This strange disease was first described in 1880 by the French physician Jean-Baptiste Gelino. And for a hundred years, the cause of narcolepsy remained a mystery. About what this disease is, how it manifests itself, and whether it can be treated, read the MedAboutMe article.
Narcolepsy is not about drugs
Although many people think so when they hear something about “narcos” in the title. Others hear similarities with epilepsy, but this is also a mistake. Narcolepsy is not related to either drug addiction or epilepsy, although the latter can sometimes be somewhat similar.
Still sometimes a person with narcolepsy is considered a pathological lazy person, because he can be overcome by constant drowsiness. And already an hour after a normal night’s sleep, the poor fellow can naturally turn off, falling into an irresistible sleep.
And if narcolepsy is also accompanied by cataplexy, then others may be frightened. Is it a joke — a person can suddenly fall on the go, while talking or laughing. And not be able to get up, because his body ceases to obey. I don’t even have the strength to move my hand.
Seeing a doctor may not work, because not all doctors know about narcolepsy. And they usually refer the patient to various examinations and tests that do not reveal anything special. In half of patients, narcolepsy first manifests itself at the age of 15, and complaints are often not taken seriously.
The problem is that narcolepsy is a rare disease. For different countries, medical statistics give different figures: from 1 case per 500 thousand people in Israel, 1 per 1000 people in the United States to 1 out of 600 people in Japan. Many doctors may never encounter this disease during their entire professional career, as a result of which they are not sufficiently aware of diagnostic methods. In Russia, narcolepsy is not included in the MHI, and it is very difficult to “knock out” a referral for the necessary examination, and not everyone can afford it on a paid basis. In addition, the base for the examination is also available only in some medical and scientific institutions.
However, for some time now it has become possible to establish the correct diagnosis, since in 1989 a discovery was made that finally made it possible to understand the cause of the development of narcolepsy.
Orexins, they are hypocretins
At the very end of the 1980s, two groups of researchers simultaneously found and isolated previously unknown proteins, called hypocretins by some of the discoverers, and orexins by others. Orexin neurons, whose neurotransmitters are orexins/hypocretins, are rather few and are located in the hypothalamus. But they are associated with almost all parts of the brain, and can affect different processes.
It was found that the lack of orexins is the cause of the development of narcolepsy. It also affects eating behavior, fat metabolism and energy balance, glucose levels, insulin sensitivity, and the level of the “satiety hormone” leptin. And orexins play one of the central roles in the mechanism of the formation of addiction and dependence. Including drugs.
Narcolepsy can be associated with both low levels of orexins and the absence of orexin neurons. The result of this deficit is a violation of the normal balance between the phases of “REM” and “slow” sleep. During sleep, a person does not get enough sleep, and during the daytime, REM sleep can suddenly “break in” into the wakefulness mode, forcing a person to “turn off” on the go or while performing any actions.
What is the cause of hypocretin deficiency? Studies show that it is most likely associated with autoimmune disorders, that is, the body itself attacks its own neurons.
Where do orexins go?
Yes, experts will forgive, but for a more understandable presentation, both the terminology and the picture of what is happening will have to be extremely simplified.
T‑cells of various types are at the front line of the body’s defense against all sorts of enemies. It is they who are able to recognize “strangers” by certain fragments of protein molecules, and attack them. How do T cells know that these particular fragments are the “keys to the portrait” of strangers? And this is what they are told by the so-called HLA proteins, which are found in every cell. And, if something pathological has started in the cell, the HLA protein “pokes” out, beyond the cell membrane, a fragment of the “enemy” molecule. The T‑cell “sees” the fragment, recognizes it as a signal of an enemy attack, and responds with all the “proletarian hatred”.
But sometimes the HLA proteins go crazy and start showing fragments of the most normal, common and natural proteins for the body to T cells. What about T cells? They “see” that the HLA protein “waves” something out of the cell, which means that this “something” is an enemy. Which needs to be destroyed.
So: it turned out that in the blood of patients with narcolepsy there are antibodies against neurons, and also in most of them “broken” versions of the HLA gene are found in the genome. And among the T‑cells in the patient’s blood there are those in whose memory the orexin molecules are recorded as an “image of the enemy”. This means that the deficiency of orexins and the loss of orexin neurons is a consequence of an autoimmune process.
At the same time, there are people who also have a defective gene for HLA proteins in their genome, but their immunity does not perceive orexins as “enemy proteins”. And how T cells respond to hypocretins may depend on both their type and the type of HLA proteins. In general, the picture is complex and confusing, but as far as the functioning of the immune system is concerned, this is a common thing.
The main thing is that the causes of the disease have become more understandable, diagnostic methods are being developed and ways of treatment have been outlined.
Diagnosis and treatment of narcolepsy
The basis for suspicion is the information reported by a person suffering from sleep disorders. Instead of smooth falling asleep and awakening, episodes of spontaneous sleep / imperative drowsiness, abrupt awakening appear, during which hallucinations, sleep paralysis, and a sharp decrease in muscle tone may occur. During sleep, vivid, realistic dreams are more likely to occur. During the day, a manifestation of cataplexy is possible, that is, loss of muscle tone, partial or complete. A person can suddenly fall, for example, during strong laughter, from strong emotions, and this can also happen in those places and situations where a fall is dangerous to life and health. For example, on the stairs, at the subway station, while swimming.
Cataplexy is more likely to occur when orexin deficiency is associated with loss of orexin neurons.
Memory lapses may occur, but often the patient, even during an attack of cataplexy, is conscious, aware of and remembers everything.
The main diagnostic method is polysomnography, as well as a set of tests to maintain alertness and sleep latency tests. A cerebrospinal fluid test for hypocretin levels may also be performed.
The doctor determines the tactics of treatment. One of the methods is hypocretin replacement therapy, it is also possible to administer immunoglobulins, take antidepressants, etc. The use of psychostimulants gives a good result, but they are prohibited in our country for use, since they cause dependence in everyone except for patients with narcolepsy. Unfortunately, most of the main drugs used to treat narcolepsy abroad are not registered in Russia or are on the banned list.
Thomas Scammel, Professor of Neurology at Harvard Medical School
Narcolepsy is a fairly rare brain disease in which there is a malfunction or loss of hypocretin neurons in the hypothalamus. Type 1 narcolepsy is characterized by severe daytime sleepiness, sometimes irresistible, cataplexy, that is, a sudden loss of muscle tone, and there may also be sleep paralysis, hallucinations when falling asleep or waking up. Changes in motor, mental, emotional, cognitive, metabolic and vegetative functions are also not excluded.
Narcolepsy type 2 is more typical of just daytime sleepiness. The second type can pass into the first.
Until recently, the diagnosis of narcolepsy was difficult, as a result of which the patient could receive improper treatment for years. This is the problem with many rare diseases. However, today a diagnostic technique has been developed that makes it possible to identify the disease and select an adequate treatment.
For other causes of sleep problems, read the article Sleep Disorders — Causes and Treatment.