RU2371193C2 - Method of tactic therapy selection for chronic cerebral ischemia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly therapy and neurology and selection of treatment tactics for chronic cerebral ischemia cases. It involves determination of electrophoretic mobility of erythrocytes. Its rise above 1.26±0.02 indicates preservation of adaptation reserves and suitability of administering adaptogens of herbal origin for activation of stress-realising body systems. Electrophoretic mobility fallen under 1.21±0.012 indicates depletion of body adaptation capacity and suitability of administering neuropeptides of stress-limiting effect.

EFFECT: enhanced treatment efficiency, reduced side effects due to taking individual features of adaptation process into account.

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Description

The invention relates to medicine, namely to drug therapy, and can be used in the treatment of patients with chronic cerebral ischemia.

The treatment of chronic cerebral ischemia (chronic cerebrovascular insufficiency) is a complex and extremely important task of modern neurology. The relevance of the problem is determined by the widespread prevalence of cerebrovascular pathology and the severe medical and social consequences of the progression of chronic cerebral ischemia (Troshin, V.D. Vascular diseases of the nervous system: Manual. / V.D. Troshin, A.V. Gustov, A.A. Smirnov // N. Novgorod: Publishing house of the Nizhny Novgorod State Medical Academy. - 2006. - 538 p.).

The choice of drug therapy for cerebrovascular insufficiency is complicated by the heterogeneity of this pathology, the frequent combination of atrophic and vascular lesions of the brain, the presence of concomitant pathology, different levels of adaptive reserve at different stages of chronic brain ischemia and individual characteristics of the body’s reactivity (Gusev, E. Ischemia of the brain. / / E.I. Gusev, V.I. Skvortsova. - M .: Medicine; 2002. - 400 p.); (Suslina Z. Vascular diseases of the brain: Epidemiology. Fundamentals of prevention. / Z. A. Suslina, Yu.Ya. Varakin, N.V. Vereshchagin // M .: MEDpress-inform. - 2006. - 256 p.). For the prototype of the present invention, a well-known method of choosing treatment tactics in patients with chronic cerebral ischemia is selected, including examination of the patient and the appointment of drug therapy. (A. Kadykov. Chronic vascular diseases of the brain (discirculatory encephalopathy). / A.S. Kadykov, L.S. Manvelov, N.V. Shakhparonova. - SPb. TEOTAR-Media, 2006. - 236 p.)

In the known method, when choosing drug therapy in the treatment of chronic cerebral ischemia, they are guided by the following areas:

1. Impact on correctable risk factors.

These include arterial hypertension, dyslipoproteinemia, smoking.

With arterial hypertension, a selection of antihypertensive drugs is carried out according to generally accepted indications. In the presence of lipid metabolism disorders, recommendations are given on the diet, and if diet therapy is ineffective, lipid metabolism correctors are prescribed. Quitting smoking is recommended.

2. Impact on the main links of pathogenesis.

2.2 The use of vasoactive drugs.

2.3 Use of antiplatelet agents.

2.4 Use of antioxidants.

2.5 Use of excitotoxicity inhibitors.

3. Symptomatic therapy - involves the use of drugs that affect the main clinical syndromes of chronic cerebral ischemia: vestibular-atactic, cephalgic, asthenoneurotic, dissomnic, paroxysmal, pyramidal, extrapyramidal, psychopathological.

Thus, the choice of therapy in patients with chronic cerebral ischemia is carried out according to general recommendations without taking into account the individual characteristics of the adaptive-adaptive process, without assessing the stage of adaptation, which changes as cerebrovascular insufficiency progresses. Drugs that affect the homeostasis of the body, adaptive processes in conditions of cerebral ischemia are prescribed irregularly and haphazardly. As a result, the effectiveness of therapeutic measures for cerebrovascular insufficiency is low and unpredictable; complications of drug therapy are manifested, manifested by decompensation of the pathology of internal organs, which, apparently, is a manifestation of the failure of adaptation mechanisms.

The objective of the invention is to increase the effectiveness of treatment by taking into account the individual characteristics of the adaptation process and reduce complications.

The problem is solved in that in the known method of choosing treatment tactics in patients with chronic cerebral ischemia, including clinical examination of the patient and the appointment of drug therapy, the patient further determines the level of adaptation of the body by studying the electrophoretic mobility of red blood cells and with its increase of more than 1.26 ± 0.02 (μm × cm) / (V × s) prescribe natural adaptogens of plant origin, and when lowering below 1.21 ± 0.012 (μm × cm) / (V × s) neuropeptides are prescribed.

The present invention meets the criterion of "novelty", as the patent information research conducted did not reveal the sources of patent and scientific literature that discredit the novelty of the invention.

The present invention meets the criterion of "inventive step", since the search did not find technical solutions with essential features of the proposed method.

As you know, the adaptation process, or the general adaptation syndrome, is characterized by the staging of the course, regardless of the factor that disrupts the body's homeostasis. There are 3 stages of the adaptation process: 1 - stage of anxiety, 2 - stage of resistance, 3 - stage of exhaustion (Selye G. Essays on the adaptation syndrome. M .: Medicine; 1960. - 215 p.). At the same time, at the first and second stages - the anxiety stage and the resistance stage - the body's adaptive reserve is not yet exhausted, and it is advisable to use drugs that activate stress-implementing systems, namely plant adaptogens, to maintain adaptive capabilities (Panossian A. The Pharmacology of plant adaptogens : an overview with particular reference to their mechanisms of action and indications / A. Panossian, G. Wikim // 8 World Congress ISAM, Moscow, Russia, 2006, p.176-177).

At the third stage of the adaptation process - the stage of exhaustion - the adaptive capabilities of the body are exhausted and the stimulation of stress-implementing systems can lead to a deterioration in the general condition. Therefore, at the third stage, it is advisable to use drugs that have a stress-limiting effect, in particular groups of neuropeptides (Konorova I. Prevention of the negative effects of emotional stress during subsequent cerebral ischemia in low-resistance animals with the Deltaran drug) / I.L. Konorova, I.V. .Gannushkina, E.V. Koplik, A.L. Antelava // Bulletin of experimental biology and medicine. - 2006; Volume 141, No. 5. - p .99-502).

The arsenal of methods for determining the level of adaptation in clinical medicine is extremely limited. Apply the following methods:

1. Determination of the level of cortisol in the blood.

2. The study of the leukocyte formula according to the method of L.Kh. Garkavi.

3. The study of heart rate variability.

Determining the level of cortisol in the blood is an expensive research method and is most informative in acute stress reactions.

The study of the leukocyte formula requires the mandatory performance of a detailed blood test and a certain skill of the researcher, since in addition to counting blood elements, a number of calculations are necessary to determine the stage of adaptation. In addition, the method was originally developed for children and its transfer to an adult cohort of neurological patients is not always correct.

The study of heart rate variability requires the use of special equipment (electrocardiograph, software) and the presence of specially trained personnel, which makes the widespread use of this method in clinical practice difficult and problematic.

The authors propose to determine the stage of the adaptation process by studying the electrophoretic mobility of peripheral blood red blood cells. The electrophoretic mobility of red blood cells (EPPE) is one of the vital parameters of homeostasis. Registration of the movement of blood cells in an electric field allows us to evaluate not only their electrokinetic potential, but also the level of adaptation of the organism as a whole (Krylov V. Electrophoretic mobility of red blood cells and stress. / V.N. Krylov, A.V. Gustov, A.V.Deryugina // Human physiology. - 1998; No. 6. - p. 108-111).

The uniform reaction of erythrocyte motility with various pathologies (neurological, somatic, psychiatric) indicates that EPE is a reflection of the general laws of the body's homeostasis. (Ryazantsev N. Typical violations of the molecular organization of the erythrocyte membrane in case of somatic and mental pathology. / N.V. Ryazantsev, V.V. Novitsky // Uspekhi Fiziologicheskikh Nauk, 2004; Volume 35, No. 1, pp. 53-65. )

From sources of information, the authors do not know how to choose a medication for chronic cerebral ischemia, taking into account the stage of the adaptation process, therefore, the set of essential features in the claimed object meets the patentability criteria of “novelty and technical level”.

The present invention allows using it to obtain the following positive effect: increasing the effectiveness of treatment of patients with chronic cerebral ischemia and reducing the frequency of complications and adverse outcomes.

To confirm the positive effectiveness of the method, studies were conducted in a neurological clinic of the Regional Clinical Hospital. N.A.Semashko and the neurological department of the clinical hospital №3.

58 patients with chronic cerebral ischemia (discirculatory encephalopathy of the first, second and third stages) who made up the main group were under observation. The average age of the patients was 48.6 ± 5.05 years, among the observed patients there were 43 women and 15 men. 15 patients had stage 1 discirculatory encephalopathy (DE), 17 had stage 2 DE, and 26 had stage 3 DE. The diagnosis was formulated in accordance with generally accepted criteria and confirmed by CT / MRI. The stage of the adaptation process was determined using EPE. The control group included 20 healthy volunteers. The main group and the control group were comparable in terms of age and sex characteristics.

The indicators of EPE in the control group and in patients with the first, second and third stage of DE are presented in the table.

Electrophoretic mobility of red blood cells in healthy and in patients with dyscirculatory encephalopathy Indicator Healthy (M ± σ) Patients with DE of the first stage (M ± σ) Patients with second stage DE (M ± σ) Patients with DE of the third stage (M ± σ) EFPE (μm × cm) / (V × s) 1.26 ± 0.02 1.55 ± 0.03 ↑ 1.82 ± 0.03 ↑ 1.21 ± 0.012 ↓ 95% trust
interval From -4.96 to +3.87 From -3.39 to +3.7 From -3.89 to +3.79 From -3.67 to +3.45 Significance level p differences from healthy P = 0.023 P = 0.002 P = 0.034 M - average value, σ - standard deviation, ↑ - increased relative to the group of healthy, ↓ - lowered relative to the group of healthy

As can be seen from the table, the EPEC indicators of patients with DE significantly differ from those in healthy individuals of the same age. In the first and second stages of DE, an increase in EPE is noted, which indicates the activation of the pituitary-adrenal gland and corresponds to the stage of activation of the general adaptation syndrome. In the third stage of DE, a decrease in EPE relative to the group of healthy is detected, which indicates the failure of the stress-responsive system and corresponds to the stage of depletion of the adaptation syndrome.

Thus, the use of drugs that activate stress-implementing systems is indicated for patients with the first and second stage of DE, when there is the possibility of an adequate response to the use of adaptogens, that is, there is a sufficient adaptive reserve. As a result of the use of adaptogens, the level of adaptive capabilities of the body increases, which increases the effectiveness of treatment and reduces the frequency of complications. At the stage of depletion of the adaptation reserve, which occurs in patients with the third stage of DE, the use of adaptogens is impractical, however, it is reasonable to include stress-limiting drugs - neuropeptides in the therapeutic complex, which allows adaptation systems to switch to a more economical mode of functioning and ultimately leads to an increase adaptive capabilities of the body. Thus, the use of stress-limiting therapy in patients at the stage of depletion of the adaptation process can increase their ability to recover and reduce the frequency of complications from the internal organs and central nervous system. The application of the proposed method for the selection of therapeutic tactics increases the effectiveness of the treatment of patients with chronic ischemia of the head and reduces the frequency of complications. The method is characterized by simplicity, ease of implementation, minimal time and material costs, high information content about the stage of the adaptation process.

The proposed method is as follows. During the initial treatment of a patient with chronic cerebrovascular insufficiency, a neurological examination, a generally accepted paraclinical examination (general analysis of blood and urine, EEG, CT / MRI, ultrasound of the vessels of the head and neck, REG) are performed. In addition, the stage of the adaptation process is determined by studying the electrophoretic mobility of red blood cells. For this, 0.2 ml of blood is taken into a test tube with 0.1 ml of citrate. Blood can be drawn both from the cubital vein and from the finger. The measurement of EPPE is carried out by the method of microelectrophoresis (S. Kharamonenko. Electrophoresis of blood cells is normal and pathological. / C. C. Kharamonenko, A. A. Rakityanskaya. - Minsk: Belarus; 1974-164 p.). The principle of the method is that, in a specially designed microcamera, using a stopwatch and an ocular mesh, the speed of movement of a cell in an electric field is measured under a microscope. The installation for the determination of EPPE consists of a horizontal microcamera, a microscope, and a direct current source. Use electrodes of the Ag / AgCl system. To measure motility, a 0.1% erythrocyte suspension was placed in Tris-HCl buffer (pH 7.4) and cell movement was recorded at a current strength of 8 mA. In each experiment, the time of movement of 6 cells in two directions is recorded, while the sign of the charge changes on the electrodes with a polar switch. The magnitude of the electrophoretic mobility of red blood cells is determined by the formula:

U = S / TH,

Where

S is the distance over which the red blood cell moves;

T is the time of the movement of the red blood cell to a distance S;

H is the gradient of the potential.

The magnitude of the potential gradient is determined by the formula:

H = Y / gX,

Where

Y is the current strength;

g is the cross section of the microchamber;

X is the electrical conductivity of the medium.

Distinctive features of the method are simplicity, ease of implementation, minimal time and material costs, high information content. It takes no more than 2 minutes to determine EFPE; for analysis, only 0.2 ml of blood is needed, that is, sampling from both the ulnar vein and the finger is possible; the method immediately gives information about the stage of the adaptation process. So, in the normal case, the EPPE value is 1.26 ± 0.02 (μm × m) / (V × s); in the alarm stage, the EPPE increases to 1.55 ± 0.03 (μm × cm) / (V × s) , in the stage of resistance increases even more - to 1.82 ± 0.07 (μm × cm) / (V × s), in the stage of depletion - decreases to 1.21 ± 0.012 (μm × cm) / (V × s) (see table). After determining the stage of the adaptation process, they decide on the inclusion in the medical complex, in addition to conventional treatment, of drugs that affect the adaptation process, activating either stress-realizing or stress-limiting body systems. Gerimax Energy, a complex preparation containing ginseng and green tea extract, is used as a drug that activates stress-implementing systems of the body, and Deltaran containing delta sleep neuropeptide and glycine as a stress-limiting drug.

Clinical examples

Example 1

Patient M-va, 48 years old, was admitted to the neurological clinic of the Regional Clinical Hospital. N.A.Semashko with a diagnosis of Discirculatory encephalopathy of 3 stages, consequences of repeated acute cerebrovascular accidents in the pool of the right middle cerebral artery against the background of arterial hypertension.

Upon admission, the patient complained of impaired movement in the left limbs, headaches, sleep disturbances, fatigue, irritability, tearfulness, decreased memory for current events, and difficulties with self-care.

Neurological status revealed left-sided hemiparesis, hemianesthesia, elements of kinetic and kinesthetic apraxia, coordinating disorders, increased muscle tone of a mixed type in the left extremities, moderately pronounced mnestic disturbances, anxious, there are disorders of orientation in time and space.

General blood and urine tests - without pathology. On MRI of the brain, there are single small hypodensal foci located subcortical in the right hemisphere. EEG - diffuse changes in the bioelectric activity of the brain without focal and paroxysmal manifestations. USDG: no hemodynamically significant disorders were detected.

EPPE at admission = 0.18 (μm × cm) / (V × s), which corresponds to the third stage of the adaptation process - the stage of depletion. The EPEE indicator indicated the depletion of the adaptive reserve in this patient, which required the use of stress-limiting therapy.

Against the background of conventional treatment (cavinton and piracetam), the patient was prescribed a stress-limiting drug deltaran, which includes the neuropeptide delta sleep and glycine. The drug was administered intranasally for 10 days.

At the end of the course of treatment, an improvement in general condition was noted in the form of increased working capacity, improved self-care ability, normalized sleep, decreased irritability and tearfulness, improved memory according to cognitive tests and subjectively. EFPE at the end of the course of treatment was 0.22 (μm × cm) / (V × s), which indicated a tendency to increase adaptive capabilities.

The appointment of a stress-limiting drug has contributed to an increase in the effectiveness of treatment. Thus, the determination of the stage of the adaptation process by the method of EPE allowed us to choose the right treatment tactics.

Example 2

Patient Sh-na, 49 years old.

I was admitted to the neurological clinic of the Semashko Regional Clinical Hospital with a diagnosis of Discirculatory encephalopathy of the first stage with asthenoneurotic, cephalgic and vestibular-atactic syndrome.

Upon admission, she complained of headaches of a pressing nature, dizziness, instability when walking, irritability, anxiety, general weakness, decreased mental and physical performance.

Neurological status revealed reflexes of oral automatism, diffuse revitalization of muscle-tendon reflexes, instability in the Romberg position, dysmetria, and slight intentional tremor when performing a finger-nasal test.

On examination, anxious, emotionally unstable.

General blood and urine tests without pathology. According to brain MRI, a picture of slightly pronounced intracranial hypertension, arachnoid changes of cerebrospinal fluid character. EEG - diffuse changes in the bioelectric activity of the brain with increased activation of non-specific mid-stem structures. According to the ultrasound scan, the tortuosity of the right vertebral artery is determined, there are no hemodynamically significant violations. EFPE upon receipt of 1.58 (μm × cm) / (V × s), which corresponds to the stage of anxiety or resistance of the adaptation process and indicates the safety and increased activity of stress-reacting systems. In order to adapt the organism in conditions of chronic brain ischemia, Gerimax Energy was included in the generally accepted therapeutic complex. The patient took the drug by mouth, 1 tablet in the morning for 20 days.

As a result of the treatment, a significant improvement was noted: headaches disappeared, dizziness and instability during walking decreased significantly, and mental and physical performance increased. On examination, coordinating violations were not detected. EFPE at the end of the course of treatment was 1.47 (μm × cm) / (V × s), which indicated a trend towards normalization of stress-realizing structures.

The purpose of the drug is a stress-training action that has increased the effectiveness of treatment. Thus, the determination of the stage of the adaptation process by the method of EPE allowed us to choose the right treatment tactics.

Example 3

Healthy volunteer - a woman of 45 years. There are no complaints.

EFPE is 1.25 (μm × cm) / (V × s), which corresponds to the age norm.

In the correction of adaptation processes does not need.

Claims (1)

A method for choosing treatment tactics in patients with chronic cerebral ischemia, including clinical examination of the patient and the appointment of drug therapy, characterized in that the patient determines the level of adaptation of the body by examining the electrophoretic mobility of red blood cells, and with its increase over 1.26 ± 0.02 natural adaptogens of plant origin, and when lowering below 1.21 ± 0.012, neuropeptides.