Narcolepsy is a long-term neurological disorder involving decreased ability to regulate sleep-wake cycles. Symptoms include periods of excessive daytime sleepiness that usually last from minute to minute and can happen anytime. About 70% of those affected also experience episodes of sudden muscle loss, known as cataplexy. These experiences can be caused by strong emotions. Less commonly, there may be an inability to move or light hallucinations while asleep or waking. People with narcolepsy tend to sleep about the same number of hours per day as people without, but sleep quality tends to be worse.
The exact cause of narcolepsy is unknown, with the possibility of several causes. In up to 10% of cases, there is a family history of the disorder. Often, those affected have low levels of orexin neuropeptides, which may be caused by an autoimmune disorder. Trauma, infection, poison or psychological pressure can also play a role. Diagnosis is usually based on symptoms and sleep studies, having ruled out other potential causes. Excessive daytime sleepiness can also be caused by other sleep disorders such as sleep apnea, major depressive disorders, anemia, heart failure, drinking alcohol and sleep deprivation. Cataplexy may be mistaken for seizures.
Although there is no cure, a number of lifestyle changes and medications can help. Lifestyle changes include a short nap on a regular basis and sleep hygiene. Medications used include modafinil, sodium oxybate and methylphenidate. Although initially effective, tolerance to benefits can develop over time. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) can improve cataplexy.
Approximately 0.2 to 600 per 100,000 people are affected. This condition often begins in childhood. Men and women are affected equally. Untreated narcolepsy increases the risk of motor vehicle crashes and falls. The term "narcolepsy" comes from the French narcolepsy . The French term was first used in 1880 by Jean-Baptiste-ÃÆ' â € ° douard GÃÆ'Ã… © lineau, which uses Greek ????? ( nark? ), meaning "numbness", and ????? ( lepsis ) which means "attack".
Video Narcolepsy
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 a good night's sleep. A person with narcolepsy tends to become drowsy or asleep, often at inappropriate times and places, or just feeling very tired all day long. Narcoleptics can not experience the amount of restorative restful sleep experienced by healthy people - they do not "overeat". In fact, narcoleptics live their entire lives in a state of constant sleep deprivation.
Napping can occur with a few warnings and may be physically irresistible. This nap can happen several times a day. They are usually refreshing, but only for a few hours or less. Living dreams may be experienced on a regular basis, even during a very short nap. Drowsiness may persist for a long time or remain constant. In addition, night sleep may be fragmented, with frequent waking. The second prominent symptom of narcolepsy is abnormal REM sleep. Narcoleptics are unique because they enter the REM sleep phase in early sleep, even when sleeping during the day.
The classic symptoms of this disorder, often referred to as "tetrad of narcolepsy", are cataplexy, sleep paralysis, hypnagogic hallucinations, and excessive daytime sleepiness. Other symptoms may include automatic behavior and night waking. These symptoms may not occur in all patients. Cataplexy is a loss of episodic muscle function, ranging from mild weaknesses such as weakness in the neck or knee, loose facial muscles, weakness of the knee often referred to as "knee bend", or inability to speak clearly. , to 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, cataplasia may resemble epileptic seizures. Usually lisp and eyesight is disturbed (double vision, inability to focus), but hearing and consciousness remain normal. Cataplexy also has a severe emotional impact on narcolepsy, as it can cause extreme anxiety, fear, and avoidance of people or situations that might cause an attack. Cataplexy is generally considered unique to narcolepsy and is analogous to sleep paralysis because the mechanism of paralysis that usually occurs during sleep is not properly activated. The opposite of this situation (failure to activate this protective paralysis) occurs in rapid eye movement disorder.
In most cases, the first symptoms of narcolepsy arise are excessive daytime sleepiness and extraordinary. Other symptoms may begin alone or in a combination of months or years after the onset of nap. There are many variations in the development, severity, and sequence of cataplexy appearance, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience have four symptoms. Excessive daytime sleepiness generally lasts throughout life, but sleep paralysis and hypnagogic hallucinations may not occur. Subconscious narcolepsy groups also experience a high taste and aroma known as supertaster phenomena.
Many people with narcolepsy also suffer from insomnia for long periods of time. Excessive sleepiness during the day and katapleksi often become severe enough to cause serious problems in the social, personal, and professional life of a person. Usually, when one is awake, brain waves show a regular rhythm. When a person first falls asleep, brain waves become slower and less regular, called non-rapid eye movement (NREM) sleep. After about one and a half hours of NREM sleep, brain waves begin to show a more active pattern, called REM sleep (rapid eye movement sleep), when the most remembered dreams occur. Associated with EEG waves observed during REM sleep, the muscle atonia present is called REM atonia.
In narcolepsy, the sequence and length of the NREM and REM sleeping periods are impaired, with REM sleep occurring during sleep, rather than after NREM sleep. Also, some aspects of REM sleep that usually only occur during sleep, such as lack of muscle control, sleep paralysis, and a clear dream, occur at other times in people with narcolepsy. For example, lack of muscle control may occur during awake in cataplexy episodes; It is said that there is intrusion of REM atonia during wakefulness. Clear sleep and dream paralysis can occur asleep or awaken. Simply put, the brain does not go through the normal stages of sleep and deep sleep but goes straight into (and out of) rapid eye movement (REM) sleep.
As a result, sleep time does not include deep sleep, so the brain tries to "chase" during the day, then EDS. People with narcolepsy may be seen asleep in unexpected moments (such movements are common). People with narcolepsy fall rapidly into what seems to be sleeping very soundly, and they wake up suddenly and get confused when they do it (dizziness is a common occurrence). They have a very clear dream, which they often remember in great detail. People with narcolepsy may dream even when they just fall asleep for a few seconds. Along with a clear dream, people with narcolepsy are known to have audio or visual hallucinations before falling asleep.
Narcoleptics can gain weight; children can get 20 to 40 pounds (9 to 18 kg) when they first develop narcolepsy; in adults the body mass index is about 15% above average.
Maps Narcolepsy
Cause
The exact cause of narcolepsy is unknown, and may be caused by several different factors. Part of this mechanism involves the loss of orexin-releasing neurons in the lateral hypothalamus. In up to 10% of cases there is a family history of the disorder. There is a strong connection with a particular genetic variant. In addition to genetic factors, low levels of orexin peptides have been correlated with history of infection, diet, contact with toxins such as pesticides, and brain injury from brain tumors or strokes.
Genetics
The main genetic factor that has been heavily involved in the development of narcolepsy involves the area of ​​chromosome 6 known as the human leukocyte antigen complex (HLA). Specific variations in the HLA gene are strongly correlated with the presence of narcolepsy; However, this variation is not necessary for conditions to occur and sometimes occurs in individuals without narcolepsy. Genetic variation in the HLA complex is thought to increase the risk of auto-immune responses to neurons that release orexin in the lateral hypothalamus.
HLA-DQB1 * 06: 02 allele from human genes HLA-DQB1 is reported in more than 90% of patients, and other HLA gene alleles such as HLA-DQA1 * 01: 02 have been attributed. A 2009 study found a strong association with polymorphism in the TRAC gene locus (dbSNP IDs rs1154155, rs12587781, and rs1263646). The review article 2013 reports additional but weaker links to the TNFSF4 gene locus (rs7553711), Cathepsin H (rs34593439), and P2RY11-DNMT1 (rs2305795). Another locus gene that has been associated with narcolepsy is EIF3G (rs3826784).
Vaccines
A link between the GlaxoSmithKline Pandemrix H1N1 flu vaccine and childhood narcolepsy was investigated for an increased prevalence of narcolepsy in Irish, Finnish and Swedish children after vaccination. Finland's National Institute of Health and Welfare recommends that Pandemrix vaccination be suspended pending further investigation into 15 cases of children reported to be narcolepsy. In Finland in mid-November 2010, 37 cases of childhood narcolepsy have been reported by doctors. This can be compared with the normal average of 3 cases of narcolepsy children per year. "The incidence of narcolepsy with cataplexy in children/adolescents in the Swedish population increased during the pandemic period and vaccination, with a rapid decline in incidents during the post-pandemic period." They conclude that these results "provide strong evidence that vaccination with Pandemrix during the pandemic period may be associated with an increased risk of narcolepsy with cataplexy in vulnerable children 19 years and younger." In 2013, the relationship between Pandemrix and narcolepsy was confirmed by a research registry by the Swedish Medical Products Agency, with a threefold increase in risk for people under the age of 20.
Pathophysiology
Orexin, otherwise known as hypocretin, is a neuropeptide acting in the brain to regulate appetite and awake as well as a host of other cognitive and physiological processes. While there are billions of cells in the human brain, only 10,000-20,000 neurons emit orexin peptides; all these neuron projects come out of the lateral hypothalamus. The loss of neurons produces orexin to cause narcolepsy and most individuals with narcolepsy have a reduced number of neurons in their brains.
Nervous control in normal sleep and narcolepsy relations is only partially understood. In humans, narcoleptic sleep is characterized by a sudden tendency to wake up to REM sleep with little or no non-REM sleep. Changes in motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, hyper motor spine and motor stem motorization of alpha motor neurons results in almost complete atony of skeletal muscle via the reticulospinal pathway of descending inhibition. Acetylcholine can be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy has features that are usually only seen in normal REM sleep.
Diagnosis
The diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if sleep attacks are isolated and the cataract is mild or absent, the diagnosis becomes more difficult. There may also be cataplexions in isolation. Three tests commonly used in the diagnosis of narcolepsy are polysomnograms, multiple sleep latency tests (MSLT), and administration of the Epworth Sleepiness Scale. These tests are usually performed by sleep specialists. Polysomnogram involves continuous recording of brainwaves of sleep and a number of nerve and muscle functions during the night's sleep. When tested, people with narcolepsy fall asleep quickly, enter REM sleep early, and may often wake up at night. Polysomnograms also help detect the possibility of other sleep disorders that may cause daytime drowsiness.
Epworth Sleepiness Scale is a brief questionnaire given to determine the possibility of sleep disturbances, including narcolepsy. For some sleep latency tests, a person is given a chance to sleep every 2 hours during normal waking hours. Patients are usually taken for sleeping overnight. The next day the patient will undergo some tests where they will be told to nap after a full night's sleep (usually eight hours). Observations were made from the time required to reach various sleep stages (sleep onset latency). This test measures daytime sleepiness and also detects how fast REM sleep begins. Again, people with narcolepsy fall asleep quickly and enter REM sleep early. Occasionally, some sleep latency tests can produce false-negative for narcolepsy.
The system that regulates sleep, arousal, and transition between these states in humans consists of three interconnected subsystems: orexin projection of the lateral hypothalamus, reticular activation system, and the preoptic ventrolateral nucleus. In narcoleptic individuals, these systems are all associated with disorders due to the large number of hypothalamus ordein projection neurons and significantly fewer orexin neuropeptides in cerebrospinal fluid and nerve tissue, compared with non-narcoleptic individuals. Those with narcolepsy generally experience a REM sleep stage within five minutes of sleep, while people who do not have narcolepsy (unless they lack significant sleep) do not experience REM until after a period of slow-wave sleep, which lasts for about the first hour or so of the sleep cycle.
Measuring the level of orexin in a person's cerebrospinal fluid sampled in a spinal tap may help diagnose narcolepsy, with abnormally low levels acting as an indicator of the disorder. This test can be useful when MSLT results are inconclusive or difficult to interpret.
Classification
The International Sleep Disorder Classification (ICSD) 2001 divides primary hypersomnia syndrome between narcolepsy, idiopathic hypopromia, and recurrent hypersomnia (such as Klein-Levin syndrome); it further divides narcolepsy into it with cataplexy and without cataplexy. This ICSD version defines narcolepsy as an unknown cause disorder "characterized by excessive sleepiness usually associated with cataplexy and other REM-sleep phenomena, such as sleep paralysis and hypnagogic hallucinations." It also sets the basic categorical standard for the diagnosis of narcolepsy, through 2 sets of well-defined criteria, as follows. Narcolepsy diagnostic criteria minimum set # 2:
- A "excessive sleepiness complaints or sudden muscle weakness."
- Related features that include: sleep paralysis; main sleep episodes are disrupted; hypnagogic hallucinations; automatic behavior.
- Polysomnography with one or more of the following: "sleep latency less than 10 minutes;" "REM sleep latency is less than 20 minutes;" an MSLT with an average sleep latency of less than 5 minutes; "two or more REM sleep-onset periods" (SOREMPs).
- "There is no medical or mental distress account for symptoms." (see differential diagnosis of hypersomnia)
In the absence of a clear cataract, it becomes much more difficult to enforce a diagnosis of narcolepsy. "Various terms, such as essential hypersomnia, primary hypersomnia, ambiguous narcolepsy, atypical narcolepsy, etc., have been used to classify these patients, which may be in a narcolepsy developing phase."
Since 2001 ICSD, the classification of primary hypersomnia has steadily evolved, as more research has shown more overlap between narcolepsy and idiopathic hypersomnia. The 3rd edition of ICSD is currently being finalized, and its new classification will be the narcolepsy label caused by lack of orexin as "type 1 narcolepsy," which is almost always associated with cataplexy. Other primary hypersomnia will remain divided according to the presence of SOREMPs. They will be labeled: "type 2 narcolepsy," with 2 or more SOREMPs in MSLT; and "idiopathic hypersomnia", with fewer than 2 SOREMPS.
However, "there is no evidence that pathophysiology or therapeutic response is substantially different for hypersomnia with or without SOREMPs in MSLT." With this overlap of idiopathic and narcolepsy hypersomnia, the 5th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) also renewed the classification of primary hypersomnia. It reclassifies narcolepsy without cataplexy as a major somnolent disorder (MSD). In addition, MSD will include all hypersomnolence syndromes not explained by low orexin concentrations, including idiopathic hypersomnia (with and without long sleep time) and long sleep (people who need 10 hours of sleep/day).
Further complicating this latest classification scheme, the overlap between narcolepsy with katapleksi and idiopathic hypoptomnia has also been reported. A narcolepsy subgroup with a long sleep time, consisting of 18% narcolepsy in one study, has symptoms of narcolepsy with cataplexy and idiopathic hypersomnia (long sleep time and non-recurring naps). It is believed that this subgroup may have dysfunction in various passion systems, including orexin and GABA (see causes of idiopathic hypersomnia).
Treatment
People with narcolepsy can be very helpful, but not cured. Treatment is tailored to the individual, based on therapeutic symptoms and responses. The time required to achieve optimal symptom control varies greatly and may take several months or longer. Drug adjustments are often necessary, and complete symptom control is rarely possible. While oral medication is 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, dextroamphetamine, modafinil, and armodafinil. At the end of 2007, warnings for adverse skin reactions to modafinil were excluded by the FDA.
Other drugs used are atomoxetine, non-stimulant and norepinephrine reuptake inhibitor (NRI), which has no addiction or recreational effects. In many cases, short naps planned may reduce the need for pharmacological treatment of EDS, but only improve symptoms for short duration. A 120-minute nap provides benefits for 3 hours in patient alertness while a 15-minute nap provides no benefit. Sleeping during the day is not a substitute for a night's sleep. Ongoing communication between health care providers, patients, and family members of patients is essential for optimal narcolepsy management.
Another FDA-approved treatment option for narcolepsy is sodium oxybate, also known as sodium gamma-hydroxybutyrate (GHB). It can be used for cataplexy associated with narcolepsy and excessive daytime sleep associated with narcolepsy.
Narcolepsy is sometimes treated with selective serotonin reuptake inhibitors and tricyclic antidepressants, such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep. Venlafaxine, an antidepressant that blocks reuptake of serotonin and norepinephrine, has demonstrated usefulness in managing the cataplexy symptoms; however, it has side effects including sleep disturbances.
Epidemiology
In the United States, it is estimated that this affects over 200,000 Americans, but fewer than 50,000 are diagnosed. It is widespread such as Parkinson's disease or multiple sclerosis and is more common than cystic fibrosis, but is less known. Narcolepsy is often misinterpreted as depression, epilepsy, or side effects of drugs. It can also be misinterpreted as bad sleep habits, drug use, or laziness. Narcolepsy can occur in men and women at any age, although symptoms are usually first seen in adolescents or young adults. There is strong evidence that narcolepsy can occur in families; about 10 percent of people diagnosed with narcolepsy with cataplexy have close relatives with this neurological disorder. While the symptoms of narcolepsy are often confused with depression, there is a relationship between two disorders. Research studies have mixed results on co-occurrence of depression in narcolepsy patients - numbers cited by different studies anywhere between 6% and 50%.
Narcolepsy has a distinct onset in adolescence and young adulthood. There is an average 15 year delay between correct onset and diagnosis that can contribute substantially to the crippling features of the disorder. The cognitive, educational, occupational, and psychosocial problems associated with excessive daytime narcolepsy dentures have been documented. For this to happen in crucial teenage years when education, self-image development, and job-choice development are ongoing is devastating. While cognitive impairment does not occur, it may simply be a reflection of excessive daylight somnolen.
The prevalence of narcolepsy is about 1 per 2,000 people. This is the reason for the patient's visit to the sleep disturbance center, and with the onset of adolescence, it is also a major cause of learning difficulties and absenteeism from school. Normal adolescents often experience excessive daytime sleepiness due to increased physiological sleeping tendencies worsening due to educational and social pressures; this may be crippling with the addition of narcolepsy symptoms to vulnerable 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 shortage in the controlled double-blind study literature for the possibility of an effective drug or other form of therapy. The mechanism of action of several available therapeutic agents has been explored but a detailed study of the mechanism of action is required before a new class of therapeutic agents can be developed. Narcolepsy is an undiagnosed condition in the general population. This is partly because the severity of the severity varies, so it can be misunderstood with other diseases very easily. Some people with narcolepsy do not suffer from muscle loss.
Society and culture
In 2015, it was reported that the UK Department of Health paid for sodium oxybate drugs at a cost of £ 12,000 per year for 80 people taking legal action on issues related to the use of the Pandemrix swine flu vaccine. Sodium oxybate is not available for people with narcolepsy through the National Health Service.
Research
Histopathically-directed drugs
"Based on the role of histamine in keeping people awake (and hence the common anti-histamine side effects such as diphenhydramine cause drowsiness), drugs acting on histamine are under development for excessive sleepiness." It remains to be seen whether this H3 antagonist (ie, a compound such as pyrolysine promoting the build-up histamine release) would be useful as a build-up agent.
Drug-directed GABA
Given the possibility of the role of hyponactive receptor GABA A on primary hypersomnia (narcolepsy and idiopathic hypopromia), drugs that can counteract this activity are being studied to test their potential for increased drowsiness. These currently include clarithromycin and flumazenil.
Flumazenil
Flumazenil is the only GABA receptor antagonist A in the market in January 2013, and is currently only produced as an intravenous formulation. Given pharmacology, researchers consider it as a promising drug in the treatment of primary hypersomnia. Results from a small, double-blind, randomized, controlled clinical trial were published in November 2012. The study showed that flumazenil provided relief for most patients whose CSF contained an unknown "somnogen" that improved the function of GABA A receptors, making them more susceptible to the sleep-inducing effect of GABA. For one patient, daily administration of flumazenil with sublingual candy and topical creams has proven effective for several years. The 2014 case report also shows improvement in symptoms of primary hypersomnia after treatment with continuous subcutaneous flumazenil infusion. The generic flumazenil supply was initially considered too low to meet the potential demand for treatment of primary hypersomnia. However, this scarcity has been reduced, and dozens of patients are now treated with flumazenil outside the label.
Clarithromycin
In the test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to restore the functioning of the GABA system to normal in patients with primary hypersomnia. Therefore, the researchers treated some patients with unlabeled clarithromycin, and most felt their symptoms improved with this treatment. To help further determine whether clarithromycin is really beneficial for the treatment of narcolepsy and idiopathic hypersomnia, randomized, small, double-blind, controlled clinical trials completed in 2012. "In this pilot study, clarithromycin enhances subjective sleepiness in GABA-associated hypersomnia. Larger trials with longer durations are guaranteed. "In 2013, a retrospective review evaluating the long-term use of clarithromycin showed efficacy in a large percentage of patients with GABA-related hypersomnia. "It is important to note that the positive effects of clarithromycin are secondary to antagonistic effects such as benzodiazepines, not their antibiotic effects, and care should be taken care of."
Orexin receptor agonists
Orexin-A ( a.k.a. hypocretin-1) has been shown to be very awakening to animal models, but unfortunately does not cross the blood-brain barrier. Therefore, companies have developed orexin receptor antagonists, such as suvorexant, for the treatment of insomnia. It is also possible that the orexin-A receptor agonist will be discovered and developed for the treatment of hypersomnia.
L-carnitine
Very low acylcarnitine levels have been observed in people with narcolepsy. This same low rate has been associated with primary hypersomnia in general in rat studies. "Mice with systemic carnitine deficiency exhibit higher frequencies of disseminated wake and rapid eye movement (REM) sleep, and reduced locomotor activity." Administration of acetyl-L-carnitine was shown to improve this symptom in mice. Subsequent human trials found that narcolepsy patients who were given L-carnitine spent less total time in daytime sleep than patients who were given a placebo.
References
Source
- Mitler MM, Hajdukovic R; Hajdukovic (June 1991). "Relative Efficacy of Drugs for the Treatment of Sleepiness in Narcolepsy". Sleep . 14 (3): 218-20. PMC 2246380 . PMIDÃ,1680245
- Chabas D, Taheri S, Renier C, Mignot E; Taheri; Renier; Mignot (October 2003). "Narcolepsy Genetics". Annual Review of Genomics and Human Genetics . 4 : 459-83. doi: 10.1146/annurev.genom.4.070802.110432. PMID 14527309. CS1 maint: Many names: list of authors (links) Smith, Jackson MW, Neufing P, McEvoy RD, Gordon TP; Jackson; Neufing; McEvoy; Gordon (2004). "Autoantibody functional in narcolepsy". Lancet . 364 (9451): 2122-4. doi: 10.1016/S0140-6736 (04) 17553-3. PMIDÃ, 15589310 CS1 maint: Many names: list of authors (links)
External links
- "Halaman Informasi Narkolepsi". National Institute of Neurological Disorders dan Stroke.
- Narcolepsy UK
Source of the article : Wikipedia
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