Vascular diseases of the brain, due to their high prevalence and severe consequences for public health, represent a major medical and social problem [7], as they significantly affect the quality of life. Recently, the interest of neurologists, psychiatrists and doctors of other specialties in the problem of cognitive impairment of vascular origin that has not reached the level of dementia has increased significantly - the so-called vascular mild cognitive impairment [3]. In modern neuroscience, cognitive functions are usually understood as the most complex functions of the brain, with the help of which rational knowledge of the world is carried out. Mild cognitive impairment is characterized by a decrease in concentration, impaired short-term memory, etc. This is a deficiency of one or more functions that go beyond the age norm, but do not limit daily activities, which are a manifestation of vascular diseases of the brain, detected by neuropsychological examinations at the stage of subcompensation or decompensation. In ICD X, a mild cognitive disorder (F 06.7) is considered as an independent diagnostic position, characterized by decreased memory, learning difficulties, and a reduced ability to concentrate to perform any task for a long time. The term “moderate cognitive impairment” (MCI) is also found in foreign literature [9], and domestic neurologists have proposed distinguishing the syndrome of mild cognitive impairment [2]. Impairment of cognitive functions is judged in cases where, as a result of an acquired brain disease, there is a decrease in cognitive performance compared to a higher initial level. Early diagnosis and treatment with drugs that could stop or slow down the progression of the pathological process are of great importance [1].
There is no doubt that in the pathogenesis of vascular diseases of the brain, oxygen deficiency plays a great role, leading to limitation of aerobic energy production due to disruption of the energy-synthesizing function of the mitochondrial respiratory chain. Ultimately, there is an accumulation of reactive oxygen species, depletion of endogenous antioxidants and activation of lipid peroxidation of cell membranes. It is known that activation of lipid peroxidation is observed not only in acute, but also in chronic forms of cerebrovascular pathology. The foregoing indicates the advisability of using in complex therapy of mild cognitive impairment of vascular origin drugs that can protect the brain from hypoxia and inhibit lipid peroxidation.
One of the most promising drugs from the group of antioxidants are 3-hydroxypyridine derivatives, which can penetrate the blood-brain barrier [6]. Possessing antioxidant properties, Mexiprim inhibits free radical processes, and also, by activating superoxide dismutase, increases the activity of the physiological antioxidant system as a whole. The drug affects the physicochemical properties of the membrane, while reducing the viscosity of the lipid bilayer of the membrane and increasing its fluidity. As a result, conformational changes in the protein components of the membrane occur, leading to the activation of membrane-bound enzymes and ion channels with a modulating effect on the activity of receptor complexes (GABA, benzodiazepine, acetylcholine), which undoubtedly improves synaptic transmission and the interconnection of brain structures, thereby providing a nootropic effect. It is worth emphasizing the effect of the drug on metabolism and blood supply to the brain: it improves microcirculation and rheological properties of blood, reduces platelet aggregation.
Thus, the purpose of the study was to evaluate the effectiveness of the drug "Mexiprim" (MIR-PHARM, Russia) in patients with mild cognitive disorders of vascular origin.
The study included 18 patients with vascular cognitive impairment. The criteria for inclusion in the study were the presence of vascular diseases of the brain: hypertensive encephalopathy, initial manifestations of insufficiency of blood supply to the brain, discirculatory encephalopathy of I, II degrees, vascular encephalopathy in other diseases. Exclusion criteria were the presence of dementia. The age of the patients ranged from 40 to 75 years (mean age 58.6 + 8.9 years), among them 5 men and 13 women.
All patients were undergoing outpatient therapy or treatment in a day hospital with vascular diseases of the brain and identified mild cognitive impairment, established taking into account clinical criteria, additional research methods: color duplex scanning of the carotid artery, vertebral artery, transcranial Dopplerography, echoencephalography, cognitive potential P 300.
Among the nosological forms, initial manifestations of chronic cerebrovascular accident were detected in 3 patients, stage I discirculatory encephalopathy in 9 patients, and stage II discirculatory encephalopathy in 5 patients. Of the main vascular diseases, hypertension of I-II degree was recorded in 79%; coronary heart disease in 25% of patients.
The neurological picture of the disease was varied and manifested itself during clinical examination with the following symptoms: pyramidal - in 10 patients; cerebellar - in 3 patients; cochleovestibular - in 8 patients; sensory disorders in the form of hyposthesia in 1 patient and essential tremor in 1 patient.
In order to study the cognitive sphere, a neuropsychological study was carried out, represented by the following tests: attention with a study of concentration and selectivity of attention; on visual, visuospatial and somatosensory gnosis; study of auditory gnosis and auditory-motor coordination; dynamic praxis; speech research with a test for disautomatic and reflected speech, as well as verbal associations; study of reading, memory, counting system; research of intellectual processes with the solution of logical problems and a given flow of associations; study of the emotional and personal sphere [5, 9].
The study was conducted before the start of treatment and at the end of the course of therapy, assessing the clinical condition, neuropsychological status, as well as monitoring blood pressure and basic biochemical blood tests.
As a result of the study, a certain picture of the manifestation of mild cognitive impairment emerged (Table 1).
Table 1.
Frequency of occurrence of disorders of higher cortical functions
| Higher cortical functions | Frequency of occurrence |
| Attention | 15% |
| Visual and visuospatial gnosis | 5% |
| Somatosensory gnosis | 10% |
| Auditory gnosis and auditory-motor coordination | 10% |
| Letter | 2,5% |
| Reading | 2,5% |
| Memory | 15% |
| Counting system | 10% |
| Intelligent Processes | 13% |
| Emotional-personal sphere | 17% |
All patients received Mexiprim at a daily dose of 200 mg (5% solution, 2 ml 2 times a day) intramuscularly for 2 weeks. Next, maintenance therapy was prescribed in the form of oral administration of the drug at a dosage of 125 mg 3 times a day for 1 month. If necessary, patients received basic antihypertensive and cardiac therapy, antiplatelet and anticoagulant drugs.
An overall assessment of the effectiveness of treatment with Mexiprim revealed positive results: a decrease in the severity of emotional lability, fatigue, and dizziness was significantly more often recorded. In the neurological status during treatment with Mexiprim, positive dynamics were primarily noted in the regression of cochleovestibular and cerebellar manifestations. Blood pressure remained stable, biochemical blood tests did not reveal significant changes. None of the patients included in the study had complications or side effects.
During treatment with Mexiprim for 1.5 months, patients with mild cognitive disorders of vascular origin showed positive dynamics when assessing their neuropsychological status (Table 2).
Table 2.
Dynamics of neuropsychological status during a course of treatment with Mexiprim in patients with vascular mild cognitive impairment
| Functions | Number of patients with identified disorders (in%) | |
| Before treatment | After treatment | |
| Attention | ||
| selectivity (test) | 92,8 + 2,2 | 41,7 + 2,1 |
| concentration (test) | 87,5 + 2,1 | 45,8 + 2,2 |
| Visual and visuospatial gnosis | ||
| facial recognition (familiar portraits) | 41,7 + 2,1 | 25,0 + 2,4 |
| visuospatial gnosis (hand test) | 25,0 + 2,4 | 8,3 + 4,3 |
| Somatosensory gnosis | ||
| Forster's test | 83,3 + 2,1 | 41,7 + 2,6 |
| tactile gnosis test | 33,3 + 2,3 | 16,6 + 2,8 |
| Auditory gnosis and auditory-motor coordination | ||
| localization of sound in space | 41,7 + 2,2 | 20,8 + 2,6 |
| rhythm assessment tests | 51,0 + 2,2 | 24,0 + 2,4 |
| Dynamic Praxis | ||
| “fist-rib-palm” test | 12,5 + 3,2 | 8,33 + 4,3 |
| selection test | 21,8 + 2,2 | 8,7 + 4,1 |
| Speech | ||
| reflected speech | 25,1 + 2,4 | 13,5 +3,6 |
| Memory | ||
| -test "troika" | 78,8 + 2,6 | 52,1 + 2,1 |
| -memorizing series of numbers | 79,1 + 2,8 | 55,0 + 2,2 |
| Intelligence | ||
| solving logical problems | 87,7 + 2,8 | 28,4 + 2,1 |
| Emotional sphere | ||
| playing negative words | 54,7 + 1,9 | 50,0 + 2,9 |
| decreased tendency to remember | 47,8 + 2,2 | 34,3 + 2,3 |
| reaction to failure | 50,0 + 2,9 | 33,3 + 2,1 |
Writing was impaired in 1 patient (4.2%), who was diagnosed with essential tremor.
Thus, significant positive dynamics were revealed in the neuropsychological status of patients with mild cognitive impairment of vascular origin during a course of treatment with Mexiprim. The drug is well tolerated and has no side effects. Mexiprim can be recommended as one of the main drugs of choice in the treatment of mild cognitive impairment of vascular origin.
F. Khabirov, F.I. Devlikamova
Republican Clinical Hospital for Rehabilitation of the Ministry of Health of the Republic of Tajikistan
Kazan State Medical Academy
Literature:
1. Gusev E.I., Skvortsova V.I. Modern ideas about the treatment of acute cerebral stroke. Consilium Medicum 2000; T. 2: 2: 60-65.
2. Damulin I.V. Vascular mild cognitive impairment. Psychiatry and psychopharmacology 2005; T. 5: 38 - 41.
3. Zakharov V.V., Yakhno N.N. Memory impairment. M: GEOTAR-MED, 2003. P.160.
4. Koberskaya N. N. Cognitive potential P 300. Neurological journal 2003; 6:34.
5. Luria A.R. Lectures on general psychology. St. Petersburg: Peter, 2006. P. 229. P. 314.
6. Mexidol: use of the drug in acute cerebrovascular accident. M.: Pharmsoft LLC, 2000. 13 p.
7. Suslina Z.A., Varakin Yu.Ya. Vascular diseases of the brain. M.: Medpress-inform, 2006. P. 7. P. 88.
8. Lezak MD. Neuropsychology assessment. NY University Press 1983: 768.
9. Petersen RJ MCI as a useful clinical concept. Geriatric. Times 2004; 5: 30 – 36.
Mexiprim
Antioxidant drug. It has a wide range of pharmacological activity: it increases the body’s resistance to stress, exhibits an anxiolytic effect that is not accompanied by muscle relaxation; has nootropic properties, prevents and reduces disturbances in the learning and memory process that occur with aging and exposure to various pathogenic factors; has an anticonvulsant effect; exhibits antioxidant and antihypoxic properties; increases concentration and performance; weakens the toxic effect of alcohol.
The drug improves the metabolism of brain tissue and their blood supply, improves microcirculation and rheological properties of blood, and reduces platelet aggregation. Stabilizes the membrane structures of blood cells (erythrocytes and platelets). It has a lipid-lowering effect, reduces the content of total cholesterol and LDL.
The mechanism of action of Mexiprim is due to its antioxidant and membrane protective effect. It inhibits lipid peroxidation, increases superoxide oxidase activity, increases the lipid-protein ratio, reduces membrane viscosity, and increases its fluidity. Modulates the activity of membrane-bound enzymes (calcium-independent phosphodiesterase, adenylate cyclase, acetylcholinesterase), receptor complexes (benzodiazepine, GABA, acetylcholine), which enhances their ability to bind to ligands, helps preserve the structural and functional organization of biomembranes, transport of neurotransmitters and improve synaptic transmission. Mexiprim increases dopamine levels in the brain. Causes an increase in compensatory activation of aerobic glycolysis and a decrease in the degree of inhibition of oxidative processes in the Krebs cycle under hypoxic conditions with an increase in the content of ATP and cretin phosphate, activation of the energy-synthesizing functions of mitochondria, stabilization of cell membranes.
Pharmacokinetics
Suction
After oral administration, the drug is rapidly absorbed from the gastrointestinal tract with a half-absorption period of 0.08-0.1 hours. The Cmax value in plasma ranges from 50 ng/ml to 100 ng/ml and is achieved within 0.46-0.5 hours.
Metabolism
Intensively metabolized in the liver to form its glucuronic conjugate.
Removal
T1/2 is 4.7-5 hours. The average retention time of the drug in the body is 4.9-5.2 hours.
On average, over 12 hours, 0.3% of the active substance is excreted in the urine unchanged and 50% in the form of a glucuronic conjugate. The most intensely active substance and its glucuronic conjugate are excreted within the first 4 hours after taking the drug.
The urinary excretion rates of the active substance and its conjugated metabolite have significant individual variability.
