Sleep disorders

Sleep is a special genetically determined state of the organism of warm-blooded animals (i.e. mammals and birds), characterized by a regular sequential change of certain polygraphic pictures in the form of cycles, phases and stages. In this definition, attention should be paid to three supporting points: firstly, the presence of sleep is genetically predetermined, secondly, the structure of sleep is most perfect in higher species of the animal world and, thirdly, sleep must be recorded objectively.

Modern somnology is one of the most dynamically developing areas of modern medicine. Objective sleep research - polysomnography - originates from the works of H. Berger (1928) on EEG recording, which made it possible to identify regular EEG changes during sleep. The next stage in the development of somnology was the description of the rapid eye movement (REM) phase by E. Aserinsky and N. Kleitman in 1953. Since then, the minimum set of studies absolutely necessary for assessing the stages and phases of sleep include EEG, electrooculogram (EOG) and EMG. Another important stage in development was the creation of the "bible" of modern somnology: the manual of A. Rechtchaffen and A. Kales (A manual of standardized terminology, techniques and scoring for sleep stages of human subjects. - Bethesda, Washington DC, US Government Printing office, 1968), which made it possible to largely unify and standardize the methodology for decoding a polysomnogram.

Currently, the following diseases and conditions are actively studied within the framework of somnology: insomnia, hypersomnia, sleep apnea syndrome and other sleep-disordered breathing, restless legs syndrome, periodic limb movements and other movement disorders during sleep, parasomnia, epilepsy, etc. The list of these areas shows that we are talking about very common problems that are of great importance for modern medicine. Naturally, the diagnostic capabilities of EEG, EMG, electrooculogram are not enough to study such a wide range of diseases. This requires recording many other parameters, such as blood pressure, heart rate, respiratory rate, galvanic skin reflex (GSR), body position and limb movements during sleep, oxygen saturation, respiratory movements of the chest and abdominal walls, etc. In addition, in some cases, video monitoring of human behavior during sleep is of great importance. It is not surprising that it is no longer possible to do without computer technology to analyze the entire spectrum of polysomnographic data. Many special programs have been developed for processing polysomnography. The main problem in this area is that these programs, which cope satisfactorily with the analysis of polysomnograms in healthy people, are not effective enough in pathological conditions. To a large extent, this is due to the insufficient standardization of algorithms for assessing the stages and phases of sleep in all their diversity. The solution to this problem is facilitated by the latest classification of sleep-wake cycle disorders (American Academy of Sleep Medicine. International classification of sleep disorders, 2 ^nd ed.: Diagnostic and coding manual. Westchester, 111.: American Academy of Sleep Medicine, 2005). Another way to overcome the difficulties described above was the creation of a single format for polysomnographic records - EDF (European Data Format).

Human sleep is a set of special functional states of the brain, including four stages of slow sleep (SWS, dreamless sleep, orthodox sleep) and the rapid eye movement (REM) sleep phase (REM, dreaming sleep, paradoxical sleep, rapid eye movement sleep). Each of the listed stages and phases has its own specific features on the EEG, EMG, electro-oculogram and vegetative characteristics.

Physiological characteristics of sleep phases and stages

Phase/stage	EEG	EMG	Electrooculogram
Relaxed wakefulness	Alpha and beta rhythm	High amplitude	BDG
Stage I	Reduction of alpha rhythm; theta and delta rhythms	Decreased amplitude	Slow eye movements
Stage II	Sleep spindles, K-complexes	Decreased amplitude	Rare slow eye movements
Stage III	Delta rhythm (from 20 to 50% in the analysis period)	Low amplitude	Rare slow eye movements
Stage III	High amplitude delta rhythm (>50% of the analysis epoch)	Low amplitude	Rare slow eye movements
FBS	Sawtooth 6-rhythm, a- and beta-waves	Very low amplitude, physiological sleep myoclonus	BDG

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Causes of sleep disorders

Physical causes of sleep disturbance. Diseases and conditions that cause pain or discomfort (e.g. arthritis, cancer, herniated discs), and especially pain that worsens with movement, lead to nighttime awakenings and poor sleep quality. Treatment is aimed at the underlying disease and pain relief (e.g. prescribing analgesics before bedtime).

Mental causes of sleep disorders. 90% of people suffering from depression have pathological daytime sleepiness and insomnia, while 60-69% of people suffering from chronic insomnia usually have mental disorders manifested by mood disorders.

In depression, sleep disorders include problems falling asleep and maintaining sleep. Sometimes, in bipolar disorder and seasonal affective disorder, sleep is not disrupted, but patients complain of increased daytime sleepiness.

If depression is accompanied by insomnia, the drugs of choice should be antidepressants with a pronounced sedative effect (for example, amitriptyline, doxepin, mitrazapine, nefazodone, trazodone). These drugs are taken regularly in doses sufficient to relieve depression.

If depression is accompanied by abnormal daytime sleepiness, antidepressants with an activating effect, such as bupropion, venlafaxine, or selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline), should be prescribed.

Insufficient sleep syndrome (sleep deprivation). Chronic sleep deprivation (for various social reasons or due to work) leads to patients sleeping too little at night to feel refreshed upon awakening. This syndrome is probably the most common cause of pathological daytime sleepiness, which disappears with increased sleep duration (e.g. on weekends or holidays).

Drug-induced sleep disorders. Insomnia and abnormal daytime sleepiness may develop in response to long-term use of CNS stimulants (eg, amphetamines, caffeine), hypnotics (eg, benzodiazepines) and sedatives, anticonvulsants (eg, phenytoin), oral contraceptives, methyldopa, propranolol, thyroid hormone preparations, alcohol abuse, and after chemotherapy with antimetabolites. Insomnia may also develop during withdrawal of CNS depressants (eg, barbiturates, opioids, sedatives), tricyclic antidepressants, monoamine oxidase inhibitors, or narcotics (eg, cocaine, heroin, marijuana, phencyclidine). Commonly prescribed hypnotics disrupt the REM phase of sleep, which is manifested by irritability, apathy, and decreased mental activity. Abrupt withdrawal of sleeping pills and sedatives can cause nervous excitement, tremors, and seizures. Many psychotropic drugs induce abnormal movements during sleep.

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Functions of sleep

Traditionally, the main function of the FMS is considered to be restorative, including restoration of homeostasis of brain tissue. Thus, during delta sleep, the maximum secretion of somatotropic hormone (STH), replenishment of the amount of cellular proteins and ribonucleic acids, and macroergic compounds are detected. At the same time, in recent years it has become clear that in a state of slow sleep, the brain does not stop processing information, but changes - from processing exteroceptive impulses, the brain switches to analyzing interoceptive ones.

Thus, the function of the FMS includes the assessment of the state of internal organs. The functions of the FBS are the processing of information and the creation of a program of behavior for the future. During the FBS, the brain cells are extremely active, but information from the "inputs" (sense organs) does not reach them and is not sent to the "outputs" (muscular system). This is the paradoxical nature of this state, reflected in its name. Apparently, during this, the information that was received during the previous wakefulness and is stored in the memory is intensively processed. According to the hypothesis of M. Jouvet, during the FBS, genetic information related to the organization of holistic behavior is transferred to the working memory, realized at the neuronal level. Confirmation of this kind of intensive mental processes is the appearance of dreams in a person in paradoxical sleep.

Neurochemistry of Sleep

Along with traditional sleep-inducing neurochemical factors such as GABA and serotonin (for FMS), norepinephrine, acetylcholine, glutamic and aspartic acids (for RBS), in recent years melatonin, delta sleep-inducing peptide, adenosine, prostaglandins (prostaglandin D ₂ ), interleukins, muramylpeptide, and cytokines have been mentioned as "sleep agents". Emphasizing the importance of prostaglandin D ₂, the enzyme involved in its formation, prostaglandin D synthase, is called the key sleep enzyme. Of great importance is the new hypothalamic system discovered at the end of the 20th century, in which orexins (orexin A, B) and hypocretin serve as mediators. Neurons containing hypocretin are localized only in the dorsal and lateral hypothalamus and project to virtually all parts of the brain, in particular, to formations involved in the regulation of the sleep-wake cycle. They have a modulating effect on noradrenalinergic neurons of the locus coeruleus, activating effects, and participate in the control of the sleep-wake cycle, eating behavior, endocrine and cardiovascular functions. Orexin A increases locomotor activity and modulates neuroendocrine functions.

Chronobiology of sleep

The sleep process is described by the "two processes" theory proposed by A. Borbely in 1982. This model considers circadian changes in the probability of sleep onset as a result of the interaction of two processes: homeostatic (process S - sleep) and chronobiological (process C - circadian). The prerequisites for the emergence of this theory were the results of experiments conducted by several groups of scientists. Firstly, in numerous experiments of biochemists and pharmacologists who tried to isolate or create a "sleep substance", it was shown that the tendency to sleep almost linearly depends on the time of preceding wakefulness. Despite the fact that it was not possible to isolate a substance that, accumulating in the brain or other parts of the body, causes an increase in drowsiness, and is neutralized as sleep progresses (the so-called "hypnotoxin"), the existence of this agent (or complex of agents) is recognized as probable by many researchers. Substances such as vasoactive intestinal peptide, β-sleep-inducing peptide, muramylcysteine, substance P, etc., claim the role of this "natural sleeping pill". Secondly, the increase in the need for sleep is accompanied by an increase in the representation of δ-activity on the EEG with the onset of sleep. It has been shown that "sleep intensity", determined by the power of δ-activity in the EEG spectrum, is maximum at the beginning of sleep, and then decreases with each subsequent cycle. Such changes, according to the authors of the theory, indicate a gradual decrease in the "tendency to sleep" as the sleep state is realized. Thirdly, even in conditions of sufficient sleep or, conversely, its complete absence, there is a circadian alternation of the level of wakefulness, the ability to concentrate, and subjectively assessed fatigue. The maximum levels of these indicators, which, according to the authors, reflect the level of brain activation, were noted in the morning, the minimum - in the evening. This indicated the presence of an independent process (process C) that does not depend on the accumulation of the tendency to sleep. A. Borbely suggested that the possibility of sleep onset (the so-called sleep gate) appears when the "sleep tendency" becomes high enough (process S is on the rise), and the level of brain activation demonstrates a regular (evening) decrease (process C is on the decline). If sleep occurs during this period, then a gradual decrease in the intensity of process S begins. The level of brain activation continues to change according to its chronobiological laws and, having passed the point of the minimum value, begins to increase. When the level of process S decreases sufficiently (most likely, after 6-8 hours of sleep), and the level of brain activation reaches sufficiently high values, the prerequisites for the natural end of sleep will appear, when even an insignificant external or internal sensory stimulus can wake a person up. In the case when sleep does not occur in the evening and the subject passes the sleep gate, for example, in the case of experimental sleep deprivation,the intensity of process S continues to increase, but it becomes more difficult to fall asleep because the level of brain activation during this period is quite high. If a person goes to bed the next night as usual, the phenomenon of δ-sleep rebound occurs, reflecting the increased intensity of process S. Later, P. Achermann and A. Borbely (1992) added an explanation for the alternation of the slow and fast sleep phases to the “two processes” model - a model of reciprocal interaction of these 2 phases. According to it, the onset of FMS is determined only by the activity of process S, and REM sleep is determined by the interaction of processes S and C. The performance of the “two processes” theory was studied on models of sleep disorders in patients with depression; with its help, it was possible to explain the occurrence of sleep disorders and the positive effect of sleep deprivation in this pathology.

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International Classification of Sleep Disorders

The International Classification of Sleep Disorders (2005) includes the following sections.

• I. Insomnia.
• II. Sleep-disordered breathing.
• III. Hypersomnias of central origin not associated with a circadian rhythm sleep disorder, sleep-disordered breathing, or other causes of disturbed nocturnal sleep.
• IV. Circadian rhythm sleep disorders.
• V. Parasomnias.
• VI. Sleep movement disorders.
• VII. Individual symptoms, normal variants and unresolved issues.
• VIII. Other sleep disorders.

Insomnia

Insomnia is "recurrent disturbances in the initiation, duration, consolidation, or quality of sleep that occur despite the presence of sufficient time and conditions for sleep and that are manifested by disturbances in daytime activities of various kinds." In this definition, it is necessary to highlight the main features, namely:

• persistent nature of sleep disturbances (they occur over several nights);
• the possibility of developing various types of sleep disorders;
• the availability of sufficient time to ensure sleep in a person (for example, lack of sleep in intensively working members of an industrial society cannot be considered insomnia);
• the occurrence of disturbances in daytime functioning in the form of decreased attention, mood, daytime sleepiness, vegetative symptoms, etc.

Insomnia (sleeplessness)

Sleep apnea syndrome

There are 12 main clinical signs of sleep apnea syndrome: loud snoring, abnormal motor activity during sleep, increased daytime sleepiness, hypnagogic hallucinations, enuresis, morning headaches, arterial hypertension, decreased libido, personality changes, decreased intelligence. In order to assume the presence of sleep apnea, it is enough to have the triad: loud snoring during sleep, insomnia manifestations with frequent episodes of awakening, daytime sleepiness.

Sleep apnea syndrome

Narcolepsy

In recent years, the hypothesis of decreased activity of the orexin/hypocretin system has been considered as the main pathogenetic mechanism of narcolepsy. It has been shown that narcolepsy in dogs is associated with disturbances in the genes responsible for the formation of orexin/hypocretin type II receptors. It has been shown that the cerebrospinal fluid of patients with narcolepsy has a reduced orexin content.

Clinical manifestations of narcolepsy include: daytime sleep attacks; cataplectic attacks; hypnagogic (when falling asleep) and, less commonly, hypnopompic (when waking up) hallucinations; cataplexy of falling asleep and waking up ("sleep paralysis"); sleep disturbances at night.

Narcolepsy

Restless Legs Syndrome and Periodic Limb Movement Disorder

There are numerous movement disorders during sleep, but they are most often considered within the framework of restless legs syndrome and periodic limb movement syndrome. The causes of these syndromes are varied: polyneuropathy, rheumatoid arthritis (>30%), parkinsonism, depression, pregnancy (11%), anemia, uremia (15-20%), caffeine abuse. The use of drugs (neuroleptics, antidepressants, benzodiazepines, dopamine agonists) or the withdrawal of some of them (benzodiazepines, barbiturates) can lead to the development of restless legs syndrome and periodic limb movement syndrome.

Restless legs syndrome and periodic limb movement syndrome have many similar features (a typical combination of pain syndrome and involuntary movements, motor phenomena that are most clearly manifested during sleep) and are often combined with each other.

Restless Legs Syndrome and Periodic Limb Movement Disorder

Sleep-related movement disorders

In addition to restless legs syndrome and periodic limb movement syndrome, this group includes night cramps, bruxism, rhythmic movement disorders, etc.

Rhythmic movement disorders (sleep related rhythmic movement disorder) - a group of stereotypical repetitive movements of the head, trunk and limbs. They are more often observed in men. There are several forms of rhythmic movement disorders.

Sleep-related movement disorders

Parasomnias

Parasomnias are various episodic events that occur during sleep. They are numerous, varied in their clinical manifestations and can be expressed in different stages and phases of sleep, as well as at the stages of transition from wakefulness to sleep and vice versa. Parasomnias can cause insomnia or drowsiness, psychosocial stress, harm to oneself and others. In some cases, parasomnias are a "mask" of a neurological, psychiatric or somatic disease.

The 2005 classification distinguishes the following groups of parasomnia: disorders of awakening (from FMS); parasomnias usually associated with FBS; other parasomnias.

Parasomnias

Sleep and other diseases

In 75% of cases, strokes develop during the daytime, the remaining 25% occur during the night's sleep. The frequency of subjective sleep disorders in strokes is 45-75%, and the frequency of objective disorders reaches 100%, and they can manifest themselves in the form of the appearance or intensification of insomnia, sleep apnea syndrome, sleep cycle inversion. Changes in the sleep structure in the acute period of stroke have an important prognostic value, are non-specific in nature, consisting in a decrease in the duration of deep stages and an increase in superficial stages and wakefulness. There is a parallel decrease in quality indicators. In certain clinical conditions (extremely severe condition or the acute stage of the disease), specific phenomena can be observed in the sleep structure, which practically do not occur in other pathological conditions. These phenomena in some cases indicate an unfavorable prognosis. Thus, the detection of the absence of deep stages of sleep, extremely high activation and segmental indicators, as well as gross asymmetry (one-sided sleep spindles, K-complexes, etc.) of brain activity indicates an unfavorable prognosis.

Sleep and other diseases