Methods of research of the autonomic nervous system

When studying the autonomic nervous system, it is important to determine its functional state. The principles of the study should be based on a clinical and experimental approach, the essence of which is functional and dynamic studies of tone, autonomic reactivity, and autonomic support of activity. Autonomic tone and reactivity provide an idea of the homeostatic capabilities of the body, and autonomic support of activity provides an idea of the adaptive mechanisms. In the presence of autonomic disorders, it is necessary to clarify the etiology and nature of the lesion in each specific case. Determine the level of damage to the autonomic nervous system: suprasegmental, segmental; the predominant interest of the brain structures: LRC (rhinencephalon, hypothalamus, brainstem), other cerebral structures, spinal cord; parasympathetic and sympathetic vegetative formations - sympathetic chain, ganglia, plexuses, parasympathetic ganglia, damage to sympathetic and parasympathetic fibers, namely their pre- and postganglionic segments.

Study of vegetative tone

By vegetative (initial) tone we mean more or less stable characteristics of the state of vegetative indicators during the period of "relative rest", i.e. relaxed wakefulness. Regulatory apparatuses that maintain metabolic balance, the relationship between the sympathetic and parasympathetic systems actively participate in providing tone.

Research methods:

1. special questionnaires;
2. tables recording objective vegetative indicators,
3. a combination of questionnaires and objective data from a study of the vegetative status.

Study of autonomic reactivity

Vegetative reactions that occur in response to external and internal stimuli characterize vegetative reactivity. The strength of the reaction (the range of fluctuations in vegetative indicators) and its duration (the return of vegetative indicators to the initial level) are significant.

When studying vegetative reactivity, it is necessary to take into account the "law of the initial level", according to which the higher the initial level, the more active and tense the system or organ is, the smaller the response possible under the action of disturbing stimuli. If the initial level is sharply changed, then the disturbing agent can cause a "paradoxical" or antagonistic reaction with the opposite sign, i.e. the magnitude of activation is probably related to the pre-stimulus level.

Methods for studying vegetative reactivity: pharmacological - administration of a solution of adrenaline, insulin, mesaton, pilocarpine, atropine, histamine, etc.; physical - cold and heat tests; impact on reflex zones (pressure): oculocardial reflex (Dagnini - Aschner), sinus-carotid (Tschermak, Hering), solar (Thomas, Roux), etc.

Pharmacological tests

Methodology for conducting tests with adrenaline and insulin. The study is conducted in the morning. In a horizontal position, after a 15-minute rest, the subject's blood pressure, heart rate, etc. are measured. Following this, 0.3 ml of a 0.1% solution of adrenaline or insulin at a dose of 0.15 U/kg is injected under the skin of the shoulder. Blood pressure, pulse, and respiration are recorded 3; 10; 20; 30 and 40 minutes after the adrenaline injection, and after the administration of insulin, the same indicators are recorded every 10 minutes for 1.5 hours. We took fluctuations exceeding 10 mm Hg as a change in systolic and diastolic pressure, an increase or decrease of 8-10 or more beats per 1 min as a change in heart rate, and a change in respiration by 3 or more per 1 min.

Evaluation of samples. Three degrees of autonomic reactivity were identified: normal, increased, decreased. In the group of healthy individuals, the following was found:

1. lack of response to the administration of a pharmacological substance in 1/3 of those examined;
2. partial (weak) vegetative reaction, characterized by a change in one or two objective indicators (blood pressure, pulse or respiration), sometimes in combination with mild subjective sensations or a change in three objective indicators without subjective sensations - in 1/3 of those examined;
3. pronounced (increased) vegetative reaction, in which there is a change in all three recorded objective indicators in combination with the manifestation of subjective complaints (feeling of heartbeat, chills, a feeling of internal tension or, conversely, weakness, drowsiness, dizziness, etc.) - in 1/3 of those examined.

Depending on the nature of vegetative shifts and subjective sensations, sympathoadrenal, vagus-insular, mixed, and biphasic reactions are distinguished (with the latter, the first phase can be sympathoadrenal and the second parasympathetic, or vice versa).

Physical activity

Methodology for conducting a cold test. Blood pressure and heart rate are measured in a lying position. Then the subject lowers the hand of the other hand to the wrist in water with a temperature of +4 °C and holds it for 1 min. Blood pressure and heart rate are recorded immediately after immersion of the hand in water, 0.5 and 1 min after immersion, and then - after the hand is taken out of the water - blood pressure and heart rate are recorded until they reach the initial level. If the heart rate is examined using an ECG, then the number of R waves or RR intervals in the specified time intervals is counted and everything is recalculated to the heart rate in 1 min.

Test evaluation. Normal vegetative reactivity - increase in systolic blood pressure by 20 mm Hg, diastolic - by 10-20 mm Hg after 0.5-1 min. Maximum increase in blood pressure - 30 sec after the start of cooling. Return of blood pressure to the initial level - after 2-3 min.

Pathological deviations:

1. hyperexcitability of vasomotors (hyperreactivity) - a strong increase in systolic and diastolic blood pressure, i.e. a pronounced sympathetic reaction (increased autonomic reactivity);
2. decreased excitability of vasomotors (hyporeactivity) - slight increase in blood pressure (increase in diastolic pressure less than 10 mm Hg), weak sympathetic reaction (reduced autonomic reactivity);
3. decrease in systolic and diastolic pressure - parasympathetic reaction (or perverted reaction).

Pressure on reflex zones

Oculocardiac reflex (Dagnini-Aschner). Test technique: after lying still for 15 minutes, record the ECG for 1 minute with subsequent counting of the heart rate for 1 minute (initial background). Then press on both eyeballs with the fingertips until a slight pain sensation appears. A Barre oculocompressor can be used (pressure 300-400 g). 15-25 seconds after the start of pressure, record the heart rate for 10-15 seconds using the ECG. Count the number of R waves for 10 seconds and recalculate for 1 minute.

It is possible to record the heart rate after the pressure has ceased for another 1-2 minutes. In this case, the heart rate is taken as the percentage increase in the RR interval during the last 10 seconds of pressure on the eyeballs against the average value of the RR intervals calculated over five 10-second RR segments before the pressure began.

You can also calculate the heart rate not from the ECG recording, but by palpation every 10 seconds for 30 seconds.

Interpretation: normal slowing of the heart rate - normal autonomic reactivity; strong slowing (parasympathetic, vagal reaction) - increased autonomic reactivity; weak slowing - decreased autonomic reactivity; no slowing - perverted autonomic reactivity (sympathetic reaction).

Normally, after a few seconds from the onset of pressure, the heart rate slows down in terms of 1 minute by 6-12 beats. The ECG shows a slowing of the sinus rhythm.

All test evaluations indicate both the strength and the nature of the reaction. However, the digital data obtained during examination of healthy people are not the same for different authors, probably due to a number of reasons (different initial heart rate, different methods of recording and processing). Due to the different initial heart rate (more or less than 70-72 beats per 1 min), it is possible to calculate using the Galyu formula:

X = HRsp/HRsi x 100,

Where HRsp is the heart rate in the sample; HRsi is the initial heart rate; 100 is the conventional HR number.

The slowing of the pulse according to Galu's formula is equal to: 100 - X.

We consider it appropriate to take the value M±a as the norm, where M is the average value of the heart rate in 1 min in the study group; o is the standard deviation from M. If the value is higher than M+g, we should talk about increased vegetative reactivity (sympathetic or parasympathetic), if the value is lower, we should talk about decreased vegetative reactivity. We consider it necessary to carry out calculations in this way for other tests of vegetative reactivity.

Results of the study of heart rate in samples from healthy individuals

Try	M±a
Oculocardiac reflex	-3.95 ± 3.77
Carotid sinus reflex	4.9 ± 2.69
Solar reflex	-2.75 ± 2.74

Carotid sino-articular reflex (Tschermak-Gering). Test technique: after 15 minutes of adaptation (rest) in a lying position, count the heart rate in 1 min (ECG recording - 1 min) - the initial background. Then alternately (after 1.5-2 s) press with fingers (index and thumb) on the area of the upper third of m. sternoclaidomastoideus slightly below the angle of the lower jaw until pulsation of the carotid artery is felt. It is recommended to begin pressure on the right side, since the effect of irritation on the right is stronger than on the left. The pressure should be light, not causing pain, for 15-20 s; from the 15th second, begin to record the heart rate using ECG for 10-15 s. Then stop the pressure and calculate the heart rate per minute based on the frequency of the R waves of the ECG. The calculation can be made based on the RR interval, as in the study of the oculocardiac reflex. The state of aftereffect can also be recorded at 3 and 5 minutes after the pressure is stopped. Sometimes arterial pressure and respiratory rate are recorded.

Interpretation: values obtained from healthy subjects are considered normal changes in heart rate, i.e. normal autonomic reactivity.

Values above this indicate increased vegetative reactivity, i.e. increased parasympathetic or insufficient sympathetic activity, while values below this indicate decreased vegetative reactivity. Increased heart rate indicates a distorted reaction. According to other authors [Rusetsky I. I., 1958; Birkmayer W., 1976, and others], the norm is considered to be a slowdown in heart rate after 10 s to 12 beats per 1 min, a decrease in arterial pressure to 10 mm, a slowdown in respiratory rate, and sometimes an increase in the T wave on the ECG by at least 1 mm.

Pathological deviations: sudden and significant slowing of heart rate without a drop in blood pressure (vagocardiac type); a strong drop in blood pressure (above 10 mm Hg) without a slowing of the pulse (depressor type); dizziness, fainting without a change in blood pressure or pulse or with changes in these indicators (cerebral type) - an increase in blood pressure [Birkmayer W., 1976]. Therefore, it is advisable to calculate the values of M±a.

Solar reflex - epigastric reflex (Toma, Roux). Technique of the test: at rest, in a supine position with relaxed abdominal muscles, the ECG is recorded before the test (background), the heart rate is determined by the RR intervals of the ECG. Arterial pressure can also be examined (initial background indicators). Pressure on the solar plexus is applied with a hand until the pulsation of the abdominal aorta is felt.

At 20-30 seconds from the onset of pressure, the heart rate is recorded again for 10-15 seconds using an ECG. The heart rate is calculated based on the number of R waves on the ECG for 10 seconds and recalculated per minute. The calculation can be made based on the RR interval in the same way as when studying the oculocardiac reflex (see above).

Interpretation: the value M±o is taken as the norm. The degree of expression is determined - normal, increased or expressed, decreased and perverted reactivity and the nature of the reaction - sympathetic, vagal or parasympathetic.

According to I. I. Rusetsky (1958), W. Birkmayer (1976), several types of reaction are noted:

1. the reflex is absent or inverted (the pulse is not slowed down or accelerated enough) - sympathetic type of reaction;
2. positive reflex - slowing down over 12 beats per 1 min - parasympathetic type;
3. slowdown of 4-12 beats per 1 min - normal type.

In reactivity tests, it is possible to calculate the coefficients indicated in the study of vegetative tone. The results obtained in the tests provide an idea of the strength, character, and duration of vegetative reactions, i.e., the reactivity of the sympathetic and parasympathetic divisions of the ANS.

Research of vegetative support of activity

The study of the vegetative support of various forms of activity also carries important information about the state of the vegetative nervous system, since vegetative components are a mandatory accompaniment of any activity. We call their registration the study of the vegetative support of activity.

The indicators of vegetative support allow us to judge the adequate vegetative support of behavior. Normally, it is strictly correlated with the form, intensity, and duration of the action.

Methods of studying the vegetative support of activity

In clinical physiology, the study of vegetative support is carried out using experimental modeling of activity:

1. physical - dosed physical activity: bicycle ergometry, dosed walking, raising legs while lying in a horizontal position at 30-40° a certain number of times in a certain period of time, two-stage Master's test, dosed squats, dynamometer bench press up to 10-20 kg, etc.;
2. position test - transition from horizontal to vertical position and vice versa (orthoclinostatic test);
3. mental - mental arithmetic (simple - subtracting 7 from 200 and complex - multiplying two-digit numbers by two-digit numbers), composing words, for example 7 words with 7 letters, etc.;
4. emotional - modeling of negative emotions: threat of electric shock, reproduction of negative emotional situations experienced in the past, or special induction of negative emotions associated with the disease, induction of emotional stress using the Kurt Lewin method, etc. Modeling of positive emotions in different ways, for example, talking about a good outcome of the disease, etc. To register vegetative shifts, the following parameters are used: cardiovascular system: heart rate, PC variability, blood pressure, REG indicators, plethysmography, etc.; respiratory system - respiratory rate, etc.; the galvanic skin reflex (GSR), hormonal profile and other parameters are studied.

The studied parameters are measured at rest (initial vegetative tone) and during activity. The increase in the parameter during this period is assessed as II vegetative support of activity. Interpretation: the obtained data are interpreted as normal vegetative support of activity (shifts are the same as in the control group), excessive (shifts are more intense than in the control group), insufficient (shifts are less pronounced than in the control group).

The activity is provided mainly by the ergotropic system. Therefore, the state of the ergotropic devices was judged by the degree of deviation from the initial data.

Study of vegetative support in the orthoclinostatic test. This test has been described by many authors [Rusetsky I. I., 1958; Chetverikov N. S., 1968, and others] and has several modifications based on the Shelong hemodynamic test. We will give only two of its variants. The first variant (classical) is described in the manual by W. Birkmayer (1976); the second variant, which we have been adhering to recently, is to conduct the test and process the results obtained using the method proposed by Z. Servit (1948).

We regard orthoclinostatic tests, carried out actively and not with the help of a turntable, not only as hemodynamic tests, but also as tests for vegetative support of activity, i.e. vegetative shifts that ensure the transition from one position to another, and then the maintenance of the new position.

Method of the first variant. At rest and in a horizontal position, the heart rate and blood pressure are determined. Then the patient slowly, without unnecessary movements, gets up and stands in a comfortable position near the bed. Immediately in a vertical position, the pulse and blood pressure are measured, and then this is done at minute intervals for 10 minutes. The subject can stay in a vertical position from 3 to 10 minutes. If pathological changes appear at the end of the test, measurements should be continued. The patient is asked to lie down again; immediately after lying down, the blood pressure and heart rate are measured at minute intervals until they reach the initial value.

Interpretation. Normal reactions (normal vegetative support of activity): when standing up - a short-term increase in systolic pressure to 20 mm Hg, to a lesser extent diastolic pressure and a transient increase in heart rate to 30 per 1 min. During standing, systolic pressure may sometimes fall (by 15 mm Hg below the initial level or remain unchanged), diastolic pressure remains unchanged or rises slightly, so that the pressure amplitude against the initial level may decrease. Heart rate during standing may increase to 40 per 1 min against the initial. After returning to the initial position (horizontal), arterial pressure and heart rate should return to the initial level in 3 minutes. A short-term increase in pressure may occur immediately after lying down. There are no subjective complaints.

Violation of the vegetative support of activity is manifested by the following symptoms:

1. An increase in systolic pressure of more than 20 mm Hg.
   • Diastolic pressure also increases, sometimes more significantly than systolic pressure, in other cases it falls or remains at the same level;
   • Independent increase of only diastolic pressure upon standing up;
   • Increase in heart rate upon standing by more than 30 per 1 min;
   • When standing up, you may feel a rush of blood to your head and darkening of your vision.

All the above changes indicate excessive vegetative support.

2. A transient drop in systolic pressure by more than 10-15 mm Hg immediately after standing up. At the same time, diastolic pressure may simultaneously increase or decrease, so that the pressure amplitude (pulse pressure) is significantly reduced. Complaints: swaying and a feeling of weakness when standing up. These phenomena are interpreted as insufficient vegetative support.
3. During standing, systolic pressure drops by more than 15-20 mm Hg below the initial level. Diastolic pressure remains unchanged or rises slightly - hypotonic regulation disorder, which can also be regarded as insufficient vegetative support, as an adaptation disorder. A drop in diastolic pressure (hypodynamic regulation according to W. Birkmayer, 1976) can also be regarded in the same way. A decrease in the amplitude of arterial pressure compared to the initial level by more than 2 times indicates not only regulatory disorders, but also, in our opinion, a disorder of vegetative support.
4. An increase in heart rate during standing by more than 30-40 per 1 min with relatively unchanged arterial pressure is excessive vegetative support (tachycardic regulatory disorder according to W. Birkmayer, 1976). Orthostatic tachypnea may occur.

ECG changes during orthoclinostatic test: increase in sinus pulse rate, increase in P wave in II and III standard leads, decrease in ST interval and flattening or negative T wave in II and III leads. These phenomena can occur either immediately after standing up or during prolonged standing. Orthostatic changes can be observed in healthy people. They do not indicate a cardiac defect: this is a violation of vegetative supply associated with sympathicotonia - excessive supply.

The rules for moving to a lying position and in a lying position are the same.

Method of the second variant. After 15 minutes of rest in a horizontal position, the subject's arterial pressure is measured, the heart rate is recorded by recording the ECG for 1 minute. The subject calmly rises to a vertical position, which takes about 8-10 seconds. After this, the ECG is again continuously recorded in a vertical position for 1 minute, the arterial pressure is recorded. Then, on the 3rd and 5th minutes of standing, the ECG is recorded for 20 seconds, and at the same time intervals after recording the ECG, the arterial pressure is measured. Then the subject lies down (clinostatic test), and again the same vegetative indices are recorded according to the above method in the same time intervals. The heart rate is recorded by counting the R waves in 10-second intervals of the ECG.

The data obtained during the minute interval of orthostatic and clinostatic tests are processed according to Z. Servit (1948). The following indicators are calculated:

1. Average orthostatic acceleration per 1 min (AOA). It is equal to the sum of the increase relative to the initial heart rate in the first 10-second segment of the minute, the second and sixth, divided by 3:

SOU = 1 + 2 + 6 / 3

Orthostatic lability index (OLI) is the difference between the highest and lowest heart rate in the orthostatic position for 1 minute (selected from six 10-second intervals of the first minute) - the minimum range of heart rate fluctuations in the orthostatic test.

Clinostatic deceleration (CD) is the greatest deceleration of heart rate within 1 minute in a lying position after moving from a vertical position.

Orthoclinostatic difference (OCD) is the difference between the greatest acceleration and the greatest deceleration during the ortho- and clinostatic tests (the calculation is also carried out for six 10-second intervals in 1 minute of the test).

The clinostatic index of lability (CIL) is the difference between the greatest and the least slowdown of the heart rate during a clinostatic test (selected from 10-second intervals of 1 minute of horizontal position). The entire calculation is carried out within 1 minute in the standing and lying positions, and then the heart rate at the 3rd and 5th minutes and the arterial pressure value are calculated. The values of M±a obtained in healthy subjects at different time intervals of the specified tests are taken as the norm.

A dynamic study of the state of the autonomic nervous system provides an idea of its initial autonomic tone (determined by the state of the peripheral autonomic formations), autonomic reactivity, and autonomic support for activity, which is determined by the state of the suprasegmental systems of the brain that organize adaptive behavior.

In addition to the above-described functional-dynamic method, which is widely used by clinicians with the registration of the specified parameters to characterize the state of the autonomic nervous system at rest and under load, REG is used, which provides indirect information on the magnitude of pulse blood filling, the state of the vascular wall of the main vessels, the relative velocity of blood flow, the relationship between arterial and venous circulation. The same problems are solved with the help of plethysmography: an increase in oscillation, i.e. dilation of blood vessels, is assessed as a decrease in sympathetic influences; a decrease in oscillation, a tendency to constriction - as their increase. Ultrasound Dopplerography (USDG) indicates the state of the vascular bed, which also indirectly reflects the state of the autonomic nervous system.

Study of neuromuscular excitability

The most commonly used objective tests are:

Inducing Chvostek's symptom at rest and after 5 minutes of hyperventilation. Inducing Chvostek's symptom is done by striking the neurological hammer at the point along the midline connecting the corner of the mouth and the earlobe. The degree of expression is measured:

• I degree - reduction of the labial commissure;
• II degree - addition of reduction of the wing of the nose;
• III degree - in addition to the phenomena described above, the orbicularis oculi muscle contracts;
• Grade IV - a sharp contraction of the muscles of the entire half of the face.

Hyperventilation for 5 minutes leads to a clear increase in the degree of expression [Аlаjouianine Th. et al., 1958; Klotz HD, 1958]. Among healthy people, a positive Chvostek symptom occurs in 3-29%. In neurogenic tetany, it is positive in 73% of cases.

Cuff test (Trousseau's symptom). Technique: an arterial tourniquet or pneumatic cuff is applied to the patient's shoulder for 5-10 minutes. The pressure in the cuff should be maintained at 5-10 mm Hg above the patient's systolic pressure. When the compression is removed in the post-ischemic stage, carpopedal spasms, the "obstetrician's hand" phenomenon, occur. The frequency of Trousseau's symptom in tetany ranges from 15 to 65%. It indicates a high level of peripheral neuromuscular excitability.

Trousseau-Bonsdorff test. Technique: a pneumatic cuff is placed on the patient's shoulder and the pressure is maintained in it for 10 minutes at a level 10-15 mm Hg higher than the patient's systolic pressure, which causes arm ischemia. In the second half of the ischemic period, hyperventilation is added (maximum deep inhalations and exhalations at a frequency of 18-20 per 1 min) for 5 minutes. Test results: weakly positive - the appearance of visible fasciculations in the interosseous muscles, especially in the area of the first interphalangeal space, a change in the shape of the hand (a tendency to develop an "obstetrician's hand"); positive - a pronounced picture of carpopedal spasm; negative - the absence of the phenomena described above.

Electromyographic study. During EMG study, a certain type of electrical activity of muscles involved in tetanic spasm is recorded. The activity is characterized by successive potentials (doublets, triplets, multiplets) that occur during short time intervals (4-8 ms) with a frequency of 125-250 pps. Such potentials and other phenomena in EMG occur during the study period using provocative tests.

Other tests that reveal neuromuscular excitability: Bechterew's elbow syndrome, Schlesinger's symptom, muscle roller symptom, but they are less informative and are used less often.

Methods of studying hyperventilation syndrome

1. Analysis of subjective sensations (complaints) characterized by polysystemicity and the connection of complaints with respiratory function.
2. The presence of respiratory disorders during or at the onset of the disease.
3. Positive results of the hyperventilation test.
4. Tests for neuromuscular excitability.
5. The possibility of stopping a hyperventilation paroxysm by inhaling an air mixture containing 5% CO2, or by breathing “into a bag” (paper or polyethylene) to accumulate one’s own CO2, with the help of which the attack is stopped.
6. The patient has hypocapnia in the alveolar air and alkalosis in the blood.

Hyperventilation test technique: the patient is in a horizontal or semi-recumbent position (in a chair). He begins to breathe deeply at a rate of 16-22 breaths per 1 min. The test lasts, depending on tolerance, from 3 to 5 minutes. A positive hyperventilation test has two variants of progression. The first variant: during the test, emotional, vegetative, tetanic and other changes occur, which disappear 2-3 minutes after its completion. The second variant: hyperventilation leads to the development of vegetative paroxysm, which, having begun during the test, continues after its termination. The transition of the test to a full-blown paroxysm is observed initially in breathing, the subject cannot stop hyperventilation and continues to breathe frequently and deeply. Respiratory distress is accompanied by vegetative, muscular-tonic and emotional disorders. It is generally accepted that the occurrence of subjective sensations during the test that resemble those that arise spontaneously is a positive criterion for establishing a diagnosis of hyperventilation syndrome.

At the age of over 50 years, the test should be carried out with caution. Contraindications are high blood pressure, the presence of cardiac and pulmonary pathology, severe atherosclerosis.

Additional methods of studying the functional state of the nervous system

Research of emotional and personal characteristics

Vegetative disorders, especially at the cerebral level, are psychovegetative. Therefore, in case of vegetative disorders, it is necessary to examine the mental sphere. One of the methods of its study is a detailed study of the psychoanamnesis, iotating the presence of childhood and current psychological traumas. Clinical analysis of emotional disorders is important. Psychological examination is carried out using various methods: the method of multifaceted personality study (MIP) as modified by F. B. Berezina and M. I. Miroshnikov (1976), Spielberger, Eysenck, Cattell tests, as well as the Rorschach projective test, thematic apperception test (TAT), the test of unfinished sentences, the Rosenzweig test (frustration test), etc. The most informative tests in the study of vegetative disorders are MIP, Spielberger, Cattell.

Electrophysiological studies

EEG is used not only to clarify the localization of the process and, in some cases, its nature (epileptic hypersynchronous generalized discharges), but also to study the functional state of non-specific activating and deactivating systems of the brain during sleep, in relaxed and tense wakefulness, which is modeled by various loads: hyperventilation, light, sound stimulation, emotional stress, mental load, etc.

The most common method of testing non-specific brain systems is polygraphic recording of EEG, ECG, GSR, EMG, and respiratory rate. Shifts in these indicators reflect the relationships between ascending and descending activating systems-Mi. The relationship and state of desynchronizing (reticular formation of the brainstem) and synchronizing (thalamocortical system) brain systems is judged by visual and computer analysis of the EEG (calculation of the a-index, current synchronization index, etc.). During sleep, EEG data allow obtaining information on the characteristics of the representation of various sleep stages, their latent periods, sleep cycles, and motor activity (SMA).

In recent years, the use of computer technology has significantly increased the possibilities of neurophysiological research. The use of the averaging method has made it possible to isolate event-related potentials from spontaneous EEG, mainly those caused by sensory and motor stimuli.

Thus, the study of somatosensory evoked potentials allows for an effective and differentiated assessment of the functional state of different levels of specific and non-specific afferentation systems.

The study of the mechanisms of action organization and effector systems makes it possible to record the motor potential associated with the execution of voluntary movements and reflecting both the general processes of action organization and decision-making, as well as more local mechanisms of activation of cortical motor neurons.

Registration of contingent negative deviation (CND) is used to study the mechanisms of directed attention, motivation, and probabilistic forecasting, which allows us to assess the state of non-specific brain systems.

The study of the features of the mechanisms of topographic organization of brain activity is possible with the help of constructing spectral maps of spontaneous EEG.

Compressed spectral analysis (CSA) using the fast Fourier transform algorithm allows one to determine the spectral power of EEG rhythms and their reactivity to various functional loads, which also provides information on the state of non-specific brain systems. In addition, CSA EEG reveals the nature of interhemispheric interaction (interhemispheric asymmetry) involved in adaptive reactions.

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Study of hormonal and neurohumoral functions

Vegetative disorders are often combined with neuro-endocrine-metabolic disorders. They are based on changes in neurohormonal and neurohumoral ratios (due to changes in neurotransmitter mediation), which, in turn, are indicators of the adaptive capabilities of the body and the state of the ergo- and trophotropic systems.

In some cases, it is necessary to examine both the hormonal profile and neurohumoral relationships: thyroid function (basal metabolism using the complex radioisotope absorption method of I), the state of the hypothalamus-pituitary-adrenal cortex system (determination of corticosteroids and their metabolites in the blood and urine), examination of ovarian function (rectal temperature, pupil symptom, CII, hormonal profile), carbohydrate, protein, water-salt metabolism, etc.

In order to study the state of neurohumoral relationships, the content of catecholamines (adrenaline, noradrenaline, dopamine, DOPA and their metabolites), acetylcholine and its enzymes, histamine and its enzymes (diamine oxidase), the histaminopexic effect (HPE) of serotonin by excretion of 5-OIAC in urine is determined in the blood, urine, and cerebrospinal fluid.

At the same time, these indicators can be used to assess the state of both specific and non-specific LRK systems, as well as the reaction of the central ergo- and trophotropic apparatuses and peripheral vegetative systems.

Humoral (electrolyte) studies of sodium, potassium, total calcium, inorganic phosphorus, chlorine, carbon dioxide, magnesium help to identify latent neurogenic tetany. Coefficients indicating the ratio of monovalent ions (sodium, potassium) to bivalent (calcium, magnesium) are determined. Neurogenic tetany syndrome (NTS) is mainly normocalcemic, but there is a relative tendency to hypocalcemia. In patients with NTS, the coefficient reflecting the predominance of monovalent ions over bivalent ones is significantly increased.

Study of the functions of the segmental division of the autonomic nervous system

The development of modern teaching on the pathology of the autonomic nervous system required a revision of old methodological approaches and the development of new research methods. Special requirements are imposed on the methods being developed today. Tests for autonomic research must be:

1. sufficiently informative regarding autonomic dysfunction (quantitative assessment of results);
2. specific, with well-reproducible results in repeated studies (the coefficient of variation should not exceed 20-25%); 3) physiologically and clinically reliable (safe);
3. non-invasive;
4. easy and quick to perform.

There are still few tests that meet these requirements.

Methods developed for the study of the autonomic nervous system in the cardiovascular, sudomotor and pupillary systems meet the above requirements to a greater extent than others and therefore are entering clinical practice more quickly.

The study of segmental vegetative disorders should be conducted taking into account not only the localization of the lesion, but also the symptoms indicating the loss or irritation of peripheral vegetative formations. It is necessary, if possible, to determine their nature (sympathetic or parasympathetic). It is desirable to clarify the interest of a certain part of the vegetative arc: afferent or efferent.

Some of the methods used can provide information about suprasegmental vegetative devices, recording the initial vegetative tone, vegetative reactivity and vegetative support of activity; in addition, it is possible to obtain information about the state of the segmental parts of the vegetative nervous system.

Cardiovascular system

Methods for determining the state of the sympathetic efferent pathway

1. Determination of changes in blood pressure associated with the transition to a vertical position. The difference in systolic blood pressure in the lying position and in the 3rd minute after standing up is calculated.

Interpretation: a drop in systolic blood pressure of no more than 10 mm Hg is a normal reaction, indicating the integrity of the efferent vasoconstrictor fibers; a drop of 11-29 mm Hg is a borderline reaction; a drop of 30 mm Hg or more is a pathological reaction, indicating efferent sympathetic insufficiency.

2. Determination of changes in arterial pressure during isometric load. Using a dynamometer, determine the maximum force in one hand. Then, for 3 minutes, the patient squeezes the dynamometer with a force equal to 30% of the maximum. Calculate the difference in diastolic arterial pressure in the 3rd minute of squeezing the dynamometer and before performing the load, at rest.

Interpretation: an increase in diastolic blood pressure by more than 16 mm Hg is a normal reaction; an increase by 10-15 mm Hg is a borderline reaction; an increase by less than 10 mm Hg is a pathological reaction, indicating efferent sympathetic insufficiency.

3. Evaluation of the state of efferent vasoconstrictor sympathetic fibers. For this purpose, some tests are used, based on the registration of the plethysmogram of the hand or forearm:
   • the presentation of mental stress, a painful stimulus or sudden noise normally causes a decrease in blood filling of the hand and an increase in arterial pressure due to peripheral vasoconstriction. The absence of changes in blood filling and arterial pressure indicates damage to the efferent sympathetic fibers going to the skin vessels;
   • when performing the Valsalva maneuver or rotational test in the Barany chair, a decrease in blood filling normally occurs due to increased vasoconstriction. The absence of changes in blood filling indicates damage to the sympathetic peripheral vasoconstrictors;
   • a sharp deep breath causes a reflex constriction of the vessels of the forearms. In this test, the reaction is based on a spinal reflex, the afferent pathways of which are unknown, and the efferent pathways consist of sympathetic vasoconstrictor fibers. The absence of a decrease in blood filling in this test also indicates sympathetic efferent insufficiency;
   • During squats, passive leg raises in a prone position, the plethysmograph shows an increase in blood filling due to a decrease in vasoconstriction. When the sympathetic vasoconstrictor fibers that go to the vessels of the skeletal muscles are damaged, there are no changes in blood filling.

It should be noted that the above tests using plethysmography do not have clear quantitative boundaries of the norm and pathology, and therefore their use in general practice is limited. However, the results obtained in the group of subjects can be compared with the data of the control group.

4. Pharmacological tests:
   • Determination of plasma norepinephrine (NA) levels: Plasma norepinephrine levels are maintained by release from sympathetic nerve endings and the adrenal medulla. Since the amount of neurotransmitter released into the blood is proportional to sympathetic nervous system activity, plasma norepinephrine levels can be used as an index of sympathetic nervous activity. It is believed that decreased plasma norepinephrine levels are due to abnormal release from sympathetic efferent terminals in blood vessels rather than to changes in its uptake or diffusion across the blood-brain barrier or other membranes. In a healthy individual, plasma norepinephrine levels remain constant in the supine position and increase sharply when the individual assumes a vertical position. In central positions of the autonomic nervous system, there is a certain plasma norepinephrine level that does not change when the individual assumes a vertical position. In peripheral lesions (postganglionic sympathetic neuron), the level of norepinephrine in the supine position is sharply reduced and does not increase during the orthostatic test. Thus, it is possible to differentiate preganglionic lesions from postganglionic ones:
   • tyramine test: tyramine releases norepinephrine and dopamine from postganglionic presynaptic vesicles. An insufficient increase in plasma norepinephrine (catecholamines) after tyramine administration would indicate a deficiency in the ability of the postganglionic neuron to release norepinephrine, i.e., a distal postganglionic sympathetic defect;
   • norepinephrine test: intravenous administration of small doses of norepinephrine causes a large number of cardiovascular effects in a healthy person, including an increase in systemic arterial pressure. In some patients with autonomic damage, an exaggerated arterial pressure response occurs due to the so-called denervation hypersensitivity that occurs with the destruction of presynaptic nerve endings. Conversely, complete denervation leads to a lower than normal arterial pressure response in this test;
   • Anaprilin test: the absence of a slowdown in heart rate with intravenous administration of Anaprilin (no more than 0.2 mg/kg) indicates damage to the sympathetic nerves going to the heart.
5. Registration of action potentials of sympathetic peripheral nerves going to the skin vessels, striated muscles and sweat glands. A modern electrophysiological method that allows, using the latest microelectrode technology, to record neuronal activity from peripheral autonomic nerves, to determine latent periods of autonomic responses for different types of stimuli, and to calculate the speed of excitation conduction along efferent sympathetic fibers.

Methods for determining the state of the parasympathetic efferent pathway

1. Changes in heart rate upon standing up. In healthy people, heart rate increases rapidly upon standing up (the maximum value is observed after the 15th heartbeat) and then decreases after the 30th beat. The ratio between the RR interval at the 15th beat and the RR interval at the 30th beat is designated as the "30:15 ratio" or "30:15" coefficient. Normally, it is equal to 1.04 or more; 1.01-1.03 is a borderline result; 1.00 is insufficient vagal influences on the heart.
2. Change in heart rate during deep, slow breathing - 6 times per 1 min. Determination of the ratio of the maximally extended RR interval during exhalation to the maximally shortened RR interval during inhalation. In healthy people, due to sinus arrhythmia caused by the influence of the vagus, this ratio is always greater than 1.21. Indicators of 1.11-1.20 are borderline. With a decrease in sinus arrhythmia, i.e. with vagus insufficiency, this indicator will not be higher than 1.10.
3. Change in heart rate during the Valsalva maneuver. The Valsalva coefficient is calculated. Breathing is done into a mouthpiece connected to a manometer; the pressure is maintained at 40 mm Hg for 15 s. At the same time, the heart rate is recorded using an ECG. Calculation of the Valsalva coefficient: the ratio of the prolonged RR interval in the first 20 s after the test to the shortened RR interval during the test. Normally, it is equal to 1.21 or more; borderline results are 1.11-1.20; a coefficient of 1.10 or lower indicates a violation of the parasympathetic regulation of the heart rhythm. Physiologically, during the test, at the moment of tension, tachycardia and vasoconstriction appear, after which a jump in blood pressure occurs and bradycardia later occurs.
4. Pharmacological tests:
   • atropine test. Complete cardiac parasympathetic block occurs with the introduction of atropine at a dose of 0.025-0.04 mg/kg, respectively from 1.8 to 3 mg of atropine sulfate. The effect is achieved within 5 minutes, lasts 30 minutes. Pronounced tachycardia is observed. In patients with damage to the cardiac branches of the vagus, there is no increase in heart rate.

Methods for determining the state of the afferent sympathetic pathway

Valsalva maneuver: breathing is performed into a mouthpiece connected to a manometer; the pressure in the manometer is maintained at 40 mm Hg for 15 s.

In this case, there is an increase in intrathoracic pressure, arterial pressure and heart rate change. All changes normally last 1.5-2 minutes and have four phases: Phase 1 - an increase in arterial pressure due to an increase in intrathoracic pressure; Phase 2 - a drop in systolic and diastolic pressure due to a change in venous inflow; after 5 seconds, the arterial pressure level is restored, which is associated with reflex vasoconstriction; Heart rate increases in the first 10 seconds; Phase 3 - a sharp drop in arterial pressure to the level of the end of the 2nd phase, which is associated with the release of the aorta; this condition lasts 1-2 seconds after the disappearance of intrathoracic pressure; Phase 4 - an increase in systolic pressure above the resting level for 10 seconds, pulse pressure increases, diastolic pressure either increases or does not change. Phase 4 ends when arterial pressure returns to its original level.

When the sympathetic afferent pathway is damaged, a blockade of the response in the 2nd phase occurs, which is expressed in a drop in systolic and diastolic pressure and an increase in heart rate.

If it is known that the vagus nerve is functioning normally (according to clinical data and test results) and at the same time there is no change in heart rate during arterial hypo- and hypertension, then it can be assumed that the afferent part of the sympathetic arc has been damaged, i.e. the path leading to the carotid sinus as part of the IX pair of cranial nerves.

Modern methods of studying vegetative apparatus in the cardiovascular system are noninvasive blood pressure monitoring and analysis of heart rate variability (spectral analysis of PC). These methods allow for an integrative quantitative assessment of vegetative function in various functional states, and to clarify the influence and role of sympathetic and parasympathetic links of vegetative regulation in the cardiovascular system.

Gastrointestinal system

The methods used to study the vegetative functions in this system are based on the study of the motility of the entire gastrointestinal tract, which is under the control of the parasympathetic and sympathetic divisions of the autonomic nervous system.

Before moving on to the description of the methods, it is necessary to warn that positive results can be interpreted as vegetative pathology in the case of exclusion of all obvious causes of gastrointestinal disorders (infection, inflammation, trauma, tumor, adhesions, liver and gallbladder pathology, etc.).

Study of excretory function. Methods for determining the state of the parasympathetic efferent pathway

1. Gastric acidity. Insulin is administered at 0.01 U/kg, followed by determination of gastric acidity. In a healthy person, acidity increases in response to hypoglycemia due to the activity of the vagus nerve. The absence of an increase in acidity indicates damage to the vagus branches that go to the parietal cells of the stomach. By the way, this is a standard procedure for assessing surgical vagotomy. If the parietal cells themselves are damaged or absent, then there will also be no increase in gastric acidity in response to pentagastrin or histamine.
2. Gastrochromoscopy. Based on the ability of the gastric mucosa to secrete a dye - neutral red - after 12-15 minutes with intramuscular administration and after 5 minutes with intravenous administration. With secretory insufficiency, the secretion of the dye is significantly delayed, with achylia - does not occur at all (predominance of the sympathetic influence).
3. Response of pancreatic polypeptides to hypoglycemia. Release of pancreatic polypeptides from the pancreas occurs during hypoglycemia and is mediated by the vagus. For this reason, insufficient or absent increase in pancreatic polypeptides in response to insulin administration is considered parasympathetic insufficiency.

Study of the motor-evacuation function of the stomach and intestines

The described methods indicate damage to the preganglionic parasympathetic fibers or sympathetic insufficiency.

Methods: scintigraphy, X-ray cinematography, manometry. It is possible to detect slowing of esophageal movements, which occurs with damage to the preganglionic parasympathetic fibers of the vagus nerve, and disturbance of the rhythm of movements with axonal degeneration of the esophageal nerves.

Contrast methods of examining the stomach and intestines, electrogastrography, and ultrasonography make it possible to detect motor function disorders in the form of slowed peristalsis and evacuation due to damage to the parasympathetic nerves (vagus) and increased motor function due to sympathetic insufficiency.

1. Balloon-kymographic method. The essence lies in recording intragastric pressure, the fluctuations of which largely correspond to stomach contractions. The initial pressure level characterizes the tone of the stomach walls. A rubber balloon filled with air is connected through a system of tubes and a Marey capsule to a water manometer. Fluctuations in the liquid in the manometer are recorded on a kymograph. When analyzing kymograms, the rhythm, strength of gastric contractions, and frequency of peristaltic waves per unit of time are assessed. Influences coming from the sympathetic nerves reduce the rhythm and strength of contraction, as well as the speed of distribution of the peristaltic wave in the stomach, and inhibit motility. Parasympathetic influences stimulate motility.
2. The open catheter method is a modification of the balloon-kymographic method. In this case, the pressure is perceived by the meniscus of the liquid.
3. Electrogastrography has the advantages of a probe-free method for assessing the motor activity of the stomach. Biopotentials of the stomach are recorded from the surface of the patient's body using the EGG-3 and EGG-4 devices. The filter system allows for the identification of biopotentials in a narrow range that characterize the motor activity of the stomach. When assessing gastrograms, the frequency, rhythm, and amplitude per unit of time are taken into account. The method involves placing an active electrode in the projection zone of the stomach on the anterior abdominal wall, which is not always possible.
4. Registration of gastric biopotentials from a remote point [Rebrov V.G., 1975] using the EGS-4M apparatus. The active electrode is on the right wrist, the indifferent one is on the right ankle.
5. Pashelectrografiya is a simultaneous study of the motor function of the stomach and intestines. The method is based on the fact that the frequency of muscle contractions is specific to different sections of the digestive tract and coincides with the frequency of the main electrical rhythm [Shede H., Clifton J., 1961; Christensen J., 1971]. By selecting this frequency using narrow-band filters, when placing electrodes on the surface of the body, it is possible to trace the nature of changes in the total potential of the corresponding sections of the gastrointestinal tract, including the small and large intestines.
6. Radio telemetry. Intragastric pressure is determined using a capsule inserted into the stomach, which includes a pressure sensor and a radio transmitter. Radio signals are received by an antenna attached to the patient's body and transmitted through a converter to a recording device. The curves are analyzed in the same way as with electrogastrography.

There are no simple, reliable, informative tests for diagnosing autonomic insufficiency in the gastrointestinal system yet.

Urogenital system

In this area, simple informative tests for the study of autonomic nerves are also still lacking; the methods used are based on the study of the functions of the final effector organs.

Methods for determining the state of the parasympathetic and sympathetic efferent pathways

1. Mictiourometry is a quantitative method that uses special devices - uroflowmeters - to assess the evacuation function of the bladder, controlled by the parasympathetic nervous system.
2. Cystometry is a quantitative method that evaluates the motor and sensory functions of the bladder. Based on the relationship between intravesical pressure and bladder volume, the level of damage can be determined: above the spinal centers, preganglionic parasympathetic fibers, postganglionic nerves.
3. Urethral pressor profilometry is a method for assessing the condition of the urethra using a constructed graph - a pressure profile along its entire length during urine evacuation. It is used to exclude pathology of the lower urinary tract.
4. Cystourethrography is a contrast method for detecting dyssynergia of the internal and external sphincters.
5. Ultrasound sonography is a modern non-invasive method of examining the functions of the bladder, allowing to evaluate all stages of urination and filling.
6. Electromyography of the external anal sphincter is a method used to diagnose dyssynergia of the external sphincter of the bladder, which functions in a similar way to the external anal sphincter.
7. Monitoring erections during night sleep - used for differential diagnostics of organic and psychogenic impotence. In case of organic damage to parasympathetic fibers, erections I are absent in the morning and during night sleep, while in healthy people and in case of psychogenic impotence erections are preserved.
8. The study of evoked cutaneous sympathetic potentials from the surface of the genitals is carried out to assess the function of the sympathetic efferent nerves. When they are damaged, the latent periods of responses are lengthened and their amplitudes are reduced.

Skin (sweating, thermoregulation)

Methods for determining the state of the efferent sympathetic pathway

1. Study of evoked skin sympathetic potentials. The method is based on the GSR phenomenon and consists of recording skin biopotentials in response to electrical stimulation of the median nerve. Since the efferent link of the GSR is the sympathetic nervous system, the characteristics of the resulting response began to be used to analyze this part of the autonomic nervous system. Four pairs of surface electrodes (20x20x1.5 mm) are placed on the palms and feet. Registration is performed using an electroneuromyograph with an amplifier sensitivity of 100 μV, in the frequency range of 1.0-20.0 Hz with an analysis epoch of 5 s. Single irregular rectangular pulses with a duration of 0.1 s are used as an electrical stimulus. The current strength is selected as standard based on the appearance of a motor response of the thumb during stimulation in the projection area of the median nerve at the wrist level. The stimuli are given randomly with an interval of at least 20 s after the extinction of spontaneous GSR. In response to the stimulus, 4-6 galvanic skin responses are averaged, which are designated as evoked skin sympathetic potentials (ESP). The latent periods and I amplitudes of the ESP are determined. The informativeness of this method was demonstrated by a series of studies in patients with various forms of polyneuropathies in systemic, endocrine and autoimmune diseases. In this case, an increase in LA and a decrease in the AMP of the ESP were assessed as a violation of excitation conduction along the autonomic sudomotor fibers, and the absence of responses - as a result of a gross violation of the function of sweat fibers. However, when analyzing the ESP, one should always take into account that the parameters of latencies and amplitudes can change not only with disorders in the peripheral, but also in the central nervous system. When interpreting the VKSP data from the point of view of the level of damage to the VNS, it is necessary to take into account the results of clinical and other paraclinical research methods (ENMG, EP, EEG, MRI, etc.). The advantages of the method are non-invasiveness, complete safety, and quantitative assessment of the results.

Another informative method is the quantitative sudomotor axon reflex test (QSART), in which local sweating is stimulated by acetylcholine iontophoresis. The intensity of sweating is recorded by a special susceptometer, which transmits information in analog form to a computer. The study is conducted in a special heat-insulated room at rest and under thermal loads (hot tea, etc.). The need for a special room and technical equipment for conducting research limits the wide application of this method.

Much less frequently nowadays, dye tests are used to assess the sweating function. Some of them are described below. The failure of the efferent part of the sympathetic reflex arc is determined by the absence of sweating in a certain area of the body. Localization is established by observing sweating using the iodine-starch test of Minor or the chromium-cobalt test of Yuzhelevsky. Sweating is achieved by various methods:

• • Aspirin test: taking 1 g of acetylsalicylic acid with a glass of hot tea causes diffuse sweating through the cerebral apparatus; in case of cortical lesions, a monoplegic type of sweating occurs more often - its absence or decrease.
  • Warming the subject in a dry-air box, a heating chamber, or immersion of two limbs in hot water (43 °C) causes spinal sweat reflexes via the cells of the lateral horns of the spinal cord. In case of damage to segmental parts of the spinal cord, warming procedures, as well as the aspirin test, reveal the absence or decrease of sweating in the corresponding areas.
  • Pilocarpine test: subcutaneous injection of 1 ml of 1% pilocarpine solution, acting on the terminal sweat glands, normally causes sweat secretion in a certain area of the body. Absence or decrease of sweating in this test is observed in the absence or damage of sweat glands.
  • Axon reflex testing: stimulation with faradic current, intradermal injection of acetylcholine (5-10 mg) or electrophoresis of acetylcholine normally cause local piloerection and sweating after 5 minutes. Absence of piloerection, decreased or absent sweating indicate damage to the sympathetic ganglia or postganglionic neurons.

2. Study of surface skin temperature using thermovisors: infrared radiation intensity is recorded, which is the essence of the obtained thermograms. Isotherm effects are used to quantify the infrared radiation value. Temperature values are recorded in degrees. Thermogram interpretation is based on the presence of thermal asymmetry, as well as the value of the longitudinal terminal gradient, reflecting the temperature difference between the distal and proximal areas of the skin. Study of thermograms and skin temperature intensity showed that the upper half of the body is warmer than the lower, the right and left limbs are characterized by a symmetrical image, the proximal parts of the limbs are warmer than the distal ones, and the difference is insignificant and gradual. In patients with cerebral autonomic disorders, the distribution of skin temperature by thermographic indicators is represented by the following types:
   • bilateral "thermoamputation" at the level of the lower third of the forearm with hypothermia of the hands and feet, with a sharp temperature drop of 2-4 °C;
   • hyperthermia of the hands and feet, more common in patients with hypothalamic syndrome;
   • different types of asymmetries:
   • unilateral "thermoamputation" of the hand;
   • asymmetry "thermoamputation" of the hands and feet.

When segmental parts of the autonomic nervous system are affected, various types of asymmetries are mainly observed.

Pupil

It is known that the sympathetic and parasympathetic systems innervate the muscles that dilate and constrict the pupil. Neuropharmacological research makes it possible to differentiate pre- and postganglionic damage to the autonomic nerves that innervate the muscles of the iris. The analysis makes it possible to differentiate the occurrence of ptosis and miosis due to damage to the sympathetic fibers of the muscle that dilates the pupil from Horner's syndrome, which is based on more proximal damage to the sympathetic pathways leading to this muscle, as well as Adie's syndrome (tonic dilation of the pupils), which is currently associated with damage to the postganglionic parasympathetic fibers that innervate the muscle that constricts the pupil, as well as from mydriasis that occurs due to damage to the preganglionic fibers.

The neuropharmacological method of analysis is based on the phenomenon of denervation hypersensitivity of postganglionic sympathetic and parasympathetic fibers. It has been shown that if there is denervation hypersensitivity of the constricted pupil in miosis or ptosis, then the lesion is localized not in the preganglionic sympathetic fiber, but in the postganglionic fiber at the base of the skull or along the internal carotid artery. If there is denervation hypersensitivity of the dilated pupil in mydriasis, then damage to the preganglionic fibers in the brainstem, cavernous sinus, or cervical spinal cord is also unlikely. This is typical for damage to the sympathetic postganglionic fibers either in the ciliary ganglion or in the outer layers of the eye.

There are several rules when examining pupils and performing neuropharmacological tests:

1. 1 drop of the drug is instilled into each eye at intervals of 2 minutes;
2. as the test is carried out to detect the defect, it may be necessary to instill the drops three times at 10-minute intervals, i.e. 6 drops in each eye;
3. in patients with unilateral pupil size abnormalities, both pupils should be examined;
4. Denervation hypersensitivity is considered to be detected if the dilated pupil contracts and the other does not respond. If there is no response, the concentration of the drug can be increased, provided that both eyes are examined. Denervation hypersensitivity of the dilated pupil can be excluded only if the normal pupil begins to contract in the absence of a stronger contraction of the dilated pupil.

In case of bilateral pupillary pathology, comparison is impossible; only one eye should be examined, and the other will serve as a control.

Sympathetic Denervation Hypersensitivity Tests in Miosis

1. Administration of 0.1% adrenaline: the normal pupil does not dilate in response to adrenaline instillation. In denervation hypersensitivity, adrenaline causes mydriasis. Maximum hypersensitivity occurs with damage to the postganglionic sympathetic pathway. The pupil dilates by more than 2 mm. Adrenaline does not cause a significant change in pupil size with damage to the preganglionic sympathetic fibers (especially the "first neuron"), i.e., in complete Horner's syndrome, this test is negative.
2. Test with 4% cocaine solution: cocaine is rarely used alone, as it does not allow to specify the location of sympathetic nerve damage, more often it is used in combination with the adrenaline test. Methodology of the combined test: 2 drops of 4% cocaine solution are administered, if necessary, this is repeated three times. Distinct mydriasis with miosis indicates damage to the preganglionic sympathetic fiber. If there is no reaction, then after 30 minutes a 0.1% adrenaline solution is instilled: slight dilation of the pupil may indicate possible damage to the preganglionic fiber, its "second neuron"; distinct dilation of the pupil is a diagnostic sign of damage to the postganglionic sympathetic fiber.

Parasympathetic Denervation Hypersensitivity Test in Mydriasis

2.5% mecholyl drops are used. 1 drop of solution is administered into each eye with repeated instillation after 5 minutes. The tonically dilated pupil reacts to mecholyl with pronounced miosis. There is no reaction in the intact pupil. This test is informative in Adie syndrome.

Internal ophthalmoplegia: identification of its causes does not require pharmacological tests, but a neurological topical analysis is needed.

In addition to pharmacological tests, there are others.

1. Pupillary cycle time. Using a slit lamp, a narrow strip of light is passed through the edge of the pupil. In response, rhythmic contractions and constriction of the pupil are observed. The time of one such cycle (constriction - expansion) in healthy people is 946 ±120 ms. An increase in the pupillary cycle time indicates parasympathetic insufficiency.
2. Polaroid photography of the pupil with an electronic flash is a method for determining pupil size in the dark. Determining the size of the dark-adapted pupil relative to the outer diameter of the iris allows one to assess the state of sympathetic innervation. Insufficient pupil dilation indicates sympathetic insufficiency. The method is sensitive to minimal changes in sympathetic function.
3. Infrared television pupillometry is a quantitative method that allows the exact dimensions of the pupil to be determined at rest, in response to light and in the dark, which provides extensive information for assessing the autonomic innervation of the pupil.
4. Heterochromia of the iris: the sympathetic nervous system affects the formation of melanin and determines the color of the iris. Disruption of the pigmentation of one iris indicates damage to the sympathetic fibers in early childhood. Depigmentation in adults is extremely rare. The cause of heterochromia in adults can be a local disease or the result of a congenital isolated anomaly. Depigmentation can be observed with other symptoms of sympathetic innervation damage in Horner's syndrome (usually congenital).