Sleep Disorders

Sleep is a special genetically determined state of the body of warm-blooded animals (ie mammals and birds), characterized by a regular sequential replacement of certain polygraphic pictures in the form of cycles, phases and stages. In this definition, you should pay attention to 3 strong 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 should be objectively recorded.

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 the registration of the EEG, which allowed us to identify the natural changes in the EEG in a dream. The next stage in the formation of somnology was the description in 1953 of E. Aserinsky and N. Kleitman of the phase of fast sleep (FBS). Since then, the minimum set of studies, absolutely necessary for assessing the stages and phases of sleep, are EEG, electro-oculogram (EOG) and EMG. Another important development stage is the creation of the "Bible" of modern somnology: the leadership of A. Rechtchaffen and A. Kales (A manual of standartized terminology, techniques and scoring for sleep stages of human subjects, Bethesda, Washington DC, US Government Printing Office, 1968) , which allowed to unify and standardize the technique of polysomnogram decoding.

Currently, in the context of somnology, the following diseases and conditions are actively studied: insomnia, hypersomnia, sleep apnea syndrome and other breathing disorders in the dream, restless leg syndromes, periodic limb movements and other motor disorders in sleep, parasomnia, epilepsy, etc. . The list of these directions indicates that it is a question of 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. For this, many other parameters such as blood pressure, heart rate, respiratory movement frequency, skin-galvanic reflex (GSR), the position of the body and movements of the limbs in the dream, oxygen saturation, respiratory movements of the thoracic and abdominal walls, etc., are also required. In addition, in some cases, video monitoring of human behavior in sleep is important. Not surprisingly, to analyze the entire spectrum of polysomnographic data, it is already impossible to do without computer technology. A lot of special programs for processing polysomnography have been developed. The main problem in this direction is that these programs, which satisfactorily manage the analysis of the polysomnogram in healthy people, are not effective enough in conditions of pathology. To a large extent this is due to the insufficient standardization of the algorithms for assessing the stages and phases of sleep in all their diversity. The latest classification of disturbances in the sleep-wake cycle (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) contributes to this issue . Another way to overcome the difficulties described above was to create a single format for polysomnographic records - EDF (European Data Format).

A person's dream is a set of special functional states of the brain, including four stages of slow sleep (FMS, dreamless sleep, orthodox sleep) and a fast sleep phase (FBS, sleep with dreams, paradoxical sleep, sleep with fast eye movements). Each of the listed stages and phases has its own specific features on EEG, EMG, electro-oculogram and vegetative characteristics.

Physiological characteristics of phases and stages of sleep

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

[1], [2], [3], [4], [5], [6], [7], [8]

Causes of sleep disorders

Physical causes of sleep disorders. Diseases and conditions accompanied by a pain syndrome or a feeling of discomfort (for example, arthritis, cancer, herniated discs), and especially aggravation of pain during movement, lead to night awakenings and poor quality of sleep. Treatment is aimed at the underlying disease and alleviation of the pain syndrome (eg, prescribing analgesics before bedtime).

Mental causes of sleep disorders. 90% of those suffering from depression have pathological daytime drowsiness and insomnia, in turn, in 60-69% of people with chronic insomnia, mental disorders usually manifest as mood disorders.

In case of depression, sleep disturbances are caused by disturbed sleep and sleep disturbances. Sometimes, with bipolar disorder and seasonal affective disorder, sleep is not disturbed, but patients complain of increased daytime sleepiness.

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

If depression is accompanied by pathological daytime drowsiness, antidepressants with an activating action, such as bupropion, venlafaxine or selective serotonin reuptake inhibitors (eg, fluoxetine, sertraline) should be given.

Syndrome of inadequate sleep (sleep deprivation). Chronic lack of sleep (for various social reasons or due to work) leads to the fact that patients sleep too little at night to feel cheerful on awakening. This syndrome is probably the most common cause of abnormal daytime sleepiness, which disappears when the duration of sleep increases (for example, on weekends or holidays).

Sleep disorders caused by the use of drugs. Insomnia and pathological daytime sleepiness may develop in response to prolonged use of CNS stimulants (eg, amphetamines, caffeine), hypnotics (eg, benzodiazepines) and sedatives, anticonvulsants (eg, phenytoin), oral contraceptives, methyldopa, propranolol, thyroid hormone , alcohol abuse and after chemotherapy with antimetabolites. Insomnia can also develop with the elimination of CNS depressants (eg, barbiturates, opioids, sedatives), tricyclic antidepressants, monoamine oxidase inhibitors or drugs (eg, cocaine, heroin, marijuana, phencyclidine). Usually prescribed sleeping pills disrupt the phase of fast sleep, which is manifested by irritability, apathy, a decrease in mental activity. Abrupt withdrawal of sleeping pills and sedatives can cause nervous excitement, tremor and convulsive seizures. Many psychotropic drugs induce pathological movements during sleep.

[9], [10], [11], [12]

Functions of sleep

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

Thus, the function of the FMS includes an assessment of the internal organs. The functions of FBS are the processing of information and the creation of a program of behavior for the future. During FBS, brain cells are extremely active, but information from the "inputs" (sensory organs) does not reach them and no "outputs" (muscular system) are given. This is the paradoxical nature of this state, reflected in its name. Apparently, at the same time, the information that was received during the previous wakefulness and stored in memory is intensively recycled. According to the hypothesis of M. Jouvet, at the time of FBS there is a transfer of genetic information related to the organization of holistic behavior, into the operative memory implemented at the neuronal level. Evidence of this kind of intense mental processes is the appearance in a paradoxical dream of a person.

Neurochemistry of sleep

Along with traditional neurochemical factors inducing sleep, such as GABA and serotonin (for FMS), norepinephrine, acetylcholine, glutamic acid and aspartic acid (for PBS), melatonin, delta-sleep-inducing peptide , adenosine, prostaglandins (prostaglandin D ₂ ), interleukins, muramylpeptide, cytokines. Stressing the importance of prostaglandin D ₂, the enzyme involved in its formation, prostaglandin D-synthase, is called the key enzyme of sleep. Of great importance is the one discovered at the end of the 20th century. A new hypothalamic system in which the mediators are orexins (orexin A, B) and hypocretin (hypocretin). Neurons containing hypocretin are localized only in the dorsal and lateral hypothalamus and are projected into 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 the noradrenalinergic neurons of the bluish locus (locus coeruleus), the activating effects, 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 describes the theory of "two processes" proposed by A. Borbely in 1982. This model considers the near-daily changes in the probability of the onset of sleep as a result of the interaction of 2 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 "sleeping substance", it was shown that the propensity to sleep almost linearly depends on the time of the previous wakefulness. Despite the fact that it was not possible to isolate a substance that accumulates in the brain or other parts of the body, causes drowsiness to build up and is not neutralized as it sleeps (the so-called "hypnotoxin"), the existence of this agent (or complex of agents) researchers. The role of this "natural hypnotic" is claimed by such substances as the vasoactive intestinal peptide, -son-inducing peptide, muramylcysteine, substance P, etc. 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 is shown that the " sleep intensity", determined from the power of δ-activity in the EEG spectrum, is maximal 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 "propensity to sleep" as the state of sleep. Thirdly, even in conditions of sufficient sleep or, on the contrary, complete absence of it, there is a 24-hour alternation of the wakefulness level, the ability to concentrate attention and subjectively evaluated fatigue. The maximum levels of these indicators, which, according to the authors, reflect the level of cerebral activation, were noted in the morning, the minimum - in the evening. This indicated the existence of the action of an independent process (process C), independent of the accumulation of propensity to sleep. A. Borbely suggested that the possibility of the onset of sleep (the so-called sleep gate) appears when the "propensity to sleep" becomes sufficiently high (process S on the rise), and the level of brain activation demonstrates a regular (evening) decline (process C on the decline) . If sleep occurs during this period, the gradual decrease in the intensity of the S process begins. The level of cerebral activation continues to change according to its chronobiological laws and, after passing through the minimum point, begins to increase. When the level of the S process decreases sufficiently (most likely after 6-8 hours of sleep) and the level of cerebral activation reaches high enough values, there will be prerequisites for a natural end of sleep, when even a small external or internal sensory stimulus can awaken a person. In the case when sleep does not occur in the evening and the subject passes the gate of sleep, for example, in the case of experimental sleep deprivation, the intensity of the S process continues to increase, but it becomes more difficult to fall asleep because the level of cerebral activation during this period is quite high. If a person goes to bed the next night as usual, then the phenomenon of δ-sleep returns arises, reflecting the increased intensity of the process S. Subsequently P. Achermann and A. Borbely (1992) added to the "two processes" model the explanation of the alternation of the slow and fast sleep phase - 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 FBS by the interaction of processes S and C. The efficiency of the "two processes" theory was studied in 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 at this pathology.

[13], [14], [15], [16], [17]

International Classification of Sleep Disorders

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

• I. Insomnia.
• II. Respiratory distress in a dream.
• III. Hypersomnia of central origin, not associated with a circadian rhythm disorder of sleep, a respiratory depression in a dream or disturbed by other reasons night sleep.
• IV. Disorders of circadian rhythm of sleep.
• V. Parasomnias.
• VI. Movement disorders in sleep.
• VII. Separate symptoms, variants of the norm and unresolved issues.
• VIII. Other sleep disorders.

Insomnia

Insomnia - "repeated violations of initiation, duration, consolidation or quality of sleep, occurring despite the availability of sufficient time and conditions for sleep and manifested by violations of daily activities of various types." In this definition it is necessary to identify the main features, namely:

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

Insomnia (insomnia)

Sleep apnea syndrome

There are 12 main clinical signs of sleep apnea syndrome: severe snoring, abnormal motor activity in sleep, increased daytime sleepiness, hypnagogic hallucinations, enuresis, morning headaches, arterial hypertension, decreased libido, personality change, decreased intelligence. In order to assume the presence of sleep apnea, it is sufficient to have a triad: a strong snore in a dream, insomnia with frequent episodes of awakening, daytime drowsiness.

Sleep apnea syndrome

Narcolepsy

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

Clinical manifestations of narcolepsy include: attacks of daytime sleep; cataplexic seizures; hypnagogic (when falling asleep) and, more rarely, hypnopopic (upon awakening) hallucinations; cataplexy of falling asleep and awakening ("sleepy paralysis"); disturbance of night sleep.

Narcolepsy

Restless legs syndrome and periodic limb movement syndrome

Movement disorders in sleep are numerous, but most often they are considered within the framework of restless legs syndrome and the syndrome of periodic limb movements. The causes of these syndromes are diverse: polyneuropathies, rheumatoid arthritis (> 30%), parkinsonism, depression, pregnancy (11%), anemia, uremia (15-20%), caffeine abuse. The use of drugs (neuroleptics, antidepressants, benzodiazepines, dopaminomimetics) or the cancellation of some of them (benzodiazepines, barbiturates) can lead to the development of restless legs syndrome and the syndrome of periodic limb movements.

Restless leg syndrome and periodic limb movements syndrome have many similarities (typical combination of pain syndrome and involuntary movements, motor phenomena, most clearly manifested during sleep) and often combine with each other.

Restless legs syndrome and periodic limb movement syndrome

Movement disorders associated with sleep

In addition to the syndrome of restless legs and the syndrome of periodic limb movements, 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 extremities. More often they are observed in men. There are several forms of rhythmic motor disorders.

Movement disorders associated with sleep

Parasomnias

Parasomnias are various episodic events that arise in a dream. They are numerous, diverse 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 themselves and others. In some cases, parasomnia is a "mask" of a neurological, psychiatric or somatic disease.

In the 2005 classification, the following groups of parasomnia are distinguished: wake-up disorders (from FMS); parasomnia, usually associated with PBS; other parasomnias.

Parasomnias

Sleep and other diseases

In 75% of cases, strokes develop during the day, the remaining 25% fall on the period of night 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 appearance or strengthening of insomnia, sleep apnea syndrome, sleep cycle inversion. Changes in the structure of sleep in the acute period of stroke have an important prognostic significance, are of a nonspecific nature, consisting in decreasing the duration of deep stages and increasing the surface stages and wakefulness. There is a parallel decrease in quality indicators. In certain clinical conditions (extremely severe condition or acute stage of the disease), specific phenomena can be observed in the structure of sleep, which practically do not arise in other pathological conditions. These phenomena in a number of cases indicate an unfavorable prognosis. Thus, the detection of a lack of deep sleep stages, extremely high activation, segmental indices, as well as gross asymmetry (unilateral carotid spindles, K complexes, etc.) of brain activity indicates an unfavorable prognosis.

Sleep and other diseases