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

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?

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

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.

Expert com­ment

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.

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