (Strattera), a non-stimulant and norepinephrine reuptake inhibitor (NRI), that has little or no abuse potential. In many cases, planned regular short naps can reduce the need for pharmacological treatment of the EDS but only improve symptoms for a short duration. A 120-minute nap provided benefit for 3 hours in patient alertness where as a 15-minute nap provided no benefit. Daytime naps are not a replacement for nighttime sleep, especially if a person's body is natively inclined towards a nocturnal life cycle. Ongoing communication between the health care provider, patient, and the patient's family members is important for optimal management of narcolepsy.
Cataplexy and other REM-sleep symptoms are frequently treated with tricyclic antidepressants such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep. Venlafaxine (branded as Effexor XR by Wyeth Pharmaceuticals), an antidepressant which blocks the reuptake of serotonin and norepinephrine, has shown usefulness in managing symptoms of cataplexy, however, it has notable side-effects including sleep disruption.
Using stimulants to mask daytime sleepiness does not address the actual cause of the problem. Stimulants may provide some assistance with daytime activity, but the underlying cause will remain and potentially worsen over time due to the stimulant itself becoming an obstruction to delta wave sleep periods. Lifestyle changes involving reduced stress, more exercise (especially for overweight persons experiencing EDS caused by sleep apnea and snoring) and less stimulant intake (such as coffee and nicotine) are also used to manage the symptoms of narcolepsy.
In the United States, it is estimated that this condition afflicts as many as 200,000 Americans, but fewer than 50,000 are diagnosed. It is as widespread as Parkinson's disease or multiple sclerosis and more prevalent than cystic fibrosis, but it is less well known. Narcolepsy is often mistaken for depression, epilepsy, or the side effects of medications. It can also be mistaken for poor sleeping habits, recreational drug use, or laziness. Narcolepsy can occur in both men and women at any age, although its symptoms are usually first noticed in teenagers or young adults. There is strong evidence that narcolepsy may run in families; around 10 percent of people diagnosed with narcolepsy with cataplexy have a close relative with this neurological disorder. While narcolepsy symptoms are often confused with depression, there is a link between the two disorders. Research studies have mixed results on co-occurrence of depression in narcolepsy patients - the numbers quoted by different studies are anywhere between 6% and 50%.
Narcolepsy has its typical onset in adolescence and young adulthood. There is an average 15-year delay between onset and correct diagnosis which may contribute substantially to the disabling features of the disorder. Cognitive, educational, occupational, and psychosocial problems associated with the excessive daytime sleepiness of narcolepsy have been documented. For these to occur in the crucial teen years when education, development of self-image, and development of occupational choice are taking place is especially devastating. While cognitive impairment does occur, it may only be a reflection of the excessive daytime somnolence.
The prevalence of narcolepsy is about 1 per 2,000 persons. It is a reason for patient visits to sleep disorder centers, and with its onset in adolescence, it is also a major cause of learning difficulty and absenteeism from school. Normal teenagers often already experience excessive daytime sleepiness because of a maturational increase in physiological sleep tendency accentuated by multiple educational and social pressures; this may be disabling with the addition of narcolepsy symptoms in susceptible teenagers. In clinical practice, the differentiation between narcolepsy and other conditions characterized by excessive somnolence may be difficult. Treatment options are currently limited. There is a paucity in the literature of controlled double-blind studies of possible effective drugs or other forms of therapy. Mechanisms of action of some of the few available therapeutic agents have been explored but detailed studies of mechanisms of action are needed before new classes of therapeutic agents can be developed. Narcolepsy is an underdiagnosed condition in the general population. This is partly because its severity varies, so it can be mistaken for other illnesses very easily. Some people with narcolepsy do not suffer from loss of muscle control.
Society and culture
In the British television comedy-drama Doc Martin, the character Joe Penhale (played by John Marquez) is portrayed as having narcolepsy. In the 2007 video game Little Busters!, the protagonist Riki Naoe suffers from narcolepsy. In the 2014 Tamil movie Naan Sigappu Manithan(directed by Thiru) the lead character, played by Vishal, suffers from narcolepsy.
"Based on the role of histamine in keeping people awake (and hence the common side effect of anti-histamines such as diphenhydramine causing sleepiness), medications that act on histamine are under development for the treatment of excessive sleepiness." It remains to be seen whether or not these H3 antagonists (i.e., compounds such as pitolisant that promote the release of the wake-promoting amine histamine) will be particularly useful as wake-promoting agents.
Given the possible role of hyper-active GABAA receptors in the primary hypersomnias (narcolepsy and idiopathic hypersomnia), medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil.
Flumazenil is the only GABAA receptor antagonist on the market as of Jan 2013, and it is currently manufactured only as an intravenous formulation. Given its pharmacology, researchers consider it to be a promising medication in the treatment of primary hypersomnias. Results of a small, double-blind, randomized, controlled clinical trial were published in November 2012. This research showed that flumazenil provides relief for most patients whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA. For one patient, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several years. A 2014 case report also showed improvement in primary hypersomnia symptoms after treatment with a continuous subcutaneous flumazenil infusion. The supply of generic flumazenil was initially thought to be too low to meet the potential demand for treatment of primary hypersomnias. However, this scarcity has eased, and dozens of patients are now being treated with flumazenil off-label.
In a test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to return the function of the GABA system to normal in patients with primary hypersomnias. Investigators therefore treated a few patients with off-label clarithromycin, and most felt their symptoms improved with this treatment. In order to help further determine whether clarithromycin is truly beneficial for the treatment of narcolepsy and idiopathic hypersomnia, a small, double-blind, randomized, controlled clinical trial was completed in 2012. "In this pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. Larger trials of longer duration are warranted." In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of patients with GABA-related hypersomnia. “It is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained.”
Hypocretin antagonists (speculation that hypocretin agonist may be found)
Hypocretin-1 has been shown to be strongly wake-promoting in animal models, but it unfortunately does not cross the blood brain barrier. Therefore, companies are currently developing hypocretin receptor antagonists, like almorexant, which is awaiting FDA approval for the treatment of insomnia. It is also likely that a hypocretin-1 agonist will be found and developed for the treatment of hypersomnia.
Abnormally low levels of acylcarnitine have been observed in patients with narcolepsy. These same low levels have been associated with primary hypersomnia in general in mouse studies. “Mice with systemic carnitine deficiency exhibit a higher frequency of fragmented wakefulness and rapid eye movement (REM) sleep, and reduced locomotor activity.” Administration of acetyl-L-carnitine was shown to improve these symptoms in mice. A subsequent human trial found that narcolepsy patients given L-carnitine spent less total time in daytime sleep than patients who were given placebo.
- Caffeine-induced sleep disorder
- List of people with narcolepsy
- Sleep apnea
- Sleep inertia
- Sleep medicine
- Entry Narcolepsy-Causes in the University of Maryland Medical Center Harvey Simon, Associate Prof of Medicine, Harvard University & David Zieve, Medical Director of A.D.A.M, Inc.
- "Narcolepsy Information Page: National Institute of Neurological Disorders and Stroke (NINDS)". Ninds.nih.gov. 18 July 2013. Retrieved 3 March 2014.
- "What is Narcolepsy?". Retrieved 23 June 2014.
- "Narcolepsy Fact Sheet - NIH Publication No. 03-1637". National Institute of Neurological Disorders and Stroke. National Institutes of Health. Retrieved 5 August 2010.
- "REM sleep deprivation during 5 hours leads to an immediate REM sleep rebound and to suppression of non-REM sleep intensity.". Electroencephalogr Clin Neurophysiol. 1990 Aug;76(2):114-22. National Institutes of Health. Retrieved 6 June 2014.
- Seigal, Jerome (January 2001). "Narcolepsy". Scientific American: 77.
- "Narcolepsy Fact Sheet". Retrieved 2011-06-23.
- Entry Narcolepsy. in the Online Etymology Dictionary. Douglas Harper, Historian. 18 September 2007.
- "lepsy - Wiktionary". En.wiktionary.org. 8 June 2010. Retrieved 25 January 2011.
- "About Hypersomnia". Hypersomnia Foundation. Retrieved 25 January 2013.
- "International classification of sleep disorders, revised: Diagnostic and coding manual". American Academy of Sleep Medicine. 2001. Retrieved 25 January 2013.
- Bassetti, C (1997). "Idiopathic hypersomnia A series of 42 patients". Brain 120 (8): 1423. doi:10.1093/brain/120.8.1423.
- Mignot EJ (2012). "A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes". Neurotherapeutics 9 (4): 739–52. doi:10.1007/s13311-012-0150-9. PMC 3480574. PMID 23065655.
- "Diagnosis of Idiopathic Hypersomnia/ Major Hypersomnolence Disorder". Retrieved 23 April 2013.
- "Recent Updates to Proposed Revisions for DSM-5: Sleep-Wake Disorders". DSM-5 Development. American Psychiatric Association.
- Vernet, Cyrille (2009). "Narcolepsy with Long Sleep Time". Sleep.
- Green, Simon. Biological rhythms, sleep, and hypnosis. Basingstoke, Hampshire England: Palgrave Macmillan, 2011. Print.
- Kandel, Eric R.; James H. Schwartz, Thomas M. Jessell. Principles of Neural Science (4th ed.). McGraw-Hill. p. 949. ISBN 0-8385-7701-6.
- Narcolepsy MedicineNet.com
- Zorick FJ, Salis PJ, Roth T, Kramer M (1979). "Narcolepsy and automatic behavior: A case report". The Journal of clinical psychiatry 40 (4): 194–7. PMID 422531.
- Green, Simon. Biological rhythms, sleep, and hypnosis. Basingstoke, Hampshire [England: Palgrave Macmillan, 2011. Print.
- "Stanford: Narcolepsy Symptoms". med.stanford.edu. Retrieved 24 May 2012.
- Klein J, Sato A (September 2000). "The HLA system. Second of two parts". N. Engl. J. Med. 343 (11): 782–6. doi:10.1056/NEJM200009143431106. PMID 10984567.
- Mignot E (2001). "A commentary on the neurobiology of the hypocretin/orexin system". Neuropsychopharmacology 25 (5 Suppl): S5–13. doi:10.1016/S0893-133X(01)00316-5. PMID 11682267.
- Hallmayer J, Faraco J, Lin L, Hesselson S, Winkelmann J, Kawashima M, Mayer G, Plazzi G, Nevsimalova S, Bourgin P, Hong SC, Hong SS, Honda Y, Honda M, Högl B, Longstreth WT, Montplaisir J, Kemlink D, Einen M, Chen J, Musone SL, Akana M, Miyagawa T, Duan J, Desautels A, Erhardt C, Hesla PE, Poli F, Frauscher B, Jeong JH, Lee SP, Ton TG, Kvale M, Kolesar L, Dobrovolná M, Nepom GT, Salomon D, Wichmann HE, Rouleau GA, Gieger C, Levinson DF, Gejman PV, Meitinger T, Young T, Peppard P, Tokunaga K, Kwok PY, Risch N, Mignot E (June 2009). "Narcolepsy is strongly associated with the TCR alpha locus". Nat. Genet. 41 (6): 708–11. doi:10.1038/ng.372. PMC 2803042. PMID 19412176.
- "Narcolepsy is an autoimmune disorder, Stanford researcher says". EurekAlert!. American Association for the Advancement of Science. 3 May 2009. Retrieved 31 May 2009.
- "BBC News article". 13 December 2004. Retrieved 6 January 2010.
- Maret S, Tafti M (November 2005). "Genetics of narcolepsy and other major sleep disorders" (PDF). Swiss Medical Weekly (EMH Swiss Medical Publishers Ltd.) 135 (45–46): 662–5. PMID 16453205. Retrieved 7 March 2008.
- Vankova J, Stepanova I, Jech R, Elleder M, Ling L, Mignot E, Nishino S, Nevsimalova S (June 2003). "Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C". Sleep 26 (4): 427–30. PMID 12841368.
- Manni R, Politini L, Nobili L, Ferrillo F, Livieri C, Veneselli E, Biancheri R, Martinetti M, Tartara A (May 2001). "Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors". Clin Neurophysiol 112 (5): 800–5. doi:10.1016/S1388-2457(01)00483-7. PMID 11336895.
- "The MPA investigates reports of narcolepsy in patients vaccinated with Pandemrix". Swedish Medical Products Agency. 18 August 2010. Retrieved 19 August 2010.
- "Terveyden ja hyvinvoinnin laitos suosittaa Pandemrix-rokotusten keskeyttämistä". National Institute of Health and Welfare. 24 August 2010. Retrieved 24 August 2010.
- YLE News 17 November 2010: Ties Between Big Pharma and THL Draw Complaints
- Kugelberg, Elisabeth (21 January 2014). "Autoimmunity: A new clue to sleepiness". Nature Reviews Immunology 14 (2): 66–67. doi:10.1038/nri3609.
- De la Herrán-Arita AK, Kornum BR, Mahlios J, Jiang W, Lin L, Hou T, Macaubas C, Einen M, Plazzi G, Crowe C, Newell EW, Davis MM, Mellins ED, Mignot E (2013). "CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy". Sci Transl Med 5 (216): 216ra176. doi:10.1126/scitranslmed.3007762. PMID 24353159.
- Wood H (2011). "In brief". Nature Reviews Neurology 7 (10): 537. doi:10.1038/nrneurol.2011.134. PMID 21984118.
- Tsoukalas I (2012). "The origin of REM sleep: A hypothesis.". Dreaming 22 (4): 253–283.
- Vitelli, R. (2013). Exploring the Mystery of REM Sleep. Psychology Today, On-line blog, 25 March
- "Narcolepsy". Retrieved 17 December 2012.
- Thorpy MJ (1992). "The clinical use of the Multiple Sleep Latency Test. The Standards of Practice Committee of the American Sleep Disorders Association". Sleep 15 (3): 268–76. PMID 1621030.
- "Narcolepsy Research - FAQs". psychiatry.stanford.edu. Retrieved 13 September 2012.
- Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, Vankova J, Black J, Harsh J, Bassetti C, Schrader H, Nishino S (2002). "The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias". Archives of Neurology 59 (10): 1553–1562. doi:10.1001/archneur.59.10.1553. PMID 12374492.
- "Stanford: Narcolepsy Medications (Stanford)". med.stanford.edu. Retrieved 24 May 2012.
- Modafinil (marketed as Provigil): Serious Skin Reactions; FDA Drug Safety Newsletter
- Fry JM, Pressman MR, DiPhillipo MA, Forst-Paulus M (1986). "Treatment of narcolepsy with codeine". Sleep 9 (1 Pt 2): 269–74. PMID 3518019.
- Mayer G, Ewert Meier K, Hephata K (1995). "Selegeline hydrochloride treatment in narcolepsy. A double-blind, placebo-controlled study". Clin Neuropharmacol 18 (4): 306–19. doi:10.1097/00002826-199508000-00002. PMID 8665543.
- "Stanford Center for Narcolepsy article".
- Helmus T, Rosenthal L, Bishop C, Roehrs T, Syron ML, Roth T (1997). "The alerting effects of short and long naps in narcoleptic, sleep deprived, and alert individuals". Sleep 20 (4): 251–7. PMID 9231950.
- Caputo F, Zoli G (March 2007). "Treatment of narcolepsy with cataplexy". Lancet 369 (9567): 1080–1. doi:10.1016/S0140-6736(07)60523-6. PMID 17398302.
- "NAMI, National Alliance on Mental Illness, Effexor, Common Side Effects".
- "FDA Approval Letter for Xyrem; Indication: Cataplexy associated with narcolepsy; 17 Jul 2002".
- "FDA Approval Letter for Xyrem; Indication: EDS (Excessive Daytime Sleepiness) associated with narcolepsy; 18 Nov 2005".
- Wise MS, Arand DL, Auger RR, Brooks SN, Watson NF (Dec 2007). "Treatment of narcolepsy and other hypersomnias of central origin". Sleep 30 (12): 1712–27. PMC 2276130. PMID 18246981.
- Lifestyle and home remedies
- "Who Is At Risk for Narcolepsy?".
- "Link Between Narcolepsy and Mental Health". Retrieved 6 June 2014.
- "PC Joe Penhale | Doc Martin". Docmartinfan.com. Retrieved 3 March 2014.
- "Naan Sigappu Manithan - The Times of India". The Times Of India.
- "Hypersomnia Foundation - Treatment". Retrieved 25 January 2013.
- Lynn Marie Trotti, MD (9 August 2010). "Flumazenil for the Treatment of Primary Hypersomnia". Emory University - Georgia Research Alliance. ClinicalTrials.gov. Retrieved 25 January 2013.
- Lynn Marie Trotti, MD (15 June 2010). "Clarithromycin for the Treatment of Primary Hypersomnia". Emory University - Georgia Research Alliance. ClinicalTrials.gov. Retrieved 25 January 2013.
- Rye DB, Bliwise DL, Parker K, Trotti LM, Saini P, Fairley J, Freeman A, Garcia PS, Owens MJ, Ritchie JC, Jenkins A (21 November 2012). "Modulation of Vigilance in the Primary Hypersomnias by Endogenous Enhancement of GABAA Receptors". Sci. Transl. Med. 4 (161): 161ra151. doi:10.1126/scitranslmed.3004685. PMID 23175709.
- E. Kelty, V. Martyn, G. O’Neil and G. Hulse (19 February 2014). "Use of subcutaneous flumazenil preparations for the treatment of idiopathic hypersomnia: A case report". Journal of Psychopharmacology. doi:10.1177/0269881114523865.
- Beck, Melinda (2012-12-10). "Scientists Try to Unravel the Riddle of Too Much Sleep". The Wall Street Journal.
- "Hypersomnia Update". Emory University. Retrieved 2014-04-22.
- Trotti, L et al (June 2013). "CLARITHROMYCIN FOR THE TREATMENT OF HYPERSOMNIA: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL". Sleep 36 (Abstract Supplement): A248.
- Trotti LM, Saini P, Freeman AA, Bliwise DL, García PS, Jenkins A, Rye DB (2013). "Improvement in daytime sleepiness with clarithromycin in patients with GABA-related hypersomnia: Clinical experience". J. Psychopharmacol. (Oxford). doi:10.1177/0269881113515062. PMID 24306133.
- Miyagawa T, Miyadera H, Tanaka S, Kawashima M, Shimada M, Honda Y, Tokunaga K, Honda M (2011). "Abnormally low serum acylcarnitine levels in narcolepsy patients". Sleep 34 (3): 349–53A. PMC 3041711. PMID 21358852.
- Miyagawa T, Honda M, Kawashima M, Shimada M, Tanaka S, Honda Y, Tokunaga K (30 April 2009). "Polymorphism Located between CPT1B and CHKB, and HLA-DRB1*1501-DQB1*0602 Haplotype Confer Susceptibility to CNS Hypersomnias (Essential Hypersomnia)". In Rubinsztein, David C. PLoS ONE 4 (4): e5394. doi:10.1371/journal.pone.0005394. PMC 2671172. PMID 19404393.
- Miyagawa T, Kawamura H, Obuchi M, Ikesaki A, Ozaki A, Tokunaga K, Inoue Y, Honda M (2013). "Effects of oral L-carnitine administration in narcolepsy patients: A randomized, double-blind, cross-over and placebo-controlled trial". PLoS ONE 8 (1): e53707. doi:10.1371/journal.pone.0053707. PMC 3547955. PMID 23349733.
- Mitler MM, Hajdukovic R (June 1991). "Relative Efficacy of Drugs for the Treatment of Sleepiness in Narcolepsy". Sleep 14 (3): 218–20. PMC 2246380. PMID 1680245.
- Chabas D, Taheri S, Renier C, Mignot E (October 2003). "The Genetics of Narcolepsy". Annual Review of Genomics & Human Genetics 4: 459–83. doi:10.1146/annurev.genom.4.070802.110432. PMID 14527309.
- Smith AJ, Jackson MW, Neufing P, McEvoy RD, Gordon TP (2004). "A functional autoantibody in narcolepsy". Lancet 364 (9451): 2122–4. doi:10.1016/S0140-6736(04)17553-3. PMID 15589310.
|Wikimedia Commons has media related to Narcolepsy.|
- Narcolepsy Fact Sheet: National Institute of Neurological Disorders and Stroke
- Narcolepsy UK
- Narcolepsy Web site from the Harvard Medical School Division of Sleep Medicine