Narcolepsy

from Wikipedia, the free encyclopedia
Classification according to ICD-10
G47.4 Narcolepsy and cataplexy
ICD-10 online (WHO version 2019)

The narcolepsy is a hypersomnia from central nervous system unrelated to sleep-disordered breathing. It belongs to the group of sleep addictions , as it is based on a disruption of sleep-wake regulation. In the vernacular, the disease is therefore also known as "sleeping sickness" or "slumber addiction".

A distinction is made between narcolepsy with cataplexy ("classic narcolepsy"), narcolepsy without cataplexy ("monosymptomatic narcolepsy") and secondary narcolepsy (including structural lesions of the hypothalamus or upper brain stem in ischemia , tumor or neurosarcoidosis ).

The classic narcolepsy is a neurological disease and the main symptoms excessive daytime sleepiness and cataplexy characterized. The wakefulness, NREM and REM sleep and their transitions with correspondingly complex symptoms are affected . First noticeable are the attacks of falling asleep , which are irresistible for those affected and which can occur in the context of excessive daytime sleepiness during the day. Furthermore, a partial or complete loss of muscle tension can occur in the cataplexy and thus cause falls. This loss of tone occurs when fully conscious and is triggered by strong emotions.

Often the night sleep is not restful due to persistent sleep disorders, so that in addition to sleepiness in the sense of a tendency to fall asleep, there is also a lack of sleep . Current studies investigate the consequences of chronic sleep deprivation in narcolepsy patients and its effects on metabolism and body weight .

distribution

According to estimates by the German Society for Sleep Medicine (DGSM), around 40,000 people in Germany suffer from this disease ( prevalence : approx. 26–50 / 100,000 with a high number of unreported cases). According to the researcher Geert Mayer, around 4,000 people have been diagnosed with it .

Course of disease

With regard to the first appearance of the symptoms, there is an average value around the age of 25 with an accumulation around the age of 15 and around 35; but the disease can occur at any age. Children are also affected. However, the first clinical symptoms rarely appear before puberty.

With increasing age, the symptoms usually shift from cataplectic phenomena in adolescence to an increased urge to sleep in advanced age. However, exact epidemiological studies are lacking.

Causes of Narcolepsy

Investigations from 2004 indicated a loss of the hypocretin formed in the hypothalamus , which influences sleep, eating, emotional and reward behavior. It was not until 2018 that a Swiss research team found out using blood tests in narcoleptics that T lymphocytes of the subtype CD4 (in some cases also of the subtype CD8) react to hypocretin. These T cells cause inflammation that destroys neurons that are responsible for producing hypocretin. The combination of the HLA allele DQB1 * 0602 haplotype and environmental factors such as certain infections or vaccines must be present. The exact mechanism that leads to the destruction of those neurons is so far unknown.

In addition to humans, the disease has also affected dog breeds since 1973, e.g. B. Doberman and Labrador known. A research group at Stanford University in the United States claims that a mutation in the hypocretin-2 receptor is the cause of narcolepsy in dogs. In parallel, it was stated that the disease is phenotypically analogous to humans and dogs due to deletion of the prepro-hypocretin gene in mice. People with narcolepsy have either no or very low levels of hypocretin in the brain. In the meantime, the names of the neuropeptides hypocretin- 1 and hypocretin-2 are no longer used as often, instead the names orexin-1 and orexin-2, respectively. Narcolepsy has very high associations with some HLA alleles. A hereditary component is therefore being discussed in research, as around 88–98% of patients with cataplexies carry the allele HLA-DQB1 * 0602 (ie have a certain blood factor on the leukocytes that only affects around 25% of all people in the general population is found). Other HLA alleles also correspond to narcolepsy (DRB1 * 1501, DRB5 * 0101, DQA1 * 0102), but with a lower frequency. The blood factor itself does not seem to be the cause. Rather, its gene locus is probably very close to that of the gene of the hypothetical cause of narcolepsy. HLA-DQB1 * 0301 is found more frequently in HLA-DQB1 * 0602-negative patients. This correlates with an accumulation of partial symptoms of narcolepsy in family members of the sick.

HLA-DR15 was tested for until the end of the 1990s, with the specificity being subject to great ethnic variations. African Americans have this blood factor to about 60%, Japanese to almost 100%.

Some cases of narcolepsy appear to have been caused by the swine flu vaccination . With 31 million doses of the vaccine administered worldwide (as of January / February 2011), hundreds of cases of narcolepsy in connection with the Pandemrix vaccination have occurred, especially in children and adolescents aged 4 to 19 years. In Sweden, where at the end of 2009 60% of the population had been vaccinated after a vaccination appeal by the government, there were several hundred suspected cases, of which around 300 were recognized. There are around 80 suspected cases in Germany. Molecular mimicry is probably the cause of the disease , as the vaccine can be mistaken for the neurotransmitter hypocretin if there is a genetic predisposition . This then upsets the sleep rhythm in the brain and causes narcolepsy.

Symptoms

According to the clinical symptoms, the work of Yoss and Daily coined the term narcoleptic tetrad . This stands for the combination of

  1. excessive daytime sleepiness,
  2. Cataplexies ,
  3. Sleep paralysis and
  4. hypnagogic hallucinations .

Excessive daytime sleepiness occurs in around 95% of patients, cataplexy in around 90% of patients, sleep paralysis in around 40 to 50% of patients, and hypnagogic and hypnopompic hallucinations in around 40 to 50% of patients. However, all four symptoms of the full tetrad affect only 15 to 30% of patients.

In addition, other symptoms such as disturbed night sleep with many interruptions and long waking times and automatic actions and side effects such as an increased BMI and, as a result of daytime sleepiness, memory and concentration disorders can occur.

The symptoms vary greatly from person to person. Hardly any narcoleptic shows all symptoms in their full expression; narcolepsy is subject to large individual fluctuations in its expression between the various symptoms. In most cases, minor manifestations of the other symptoms can only be detected with very detailed examinations. It is difficult to diagnose narcolepsy without cataplexies because it is difficult to distinguish from other hypersomnias. The inconsistent symptoms are likely to be the reason for a small number of confirmed diagnoses and a high suspected number of unreported cases.

In addition, narcoleptics have an increasing number of other sleep disorders such as non-REM and REM parasomnias , restless legs syndrome and sleep-related breathing disorders.

Around 70% of those affected state that they cannot sleep through the night on a regular basis, and around 30% get up to eat something or do other activities. Movement during sleep and the associated arousals contribute to the fragmentation of sleep in patients with narcolepsy with cataplexy. In both REM sleep and NREM sleep, there are more and longer lasting movements that also involve more regions of the body.

Excessive daytime sleepiness

The symptom of drowsiness , often called excessive daytime sleepiness because of its severity, must be differentiated from fatigue in the sense of too little sleep . Despite getting enough sleep, there is a tendency to fall asleep all day. Daytime sleepiness changes in a circadian rhythm and depending on monotony .

The constant feeling of sleepiness leads to sleep when the opportunity arises, even in situations in which a healthy person would not fall asleep.

In addition, certain monotonous situations (such as train journeys, lectures) trigger irresistibly sudden falling asleep, also called imperative sleep attacks, in some affected persons. The duration of sleep is usually between a few seconds and about 20 minutes during attacks. Harbinger symptoms such as double vision only occur in some patients. Episodes of unwanted falling asleep can repeat themselves several times a day, are mostly perceived as relaxing, but limit the performance and social life of those affected.

According to the ICSD, three degrees of severity are differentiated for drowsiness . Criteria are the frequency of unintentional falling asleep episodes, the level of activity when it occurs and the level of attention appropriate to the situation, as well as the effects. In addition, the expected results in the multiple sleep latency test are listed. The degree of mild sleepiness stands for episodes of falling asleep in phases of rest and in passive situations (such as watching TV, as a passenger in the car) that do not necessarily occur daily and hardly limit the person concerned. Moderate sleepiness is assumed to be the case with daily falling asleep with little physical activity in situations that require a minimum level of attention, including in public (such as attending concerts, listening to lectures or working meetings). The social or professional function is impaired. Of severe sleepiness is in daily falling asleep in active situations (such as while eating, driving records, while walking, in direct conversation with a counterpart) to go out. The social or professional impairments are considerable. If you are very sleepy, there is a greatly increased risk of accidents and injuries.

Daytime sleepiness is often the first symptom to appear in isolation.

Cataplexy

Under cataplexy means the affectively triggered, sudden and temporary loss of control ( loss of tone ) over the postural muscles without consciousness. The facial muscles and bilaterally the neck and knee muscles are most frequently affected. However, smooth muscles , respiratory muscles, and tongue and throat muscles are never involved. Developments can be observed, from the brief relaxation of facial expressions to slurred speech, dropping objects, buckling in the knees and even complete falls. The state lasts a few seconds and ends suddenly. A duration of up to half an hour occurs, a duration of hours and longer is observed when anti- cataplectic medication is suddenly stopped and is called status cataplecticus . The frequency varies considerably and depending on the affective triggers. These affective triggers include joy, laughter, shame, excitement, anger, arousal or shock, more generally strong emotions . If laughter is the trigger, it is also referred to as laughing slap .

Abnormal sleep patterns

The third group of symptoms consists of an abnormal sleep rhythm (for example, four hours awake, four hours of sleep, and so on during the day and night), as well as in shifted REM phases (dream sleep phases), which atypically precede dreamless sleep. As a result, waking and dreaming images can be mixed up when falling asleep and lead to so-called hypnagogic (preceding sleep) hallucinations.

Nocturnal sleep is disturbed even if the person concerned adheres to the usual bed rhythm. Nocturnal sleep profiles show a torn, fragmented sleep, which only partially reveals the normal 90-minute sleep cycles in healthy people. It is noticeable that no uniform pattern can be recognized over several nights and that the REM phases untypically precede the dreamless sleep phase (NO-REM). Those affected often feel that their sleep is not very relaxing.

In healthy people, the approximately 90-minute activity rhythm of the sleep phases persists even during the waking period as a rhythm of changing mental and physical performance. Correspondingly, this regularity breaks down in narcoleptics during the waking phase. This may be the link to increased daytime sleepiness in most narcolepsy patients.

Sleep paralysis

In the sleep paralysis , also called sleep paralysis, it is initially a natural process of sleep stage REM sleep , whose task is the implementation of dream content to avoid in real muscle movements. Sleep paralysis is usually not experienced consciously because it ends without delay when you wake up.

If the sleep-wake regulation is disturbed, the lines between sleep and wakefulness blur. There is a dissociation of the states of sleep and wake , which are otherwise exactly separated. As a result, sleep paralysis, which is actually linked to a sleep phase, can occur at the transition from being awake to sleeping (hypnagogic form, i.e. switched on too early ) or at the transition from sleeping to being awake (hypnopompe form, i.e. switched off too late ) and leading to a temporary inability to perform movements speak or even get up willingly, lead. The condition occurs preferentially in the supine position.

As in REM sleep, muscle atony also affects the auxiliary breathing muscles. The diaphragm and eye muscles are not affected. Sleep paralysis is not vitally threatening, although the feeling of shortness of breath and the heaviness on the chest are frightening. The affected person perceives his surroundings, but can hardly make himself noticeable.

The condition usually lasts a few minutes and ends spontaneously. External triggers such as touch can end sleep paralysis earlier. The repeated occurrence in series is possible. The symptom is not tied to night sleep, but can also occur before or after additional sleep episodes of the symptom of excessive daytime sleepiness .

Especially in the first time, these episodes will have a frightening effect on the person affected, which is made even more difficult by the hallucinations that often occur. Without appropriate information, those affected are also concerned that a mental illness is present or could be suspected, which can lead to the silence of the symptom and thus to further stress.

As coping strategies avoiding the supine position and concentrating on trying to come to move during the state a body part or roll their eyes or to alert the partners by groans that can redeem those affected simply by touching from the state into consideration. There is no specific drug treatment for this symptom associated with REM sleep; it is treated together with hallucinations and cataplexies.

Sleep paralysis is not a symptom specific to narcolepsy. Isolated sleep paralysis can occur sporadically (in around six percent of the population at least once in a lifetime) or with familial accumulation even without narcolepsy.

Hypnagogic hallucinations

Like sleep paralysis, the symptom can occur both when falling asleep (hypnagogic form and thus included in the narcoleptic tetrad ) and when waking up (hypnopompe form). The hallucinations are predominantly visual, but also occur tactile or auditory and express themselves as often complex and extremely realistic illusions and dreams (people in film-like scenes, body schema disorders). After the episode, those affected manage to classify the content as unreal.

These hallucinations are not tied to night sleep, but can also occur before or after additional sleep episodes of the symptom of excessive daytime sleepiness or in connection with cataplexy. With regard to the effect of these hallucinations on those affected, who experience it as very realistic, and their fears and fears, the description under sleep paralysis applies .

There is no specific drug treatment for this symptom associated with REM sleep; it is treated together with sleep paralysis and cataplexy.

Sleep-related hallucinations are not a symptom specific to narcolepsy.

Automatic behavior

The automatic behavior belongs to the NREM -associated and unspecific symptoms, but is included in the diagnostic criteria of the ICSD. In the case of automatic behavior, an action (such as writing, driving a car, cooking) is stereotypically continued in a sleep-like state . The reaction to external stimuli is delayed, perception, memory and continuous performance are impaired and the result is often faulty. During this time there is a greatly increased risk of accidents. Severe drowsiness and lack of opportunity to sleep encourage the occurrence of automatic behavior.

Automatic behavior is observed in about 20% of narcolepsy patients.

Diagnosis

Diagnostic measures include a targeted recording of the medical history ( anamnesis ) by the doctor, documentation using various questionnaires (such as the Epworth Sleepiness Scale (ESS)) and sleep diaries as well as examinations using polysomnography and multiple sleep latency tests (MSLT). In individual cases, the orexin level in the cerebral fluid or HLA typing can be carried out, which is particularly recommended if the differential diagnosis is unclear.

In MSLT, a shortened sleep latency of less than 8 minutes and an early occurrence of REM sleep ( sleep-onset-REM , SOREMP), which can be observed in at least two cases , are expected after five sessions. However, about 20% of the patients do not show a double SOREM, so they are recognized as "false negative". SOREM is also found in healthy people.

In the evaluation of the MSLT with regard to sleep latency and SOREMP, around 15% of narcoleptics with cataplexy show a normal or borderline result, in older patients (from 36 years of age) it is even around 25%.

treatment

Narcolepsy is according to current knowledge, a life-long-lasting disease with a 1.5-fold increased mortality rate ( mortality ) against people without narcolepsy. The individual symptoms occur per patient and in the course of the disease with variable intensity. The treatment depends on the dominant symptoms and the impairments caused by them. According to the "Guideline S 2 - Non-restful sleep" of the German Society for Sleep Research and Sleep Medicine (DGSM) , non-drug coping strategies are rarely sufficient to adequately suppress symptoms. Therefore, drug treatment is usually also required. Daytime sleepiness is counteracted with stimulants (e.g. methylphenidate ), while antidepressants are used against cataplexy, hallucinations and sleep paralysis.

Behavioral measures

According to the guidelines of the German Society for Neurology (DGN), the following behavior-modifying measures can be considered as non-drug measures:

  • Coping strategies , d. H. Establishment of life processes according to the specific symptom characteristics (e.g. avoidance of trigger situations for cataplexies or forced sleep)
  • Sleep hygiene
  • Individually adapted daytime sleep episodes

Medication

Currently are in Germany Modafinil , methylphenidate sodium oxybate (, 4-hydroxybutyric acid , sodium salt) clomipramine approved and since 2020 Solriamfetol for the treatment of narcolepsy. In 2005, sodium oxybate was approved across the European Union for the treatment of cataplexy in adult patients with narcolepsy.

Daytime sleepiness can be partially alleviated by active ingredients such as Modafinil (1st choice) or methylphenidate (2nd choice). Cataplexy, sleep paralysis, and hallucinations should be addressed first with sodium oxybate or clomipramine. Sodium oxybate is a sleep aid that begins to show detectable effects after at least two weeks of use. It is also said to have a beneficial effect on daytime sleepiness.

Depending on the individual response of the patient, tricyclic antidepressants or serotonin reuptake inhibitors such as B. fluoxetine are treated. The latter, however, are not approved for narcolepsy. Other substances that can be used off-label against daytime sleepiness include: a. Fenetylline , Dextroamphetamine , Methamphetamine , Amphetaminil , Fencamfamine , Mazindol , Selegiline , Phenelzine , Ritanserin, Caffeine and L-Dopa .

Narcolepsy in the social environment

The problem for the sick is the fact that, despite the spectacular symptoms in some cases and the level of suffering as a person affected, a considerable amount of time often passes between the appearance of the symptoms and the first doctor's visit until the correct diagnosis - if it is made. In Germany, the Federal Statistical Office assumed a duration of more than ten years for this in 2005 .

Studies in other countries also confirm the often long ordeal of those affected. In North America, a 1997 study found an astonishing 16 years mean. In the year before narcolepsy was correctly diagnosed, a large number of other psychological and neurological disorders such as forms of depression , personality disorders and epilepsy were diagnosed and treated in patients according to a study in Canada , which indicates the coexistence of these diseases or a considerable number of incorrect diagnoses .

If not adequately cared for, the disease causes high social costs, for example due to accidents, in addition to the suffering that those affected do not achieve private, social, school and professional goals; Sick leave and early retirement are further consequences. The investigation of the quality of life in narcolepsy patients in Norway using the SF-36 questionnaire showed consistently worse results than in the control group , except for the domain vitality . Particular attention should be paid to the areas of social functioning and general health perception of the patient.

Narcolepsy is not associated with a mental disorder or mental underperformance . The patients remain mentally normal, but are often defamed as sleepyheads, simulators or lazy people.

The problems in the daily routine can also lead to depression and / or social phobia . Those affected pull themselves out of shame or fear of injury and the like. U. back and have fewer social contacts as a result. It is important that the person's immediate environment accepts the illness and takes it into account. This also includes the acceptance of sleep breaks, low activity and the like. Ä.

The patient's situation can be made considerably easier by the allocation of a suitable workplace where he can cope better with his disorder. Depending on the individual manifestation of the symptoms, e.g. B. Office work instead of work on moving machines, when cataplexy could lead to fatal operating errors. In other known cases, certain office activities (e.g. screen monitoring) trigger a forced sleep attack, which is then particularly unacceptable in customer traffic. Narcolepsy can reduce the ability to work up to the point of total disability.

Narcolepsy can severely reduce the quality of life and the ability to work. With regard to the severely disabled status , the Annex to Section 2 of the Medical Care Ordinance applies in Germany . Then, depending on the frequency, severity and combination of symptoms (daytime sleepiness, sleep attacks, cataplexies , automatic behavior in the context of symptoms of fatigue, sleep paralysis - often associated with hypnagogic hallucinations), a GdB of 50 to 80 should generally be set. Depending on the severity of the symptoms, the marks G and B come into consideration. Medical reviewers should have knowledge and experience in sleep medicine. If several diseases with the main symptom hypersomnia (for example sleep apnea syndrome or restless legs syndrome ) exist at the same time, the reduction in performance must be taken into account according to the intensification of the main symptom.

history

The first case descriptions of narcolepsy were given in 1877 by the German doctor Carl Westphal from Berlin (as part of a lecture at the Berlin Medical-Psychological Society), and shortly afterwards in February 1878 by Franz Fischer from Pforzheim. Both authors found a link between sleep attacks and muscle weakness that was triggered by emotions. In 1880, the French doctor Jean-Baptiste-Edouard Gélineau first used the term narcolepsy (Greek: nárkōsis = put to sleep, lêpsis = attack) in his publication “From narcolepsy”. An English translation of the original Gélineau article was published in 2007 by Carlos Schenck. The cataplexy as another symptom of narcolepsy was first 1902 by Leopold Loewenfeld described. In 1935, the American doctors Prinzmetal and Bloomberg published the possibility of treating narcolepsy with amphetamine (amphetamine) because it has a stimulating effect on the central nervous system. Yoss and Daly coined the term narcoleptic tetrad and discovered in 1957 in the EEG of narcolepsy patients peculiarities when alternating between waking and sleeping phases. Methylphenidate ( Ritalin ) has been used in the treatment of narcolepsy since the early 1960s .

See also

literature

  • Nils Birbaumer, Robert F. Schmidt: Biological Psychology. 6th edition. Springer, Heidelberg 2006, ISBN 3-540-25460-9 , p. 535 ff. (Chapter: Circadian Periods, Sleep and Dream )
  • Geert Mayer: Narcolepsy. Genetics - Immunogenetics - Motor disorders . Blackwell, Berlin 2000, ISBN 3-89412-449-0 . (Basic work)
  • Geert Mayer: Narcolepsy. Pocket atlas special . Thieme, Stuttgart 2006, ISBN 3-13-134431-8 .
  • Geert Mayer, Thomas Pollmächer (ed.): Narcolepsy. New opportunities in diagnostics & therapy . Thieme, Stuttgart 2007, DNB 983822816 .
  • Peter Geisler u. a .: Narcolepsy: information for patients, relatives and doctors , German Narcolepsy Society e. V., DNG, Kassel 2005, DNB 979070856 .
  • Susanne Schäfer: The "sleeping sickness" narcolepsy. An experience report about laughing, paralysis and sleeping in cardboard boxes . Free Spiritual Life Publishing House, Stuttgart 1998, ISBN 3-7725-1744-7 .
  • Susanne Schäfer : Narcolepsy in Childhood . German Narcolepsy Society, Kassel 2001, DNB 97908024X .
  • Georg Handwerker: Narcolepsy - daytime sleepiness in children. In: Monthly for Pediatrics. 155th year 2007, pp. 624-629.
  • EFNS guidelines on management of narcolepsy . Blackwell Publishing, Reprint, Vol. 12, No. 10, October 2006.
  • S1 guideline narcolepsy of the German Society for Neurology (DGN). In: AWMF online (as of 2012)
  • Geert Mayer u. a .: Narcolepsy: diagnosis and therapy . In: Deutsches Ärzteblatt , Heft 5, 2001, 98, pp. A249 – A254

Web links

Wiktionary: Narcolepsy  - explanations of meanings, word origins, synonyms, translations

Individual evidence

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