MEXIDOL solution for intravenous and intramuscular administration 50 mg/ml ampoule 2 ml No. 10

Cervical osteochondrosis is a disease (mostly chronic) of the cervical spine, which is based on degeneration of the cartilage fiber that makes up the bulk of the intervertebral disc. One of the complications of this pathology is impaired cerebral circulation, which can lead to chronic hypoxia of the brain and disruption of its functions, including reflex activity. One of the drugs that is used to correct endogenous intoxication and normalize oxygen metabolism in cervical osteochondrosis is Mexidol. Despite the fact that the effectiveness of the drug in the treatment of osteochondrosis has not been confirmed by evidence-based medicine, the drug is often used for grade 3-4 disorders in combination with other drugs, which allows subjective conclusions to be drawn about stable effectiveness and a high probability of positive dynamics of the therapy.

"Mexidol" for osteochondrosis of the cervical spine

Description of the drug and its properties

According to its pharmacological properties, Mexidol belongs to the group of antioxidants and antihypoxants (drugs that stimulate the destruction of oxygen molecules circulating in the blood and increase the resistance of tissues and organs to hypoxia). The active substance of the drug (biologically active component) - ethylmethylhydroxypyridine succinate - removes free radicals, unstable oxygen molecules, toxins from the blood and increases the body's susceptibility to various pathogenetic factors.

Removing toxins to which the human body is exposed every day helps normalize metabolic processes and accelerate recovery

Other pharmacological properties of Mexidol also include:

• increased fluidity and decreased viscosity of membrane shells;
• inhibition of fat peroxidation, allowing normalization of lipid-protein bonds;
• increased activity of certain enzymes (primarily those associated with the cell membrane);
• increasing the concentration of dopamine (neurotransmitter) in brain cells;
• stimulating the movement of blood and lymph in the blood vessels of the microvasculature;
• decreased platelet aggregation (fusion);
• restoration of myocardial contractility (middle muscular layer of the heart) in case of reversible disorders of cardiac function.

The drug restores normal myocardial contractility

Ethylmethylhydroxypyridine succinate has high absorption and quickly binds to the protein components of plasma, penetrating into tissues and organs. After oral administration in recommended therapeutic doses, the average period of retention of the drug in the body is at least 4-5 hours.

Note! Metabolites are excreted from the body along with urine, so the drug should be prescribed with caution to persons with severe functional and organic lesions of the renal system.

Why do you need Mexidol for cervical osteochondrosis?

Osteochondrosis is, first of all, a degenerative pathology in which deformation of the intervertebral discs occurs (the vertebrae are compressed and crush the disc located between them). An intervertebral disc is a formation of fibrocartilaginous annular plates filled with a gelatinous jelly-like core and surrounded by a connective tissue membrane. With osteochondrosis, compression of two adjacent vertebrae occurs, which puts pressure on the disc and causes displacement of the pulp, which begins to bulge and protrude through the fibrous membrane. Such displacements are called hernias and protrusions.

If you want to learn in more detail how protrusion differs from herniated intervertebral discs, and also consider the causes of manifestations, diagnosis and treatment methods, you can read an article about this on our portal.

One of the characteristic symptoms of osteochondrosis is the formation of protrusions and hernias in the spine

Hernias and protrusions can cause not only compression of the spinal endings, but also compression of the blood vessels through which blood enriched with minerals and oxygen enters the brain cells. Muscle spasms and swelling of paravertebral soft tissues can also interfere with the flow of lymph and blood. Clinically, circulatory disorders in cervical osteochondrosis of the 3rd degree are manifested by chronic headaches, instability of blood pressure, visual and auditory dysfunction.

Circulatory disorders caused by osteochondrosis are manifested by painful headaches

Mexidol allows not only to establish microcirculation of fluids in blood and lymphatic vessels, but also to improve the neurotrophic parameters of tissues, as well as reduce the degree of endogenous intoxication caused by the destruction of intervertebral disc components.

The clinically significant effect of treatment with the drug is manifested by the following result:

• relief or significant reduction in the intensity of cervicogenic headaches and dizziness;
• elimination of noise and squeaking in the ears;
• restoration of impaired visual function (disappearance of spots, flickering, ripples before the eyes);
• the severity of neurological disorders (paresis and paresthesia) decreases.

After taking the drug, limbs become less numb and the severity of neurological disorders decreases

Note! The main therapeutic effect of using Mexidol as part of a complex treatment of dystrophy and degeneration of intervertebral discs in the cervical spine is to improve blood circulation and prevent cerebral hypoxia.

Research results

The diagnosis of RCC was made in both groups based on a detailed history and thorough neurological examination. It should be noted that in the OG in 19 (17.3%) patients the disease was detected for the first time, in the remaining 91 (82.7%) - again, in the GS - 14 (14.7%) and 81 (85.3%) respectively. Almost all those who applied for inpatient care underwent a course of outpatient treatment, which either did not give a positive result, or the expected effect was incomplete. Since all patients in the compared groups experienced pain to one degree or another, much attention was paid to assessing the regression of pain. The simplest and most informative test for quantitative assessment of pain perception, according to a number of researchers [4], is the visual analogue scale (VAS), which is a straight line segment 10 cm long, where the starting point (zero) corresponds to the absence of pain, and the ending point ( ten) – unbearable pain. The patient was asked to depict the intensity of the pain experienced daily during the entire examination period, which made it possible to assess the dynamics of the patient’s perception of his pain and the effectiveness of the therapy. In the GS, severe pain syndrome (7–10 points) was observed in 29.4% of patients, moderate intensity (4–6 points) – in 53.6%, moderate intensity (1–3 points) – in 16.8% of cases (28 , 51 and 16 people respectively). In the OG the same indicators were distributed as follows: 7–10 points – 26.4% (29), 4–6 points – 51.8% (57) and 1–3 points – 21.8% (24). After completing the course of treatment, when assessing the pain syndrome in the MG, a decrease in pain by 5 or more points was noted in 48 (43.6%) patients, a decrease by 1–4 points – in 62 (56.4%). In the GS, a decrease of 5 points or more was observed in 8 (8.4%) patients, by 1–4 points – in 48 (50.5%), without dynamics – in 38 (40%), increased pain was noted in 1 ( 1.05%) case. Thus, when carrying out complex therapy using Mexidol, the results in reducing the intensity of pain in the MG are much more optimistic than in the GS.

The dynamics of pain intensity reduction during treatment are shown in Fig. 1a, b, which shows that in the MG the greatest rate of pain reduction occurs from the 10th to the 20th day of treatment, and by the day of discharge (25–30th day) in more than 50% of patients the pain syndrome is completely relieved, in others it becomes moderate, requiring the use of painkillers only periodically. In the GS (Fig. 1b) a regression of the pain syndrome is also observed, but less significant than in the OG. By the time the course of treatment is completed, patients (51.6%) with moderate pain syndrome predominate in the GS, but the number of people with pain of moderate intensity, requiring constant use of painkillers, remains significant (25.3%).

In patients with RCC in the compared groups, before treatment, various neurological symptoms were revealed in the form of anisoreflexia, tension symptoms (Lasega, Nery, Dejerine, Bonnet, Wasserman, Sicard), changes in the statics and dynamics of the spine, muscular-tonic syndrome, loss of sensitivity in the corresponding dermatomes, vegetative - trophic disorders (dry skin, thinning hair on the lower extremities, hyperkeratosis of the feet); in some cases, a decrease in strength in certain muscle groups was noted.

The vast majority of patients: 92 (83.6%) in the OG and 88 (92.6%) in the GS had unilateral lesions, 18 (16.4%) and 7 (7.4%) people, respectively, had bilateral lesions. Assessing the dynamics of clinical symptoms in both groups, it should be noted that in the OG, all patients, except one, underwent a reverse development of muscular-tonic syndrome, while in the GS - only 6 (33.3%) out of 18; In 72 (69.2%) patients with OG, tension symptoms were relieved, in GS - only in 11 (11.6%). Dynamics were observed in the reflex sphere: recovery (complete or partial) was registered in the OG in 40 (42.6%) patients, in the GS – in 14 (16.3%). No dynamics were noted in the remaining patients. Positive dynamics in the restoration of sensitivity took place in the OG in 36 (36.7%) patients, in the GS – in 13 (14.6%); muscle strength in the OG in 5 (21.7%) patients, in the GS – in 1 (6.3%). No negative dynamics were noted. Thus, the most significant regression of neurological deficit was achieved in the MG, especially in relation to muscular-tonic syndrome and tension symptoms, which, together with pain, cause the greatest suffering to patients.

In addition, it should be noted that the restoration of reflexes and sensitivity is faster than in GS, which may indicate a decrease in inflammatory and hypoxic disorders in the root and peripheral nerves, a decrease in edema, as well as the beginning of remyelination processes. In the OG, a positive trend was noted in the restoration of motor activity in patients with distal paresis: in 5 (21.7%) - complete recovery, in the remaining 18 (78.3%) - positive dynamics; in GS – complete recovery in 1 (6.2%) patient, positive dynamics – in 4 (25%) patients, without dynamics – in 11 (68.8%). It should be noted that complete recovery was recorded among patients with initially mild paresis (3.5–4.5 points) and a relatively short duration of the disease (up to 6 months). When subjectively assessing the effectiveness of treatment in the OG, 108 (98.2%) patients noted “improvement”, in the GS – 37 (38.9%).

Data from the Roland-Morris questionnaire “Pain in the lower back and impairment of life activity” before treatment revealed a pronounced disturbance in all aspects of the patients’ life activity, especially active movement outside the home and the emotional and mental sphere, sleep. The total number of points in patients was 11.6 ± 0.4 in POG-1; in PGS-1 – 11.3 ± 0.6; in POG-2 – 13.2 ± 0.9 and in PGS-2 – 14.2 ± 0.8. The presence of distal paresis significantly worsened many aspects of daily life of patients (p < 0.05). After treatment, the average values ​​of the total number of points in patients were in POG-1 – 6.8 ± 0.3; in PGS-1 – 9.6 ± 0.8; in POG-2 – 8.1 ± 0.5 and in PGS-2 – 11.9 ± 0.6. In the MG subgroups, the differences between the indicators before and after treatment were significant (p < 0.001). In GS, improvement (p < 0.05) was achieved after treatment only in PGS-2. Complex treatment including Mexidol had a positive effect on restoring sleep and reducing emotional experiences; the refusal of external support was especially convincing in 13 (56.5%) POG-2 patients, which indicated a significant improvement in motor function.

To objectively assess the rate of loss of self-care ability using the Scale for Assessing the Adaptive Status of Patients with Spinal Pathology, the degree of maladaptation (DM) was calculated, which before treatment in POG-2 was 37.6 ± 2.2%, in PGS-2 – 36.8 ± 1 .8%, in POG-1 – 22.4 ± 1.2%, in PGS-1 – 24.2 ± 1.4%. Differences between subgroups within groups were significant (p < 0.001). After treatment, a more significant decrease in DM was found among patients in the OG: in POG-1 – by 80.4%, in PGS-1 – by 47.1%; in patients with paresis: in POG-2 – by 37.8%, in PGS-2 – only by 15.2%. DM decreased significantly (p < 0.001) among patients POG-1, POG-2 and PGS-1; in PGS-2 it was not possible to achieve a significant reduction (p > 0.05). The results of therapy were assessed by the effectiveness coefficient of the treatment performed. Excellent results were observed only in POG-1. In general, patients in the groups had good and satisfactory treatment results, with a clear predominance of good scores in the OG (Fig. 2). Unsatisfactory results in PGS-2 exceeded 30%.

According to X-ray examination and MRI, all patients in both groups showed signs of spinal osteochondrosis, spondylosis and spondyloarthrosis (from 1-2 vertebrae to complete damage to the lumbosacral region). Schmorl's hernias were diagnosed in 9 (4.4%) cases, in 1 patient multiple; In 100% of cases, intervertebral posterior protrusions and (or) hernias were detected: in 28 (13.7%) - median, in 147 (71.7%) - paramedian, in 30 (14.6%) - lateral, incl. including multiple in 25 (12.2%) patients. The localization of protrusions and hernias was as follows: in 128 (62.4%) patients at the levels L5–S1, in 71 (34.6%) – L4–L5, in 4 (1.95%) – L3–L4, one each (0.5%) – at the levels L2–L3 and L1–L2. In 133 (64.8%) cases, protrusion and hernia compressed the anterior wall of the dural sac, and in 20 (9.8%) cases, a violation of liquor dynamics was noted. Lumbar stenosis was detected in 47 (22.9%) cases.

When comparing the clinical picture with MRI results, in 181 (88.3%) cases, the level of localization and direction of the protrusion corresponded to the level of detected radiculopathy, which indicates the high sensitivity of this examination method. In other cases, the localization of the protrusion or hernia did not correspond to the side and level of radiculopathy. For example, in patient Z., posterior median protrusions of the L1–L2 and L2–L3 discs measuring 3.0 and 3.5 mm were detected without signs of compression of the dural sac, and clinically and according to the results of ENMG, bilateral radiculopathy L5, S1 with secondary axonal - demyelinating lesions of both tibial nerves.

The results of ENMG are presented in the table.

* Statistically significant differences between indicators in patients before and after treatment (* p < 0.05; ** p < 0.001); # statistically significant differences between the indicators of patients after treatment and the indicators of the control group (# p < 0.05; ## p < 0.001).

According to ENMG, before treatment in both groups, even in the clinical absence of motor deficits, in patients with reflex and sensory disorders signs of demyelination were revealed not only of the spinal roots, but also of the peripheral nerves (see table). At the same time, the formation of peripheral distal paresis of the muscles of the lower extremities occurred with axonal demyelinating damage to the peripheral nerves, as evidenced by a decrease in the amplitude of the M-response (in the second subgroups p < 0.05 compared with GC) and even more pronounced (p < 0.05 ) than in the first subgroups, a decrease in SPI in motor fibers (MF). The damage to the tibial nerves in patients with paresis was more pronounced, since a statistically significant (p < 0.05) increase in terminal latency was also detected compared with HC. The study of the H-reflex showed that the processes of demyelination affected both the sensory and DV roots of S1–S2, and the tibial nerve. There were no significant differences in the latency of the H-reflex between the subgroups in the OG and GS (p > 0.05), the indicators in the subgroups (POG-1 – 33.2 ± 1.6 ms, POG-2 – 35.6 ± 1, 8, PGS-1 – 32.9 ± 1.3, PGS-2 – 36.1 ± 1.7 ms) were increased and significantly different from the GC (p < 0.05). As a result of the treatment (see table), the amplitude of the M-response in POG-2 increased significantly (p < 0.05); there were no statistically significant differences with HA (p > 0.05); in GS, the results obtained were significantly different from GC (p < 0.05). Positive dynamics in the second subgroups in the form of a decrease in terminal latency upon stimulation of the tibial nerve prevailed in POG-2 (p < 0.05). In the MG subgroups, the SPI for the DV of the tibial (p < 0.001) and peroneal (p < 0.05) nerves significantly increased, but in the second subgroups the GC result could not be achieved; the differences were significant (p < 0.05). In the GS, there was no significant increase in SPI after treatment (p > 0.05); the results obtained (except for the SPI for the peroneal nerve in PGS-1) were significantly different from those in the GC (p < 0.001). In the OG, restoration of conduction in the roots (decrease in F-wave latency) was noted in both subgroups, especially in POG-1. In the GS, the positive dynamics were insignificant in both subgroups; the results after treatment were significantly different from those in the GC (p < 0.05). Restoration of nerve impulse conduction (decrease in H-reflex latency) was detected in POG-1 (29.1 ± 1.3 ms, p < 0.05). In PGS-1 (32.1 ± 1.5 ms) and POG-2 (31.2 ± 1.4 ms) the effect was incomplete; the obtained values ​​did not differ significantly from those in the GC (p > 0.05). Only in PGS-2 the positive effect was insignificant (34.3 ± 1.6 ms).

What complications of cervical osteochondrosis are treated by Mexidol?

Osteochondrosis not only negatively affects the functional state of the spine, but also negatively affects the functioning of some internal organs (especially in cases where cervical osteochondrosis is combined with degeneration of the thoracic region): the brain, heart, and respiratory tract. For this reason, Mexidol can be prescribed to patients with osteochondrosis, both to correct blood circulation in the vessels of the brain and prevent hypoxia, and to reduce the negative consequences associated with possible complications of the underlying disease.

The drug can be prescribed to normalize blood circulation in the vessels of the brain

Secondary indications for the use of products based on ethylmethylhydroxypyridine succinate against the background of cervical and cervicothoracic osteochondrosis are:

“Physiological” or “mental” depression: how to determine the cause of the disease

The first thing to remember is that panic attacks do not appear out of the blue; there is always a reason for their “awakening”. If a person does not have an innate predisposition to a depressive state, there have been no significant events in life that “knocked him out of the rut”, in 90% of cases we are talking about problems with the physical state of vital systems - cardiovascular and circulatory. The cause of uncontrollable panic and reluctance to enjoy life in the case of osteochondrosis is degeneration of vertebral cartilage in one form or another, which leads to disruption of the functioning of surrounding nerve roots and blood vessels. The resulting protrusions, hernias or other damage to the intervertebral disc lead to compression of the vessels providing blood supply to the brain. In 60% of cases, “advanced” osteochondrosis leads to oxygen starvation of the brain. Trying to normalize its condition, the “main organ” gives alarming signals, including those of a psychological nature.

To whom are drugs based on ethylmethylhydroxypyridine succinate contraindicated?

Mexidol has virtually no absolute contraindications, and all restrictions on its use are conditional. A fairly significant contraindication for such therapy is severe kidney or liver disease, since the metabolism of ethylmethylhydroxypyridine succinate occurs in hepatocytes, and its metabolites are excreted from the body by the kidneys along with urine (some of them unchanged). For patients prone to allergic reactions and with a history of allergies to drugs in this group, treatment with Mexidol is contraindicated.

Taking Mexidol is contraindicated for people with kidney disease

Important! Mexidol and its analogues are not used in official medicine in Western countries, and preparations based on ethylmethylhydroxypyridine succinate do not have a patented international name. The lack of sufficient data on the safety of Mexidol, obtained using evidence-based medicine, does not allow its use for the treatment of minor patients, pregnant and lactating women.

What is more effective: tablets or injections?

It is more expedient to carry out Mexidol therapy using injection forms (5% solution for drip and jet administration). The solution penetrates tissues and organs faster, has higher bioavailability, and the effect of its use occurs within 1-2 hours. For mild to moderate cases of the disease, ten-day courses of intramuscular injections are usually used. In case of severe lesions and acute hypoxia of the brain, drip infusion (droppers) is indicated.

Mexidol is more effective when used in injection form

Tablets for the treatment of cervical osteochondrosis are rarely used, since one of the main goals of treatment is to stop the stage of decompensation and restore temporarily lost disability.

If you want to find out in more detail what pills are for osteochondrosis of the cervical spine, and also consider the best drugs, you can read an article about this on our portal.

Clinical and neurological monitoring of long-term treatment results in subgroups of patients

To check the durability of the achieved treatment results and evaluate them in the longer term, we examined 38 patients with RCC 6 months after completion of treatment. 21 people from the OG (11 from PGS-1 and 10 from PGS-2) and 17 from the GS (8 from PGS-1 and 9 from PGS-2) came for the return visit. Maintaining or even improving the clinical effect over six months was recorded in 17 (81.0%) of 21 patients in the group: 8 (72.7%) patients from POG-1 and 9 (90.0%) from POG- 2 and only 3 (17.6%) of 17 patients had HS (all from PGS-1). There was no deterioration of the condition in the form of increased pain in the MG; in the GS, pain resumed or intensified in 14 (82.4%) patients, and 6 (35.3%) patients were re-treated during this period of time. When studying the dynamics of pain intensity in the MG subgroups, a significant (p < 0.05) decrease was noted: from 2.78 ± 0.25 to 1.34 ± 0.18 points; on the contrary, in the GS the pain intensity increased from 3.56 ± 0.79 to 4.86 ± 0.52 points. In the MG subgroups, further regression of neurological symptoms and improvement in life activity were also observed (according to the Roland-Morris scale). In the GS, a deterioration in these indicators was noted, especially in the second subgroup. In the OG subgroups, there was a steady decrease in DM (in POG-1, DM decreased from 6.4 to 3.8%, in POG-2 - from 12.8 to 8.4%), in PGS-1 the positive result was insignificant ( from 23.4 to 22.6%), in PGS-2 maladjustment increased from 31.2 to 32.4%.

Thus, further regression of neurological symptoms, associated improvement in social adaptation and basic aspects of life in patients of the main group indicated the prolonged action of Mexidol, its positive effect on the frequency of exacerbations and the duration of remission of patients with RCC, regardless of the presence of motor deficit.

Dosage regimen

The dosage of the drug is determined not only by the degree of degenerative-dystrophic changes in the intervertebral discs and associated complications, but also by the characteristics of the pathological process (stage of subcompensation or decompensation). The scheme for using Mexidol in the stage of decompensation (when positive dynamics cannot be achieved despite competent and timely drug correction) is shown in the table below.

Table. Dosage of Mexidol for acute osteochondrosis

For complex treatment of subcompensated pain syndrome, Mexidol is used in the form of injections 2 times a day, 1-2 mg ampoules. The drug in tablet form is usually prescribed in a dosage of 125-250 mg 2-3 times a day. The duration of therapy depends on the degree of hypoxia and existing complications and is determined individually.

Important! Treatment with the drug should always begin with the use of minimal effective therapeutic doses. For most patients, this dose is 50-100 mg at a time. The maximum daily dosage is rarely used in the treatment of cervical osteochondrosis and is 0.8 g.

Comparative analysis of the effectiveness of Cerebrolysin in the treatment of patients with chronic cerebral ischemia.

Comparative analysis of the effectiveness of Cerebrolysin in the treatment of patients with chronic cerebral ischemia. Pharmacoeconomic aspects

E.I. Chukanova. Department of Neurology and Neurosurgery, Faculty of Medicine, Russian State Medical University

Due to the prevalence of vascular diseases of the brain, the variety of their forms and characteristics of the course (cerebral vascular crises, transient ischemic attacks (TIA), strokes, sometimes combined disorders of cerebral and coronary circulation), the difficulty and not always effective treatment of cerebral circulatory disorders is becoming more and more Recently, attention has been paid to their prevention, that is, early diagnosis and treatment of chronic cerebrovascular insufficiency [2, 3, 5, 6, 11, 12, 14, 16].

The pathogenesis of dyscirculatory encephalopathy is caused by cerebral circulatory failure in a relatively stable form or in the form of repeated short-term episodes of dyscirculation, which can be asymptomatic or manifest clinically. The degree of structural changes in the brain during dyscirculation can range from changes in individual neurons, gliocytes and white matter fibers to infarctions of various sizes and localization [2, 8, 16], which ultimately manifests itself as focal changes in the brain substance, diffuse changes in the white matter and cerebral atrophy.

In conditions of chronic brain hypoperfusion, compensation mechanisms are depleted, the energy supply of the brain becomes insufficient, as a result of which functional disorders first develop, and then irreversible diffuse morphological changes in the brain, which prepare the brain tissue for the development of stroke. The formation of any focus of ischemic damage is accompanied by the synthesis and secretion of a wide range of regulatory peptides, directed migration of inflammatory cells, and activation of various signaling molecules. It has been shown that when changes occur in the infarction zone, an imbalance of cytokine status occurs with a deficiency of protective anti-inflammatory interleukins and trophic factors, in particular NRF [1, 2]. NRFs are physiologically active polypeptides that regulate the growth and differentiation of neurons in developing systems and their functional stability. In adulthood, NRFs protect neuronal structures from traumatic, hypoxic, ischemic and other damage [2].

One of the drugs with proven neuroprotective and neuroregenerative effects is Cerebrolysin [1, 6, 9, 10]. It is based on natural neuropeptide and growth factors isolated from the brain of pigs. The main mechanisms of action of Cerebrolysin are the regulation of brain energy metabolism, the actual neutrophic effect and modulation of the activity of endogenous growth factors, interaction with neuropeptide and neurotransmitter systems. Experimental studies have shown that Cerebrolysin reduces the brain's need for oxygen, creating its increased resistance to hypoxia factors, the antioxidant properties of the drug have been proven due to the inhibition of free radical oxidation and lipid peroxidation, as well as a positive effect on the homeostasis of microelements (magnesium, selenium, vanadium manganese) with antioxidant properties. Cerebrolysin has also been proven to have a positive effect on the state of cholinergic neurons, accompanied by a significant change in the level of acetylcholinesterase, which apparently is one of the mechanisms of the nootropic effect of the drug [9, 10].

A pharmacoeconomic study was conducted on the effectiveness of the drug Cerebrolysin in patients with chronic cerebrovascular insufficiency.

The purpose of the study was a pharmacoeconomic analysis of the effectiveness of treatment with Cerebrolysin in patients with different stages of chronic cerebrovascular insufficiency. The objectives of the study included: studying the clinical effectiveness of Cerebrolysin in patients compared to the control group, identifying features of the progression of discirculatory encephalopathy (DE) and its outcomes in patients of the main and control groups, comparative assessment of the economic effectiveness of Cerebrolysin.

Material and methods

The study group consisted of 154 patients with DE stages I, II and III, who were undergoing outpatient treatment and receiving the drug Cerebrolysin, prescribed in a dose of 5–10 ml for 10 days. In addition, patients in the study group received “basic therapy,” which was maximally unified and included aspirin (100 mg/day), dipyridamole (150 mg/day), glycine (900 mg/day) and Enap. Enap was prescribed in an individual dose, depending on the stage of hypertension and the level of initial pressure. Blood pressure correction reached a level of 120/70 mm Hg. Art. – 140/80–85 mm Hg. Art. depending on the duration of blood pressure, the severity of cerebral perfusion disorders and the initial level of blood pressure at the beginning of the study. If the effect of Enap on lowering blood pressure was insufficient, Enap was combined with Arifon at a dose of 2.5 mg/day. The control group included 118 patients with DE, clinically comparable to patients in the study group. Patients in the control group received “basic therapy”, similar to patients in the study group. All patients of the main and control groups were treated as outpatients and were observed for a year.

The neurological status of patients was recorded before inclusion in the study, and then at the end of the 1st, 6th, and 12th months. The main and control groups were comparable in gender, age, etiology, severity and predominant localization of the pathological process. The study was conducted openly. The randomization method was used to recruit patients.

The distribution by stages of DE was: DE I – 40 patients, DE II – 51, DE III – 63 patients. The etiological factors of DE were: arterial hypertension - in 57 (37.09%) patients, atherosclerosis - in 35 (22.7%), a combination of atherosclerosis and arterial hypertension - in 62 (40.3%) patients. For the purpose of a detailed assessment of the neurological status and the possibility of subsequent data processing, the following scales were used: MFI-20, MCA:FMA (Motor Club Assessment: Functional Movement Activities), Tinnetti scale (Functional Mobility Assessment in Eldery Patients), Spielberger anxiety scale (State-Trait Anxiety Inventory), Hamilton Depression Rating Scale, Mini Mental State Examination MMSE, Recovery Locus of Control questionnaire [7].

In view of the different scales and different directions of the scales used, for the convenience of presentation and perception of the material, we found it convenient to describe the dynamics of the mentioned indicators in terms of relative changes, speaking about the percentage of improvement (or deterioration) of the corresponding indicator in relation to its initial state. At the same time, the difference (95%) between the indicators of the study and control groups, differing by more than 2.5 times, was considered reliably significant; and at 90% - 2 times.

In addition to clinical examination, all studied patients underwent laboratory, instrumental and neuroimaging studies.

Research results

After the first course of treatment with Cerebrolysin in doses of 5 and 10 ml/day, a statistically significant effect of the drug on all studied scales was observed, with the exception of its effect on the score of “violent laughter and crying”. The use of Cerebrolysin at a dose of 5 ml/day for a course of 10 days showed a lesser clinical effect, however, when considering the effect of Cerebrolysin on the severity of asthenic syndrome and indicators of emotional status, it was noted that asthenic symptoms regressed by 59.6%, the prevalence of cephalgic syndrome decreased by 91 .2%. At the same time, scores on the anxiety (9.6±2.5 points) and depression (2.9±0.8) scales indicated the absence of anxiety-phobic and depressive disorders.

In table Figure 1 shows the severity of clinical manifestations of DE at the end of the first course of treatment with Cerebrolysin compared to the control group.

In addition to the effect on the severity of asthenic syndrome, anxiety, motivation and cognitive impairment in patients with stage I DE, Cerebrolysin was also effective against axial reflexes (16.9 and 23.7%), as well as vestibular ataxia (20.9 and 37. 8%). When analyzing the clinical picture in patients with DE II and DE III, a statistically significant effect of the drug on the score of the “movement” scale, amyostatic syndrome, cerebellar and frontal ataxia was noted.

By the beginning of the second course of treatment with Cerebrolysin in patients with DE I (6th month of observation), the “trace” effect remained during treatment at both a dose of 5 and 10 ml/day. In patients with DE II and DE III, the corresponding effect remained at a dose of 10 ml/day in relation to asthenic syndrome, anxiety and motivation.

After the second course of treatment with Cerebrolysin (7th month of observation), a statistically more significant effect of the drug on the scores of the selected scales was noted (Table 2), with the exception of the degree of influence of the drug on the severity of asthenic syndrome and neuropsychological characteristics in patients with stage I DE, which is most likely due to a good restoration of these functions as a result of complex treatment. The second course of treatment with Cerebrolysin statistically significantly improved the scores on the scales of movement, ataxia, pseudobulbar and amyostatic syndromes (CI 90–95%).

The “trace” effect of Cerebrolysin persisted until the 12th month of observation at all stages of the disease.

The study also assessed the risk of progression of DE and the occurrence of acute vascular episodes during treatment with Cerebrolysin compared to the control group. The number of patients with a stable condition, with a progressive course and with episodes of exacerbations - the development of TIA and strokes, compared with the control group, was taken into account. The risks of progression of DE and the occurrence of acute vascular episodes (TIA and stroke) during treatment with Cerebrolysin compared to control are presented in Table. 3. The risk of progression and development of complications during DE is calculated using the formula: A/(A+B)/C/(C+D) [4]. As can be seen from table. 3, when treated with Cerebrolysin at various dosage regimens with two courses per year for 10 days, a statistically significant effect of the drug on the progression of the disease in patients with DE stages I, II and III was noted. The odds ratio for progression when treated with Cerebrolysin at a dose of 5 ml/day was 0.1–0.2–0.3 according to the stages of the disease, respectively, and at a dose of 10 ml/day – 0–0.15–0.26 compared with the group control – 0.6–0.6–0.64. The effect of the drug on the occurrence of strokes was equally pronounced: with DE II in the control – 0.13, with treatment with Cerebrolysin at a dose of 5 ml – 0.04, at a dose of 10 ml/day – 0.04. With DE III in the control group, the OR for stroke development was 0.15, with treatment with Cerebrolysin at a dose of 5 ml/day – 0.07, with a dose of 10 ml/day – 0.03. No strokes were observed in stage I DE.

According to the results of the analysis, treatment with Cerebrolysin in the doses used was well tolerated by patients, the percentage of side effects was 2.6% (4 patients).

Pharmacoeconomic analysis

The above calculations took into account direct medical costs (excluding costs for the treatment of concomitant diseases): for inpatient treatment, which includes the cost of bed days, consultations with specialists, examinations and non-drug treatment; and direct non-medical costs. Interhospital differences in rates were not taken into account.

When selecting price parameters, the following sources were used: information bulletin “Medicine (medicines, equipment, , pharmaceutical bulletin”, “Tariffs for medical services provided to the adult population in accordance with the Moscow city compulsory health insurance program.” The above calculations took into account direct medical costs: prices for hospitalization, beds/days in the neurological department, the cost of specialist consultations, the cost of examinations and non-drug treatment; direct non-medical costs. Inter-hospital differences in tariffs were not taken into account. The cost of drug treatment was taken as a single time slice for December 2010 and converted to American dollars at the rate of 1 US dollar = 30.5 rubles. The cost of each unit of the drug (tablet, capsule, bottle, ampoule, etc.) was calculated to determine the costs of drugs in a hospital setting and for outpatient treatment. Then the cost of each drug unit was multiplied by the number of medicinal units used, then the cost of all medicines was added up and divided by the number of patients.

When determining the cost of treatment for patients with different stages of DE included in the main and control groups (without taking into account the costs of treatment of concomitant somatic pathology) per patient (completed case), the following were taken into account: the costs of basic therapy, the costs of treatment that arose when prescribing the “basic therapy" side effects, costs of treatment of TIA, cerebrovascular crises and strokes for the entire observation period; and calculation of direct non-medical costs. The main indicator in all cases was the cost of treatment per patient. The main indicator in all cases was the cost of treatment per patient. Determining the cost of basic therapy in patients of the main and control groups with different stages of DE showed that the average cost of basic therapy was $280.6 US.

The total cost of treatment of DE of different stages, including the cost of consultations, examinations, basic therapy, as well as the cost of treatment of strokes and other vascular episodes that occurred during the observation period, including the cost of direct non-medical costs, was: for DE I – $1315.92 US; with DE II – 1820.0$ US; with DE III – $2044.0 US. Taking into account the possibility of increasing treatment costs as the disease progresses, the given figures should be increased to the following values: for DE I – $2105.4 US; with DE II – 2912.0$ US; with DE III – $3352.2 US.

After calculating the cost of treatment for patients in the control group, it was determined under conditions of treatment with Cerebrolysin. The cost of drug treatment - the cost of basic therapy and Cerebrolysin was equal to $373.6 US for a dosage of 5 ml/day, and $466.6 US for a dosage of 10 ml/day. In table Table 4 shows a calculation of the cost of TIAs and strokes that developed in various subgroups in patients receiving Cerebrolysin.

By summing up all the cost terms, we can calculate the cost of direct medical costs for the treatment of one patient per year when prescribing Cerebrolysin at various dosage regimens (Table 5)

Knowing the cost of indirect medical costs per 1 patient with TIA and stroke per year (for patients in the study group and the control group), which was 35.89 and 634.5 US$, we can calculate the cost of direct medical and non-medical costs per 1 patient per year at treatment with Cerebrolysin (Table 6).

If the cost of disease progression and the development of strokes and other vascular episodes is taken into account, these figures increased.

By summing up the cost of consultations, examinations, basic therapy, the Cerebrolysin drug itself and additional funds required for the treatment of strokes and other complications that arose during observation (including non-medical costs) in patients with various stages of DE, we obtained the following cost indicators of direct medical and non-medical costs of treating one patient per year (Table 7).

Comparative indicators of pharmacoeconomic cost-effectiveness analysis are presented in Table. 8.

It should also be noted that in the study we did not take into account the indirect costs associated with establishing disability, which are many times higher than the medical (direct and indirect) costs of treatment (especially in patients of young, working age). In addition, the costs of rehabilitation treatment for patients with stroke can significantly increase the costs of preventive treatment.

Thus, the study showed that Cerebrolysin in daily doses of 5 and 10 ml for 10 days significantly improves cognitive function and reduces the severity of asthenic syndrome and depression in patients with DE. After completion of the course of treatment, Cerebrolysin has a long-lasting trace effect, lasting up to 3-4 months due to the dosage of the treatment used. The clinical effects of Cerebrolysin are confirmed by the identified significant reduction in the rate of progression of DE, as well as a statistically significant reduction in the risk of developing TIAs and strokes. Cerebrolysin has a low percentage of side effects and is well tolerated, including by patients in older age groups.

A cost-economic analysis showed that the administration of Cerebrolysin and “basic therapy” for all dosage regimens, despite the significant cost of neuroprotective therapy, turned out to be more cost-effective compared to the cost of managing patients who received only “basic therapy” aimed at correcting risk factors development of cerebrovascular pathology, which is associated with a decrease in the rate of progression of the disease and the occurrence of exacerbations during the course of the disease - the development of TIAs and strokes.

Literature

1. Gomazkov O.A. Neurotrophic and growth factors of the brain: regulatory specificity and therapeutic potential. Sat. "Advances in Physiological Sciences". 2005; 36 (2): 1–25. 2. Gusev E.I. Skvortsova V.I. Cerebral ischemia. M.: Medicine, 2001; 248. 3. Oganov R.G. Risk factors and prevention of cardiovascular diseases. G. Quality of life. Medicine. 2003; 2: 10–15. 4. Fletcher R.I. etc. Clinical epidemiology. Fundamentals of evidence-based medicine. M.: 1998; 347. 5. Fritas G.R., Boguslavsky J. Primary prevention of stroke F neurol and psych. Stroke. 2001; Issue 1: 7–21. 6. Chukanova E.I. Encephalopathy. Diss. Doctor of Medical Sciences M.: 2005. 7. Scales, tests and questionnaires in medical rehabilitation. Rukov. for doctors and scientists co-workers / Edited by A.N. Belova and O.N. Shchepetova. M.: Antidor, 2002; 439. 8. Akai F., Hiruma S. Neurotrophic factor-like effect of FPF 1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol. 1992; 7:213–221. 9. Albretch E. et al. The effects of Cereblysin on survival and sprouting of neurons from cerebral hemispheres and from the brainstem of chick embryons in vitro. Adv Biosci. 1993; 87:341–2. 10. Alvarez XA et al. Cerebrolysin protects against neurodegeneration induced by -amyloid implants in rats. The international Journal of neuropsycholpharmacology. 2000a; 3:S359. 11. Argentine C., Prencipe M. The Burden of stroke: a need for prevention. In: Prevention of Ischemic Stroke/ Eds.C. Fieschi, M. Fischer. London: Martin Dunitz 2000; 1–5. 12. Bogousslavsky J. On behalf of the European Stroke Initiative. Stroke prevention by the practitioner. Cerebrovasc Dis. 1999; 9:Suppl 4:1–68. 13. Brunner LL Kanter DS Manson JE Primary prevention of stroke. New Eng J Med. 1995; 333:1392–1400. 14. Goldstein LB, Adams R, Becker K et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 2001; 32: 280–299. 15. Leppala JM, Virtamo J, Fogelholm R, et al. Different risk factors for different stroke subtypes. Stroke. 1999; 30:2535–2540. 16. Plum F. Neuroprotection in acute ischemic stroke. JAMA. 2001; 285:1–4.

Does Mexidol help with cervical osteochondrosis?

The opinions of doctors and patients regarding the effectiveness and advisability of using Mexidol as part of the complex treatment of cervical osteochondrosis differ. Some believe that the drug should be included in the treatment regimen for osteochondrosis, since severe forms of this disease in some cases can provoke vertebral artery syndrome - a rare complication that develops against the background of impaired blood microcirculation in the vertebral arteries. Some experts believe that the drug does not have a pronounced effect on the dynamics of the therapy, therefore, for its use there must be significant and urgent indications.

Structural and pharmacological equivalents

Mexidol has several pharmaceutical equivalents (structural analogs with the same active ingredient). Among them:

• "Neurocard";
• Astrox;
  The drug "Astrox"
• "Mexico";
• "Mexidant";
• "Mexiprim."

  
  The drug "Mexiprim"

If an allergy to ethylmethylhydroxypyridine succinate is detected, the doctor can select drugs with similar therapeutic effects and pharmacological properties. Some of them are shown in the table below.

Table. Analogues of Mexidol with a similar effect

"Elkar": dosage and method of administration

How to increase the effectiveness of treatment: useful tips

For treatment to be as effective as possible and help achieve stable remission and regression of pain and neurological symptoms, medications alone are not enough. The patient must also attend prescribed physiotherapeutic procedures and classes in a special physical therapy class, which are usually organized in clinics or hospitals.

For successful treatment, the patient must regularly visit the exercise therapy room

Recommendations for successful treatment of cervical osteochondrosis may also include:

• adjustment of the sleeping place. A mattress for patients with cervical osteochondrosis should have an anatomical shape and medium or high rigidity. The pillow should also be selected individually, taking into account the anatomical characteristics of the individual patient;
• when working sedentarily, it is important to ensure the prevention of stagnation: do a light warm-up for the neck every 1-2 hours, choose the right work furniture, make sure that the height of the chair and table corresponds to your height and build;

  
  Proper organization of the workplace is very important for the health of the spine.

• In the absence of other contraindications, it is useful to go to the pool 1-2 times a week. This helps to increase blood circulation in the vessels of the neck and strengthen the musculoskeletal corset of the spine;
• nutrition should be regular, complete and balanced. Your daily diet should include a sufficient amount of fruits, vegetables, berries, meat, fish and dairy products.

  
  The patient's diet should be complete and well balanced

If you need to take medications, it is important to pay attention to special instructions. For example, Mexidol can cause increased drowsiness, so during the period of treatment you should avoid working at heights and driving vehicles.

Material and methods

205 patients with clinical manifestations of RCC (104 women and 101 men) were examined and treated. The age of the patients ranged from 18 to 74 years. The patients were divided into two groups comparable in gender and age – the main group (MG) and the comparison group (CG). The number of OG was 110 people (56 men and 54 women), GS – 95 (49 men and 46 women). The study also included 30 apparently healthy people as a control group. The presence of paresis of individual muscles or paresis of the muscles of the foot (flexor and/or extensor group) became the main criterion by which patients were divided into subgroups, since it is motor disorders that indicate pronounced clinical manifestations of RCC, leading to long-term disability or disability of patients. The 1st subgroup OG (POG-1) included 87 (79.1%) patients with sensory and reflex disorders, the 1st subgroup GS (PGS-1) included 79 (83.2%). Subgroup 2 (POG-2 and PGS-2) consisted of patients with sensory and reflex disorders in combination with peripheral distal paresis of the muscles of the lower limb, numbering 23 (20.9%) and 16 (16.8%), respectively. All patients underwent a course of standard medication and physiotherapy; in the MG, Mexidol was additionally used, 2 ml of a 5% solution 2 times a day intramuscularly or intravenously for 10–20 days, depending on the clinical picture and severity of the patient’s condition. Then Mexidol was taken orally at 250 mg (2 tablets) 3 times a day for up to 2 months, i.e. patients continued taking the drug on an outpatient basis.

Over time, both groups underwent a thorough neurological examination, clinical laboratory and biochemical studies (levels of sialic acids, fibrinogen, C-reactive protein), stimulation electroneuromyography (ENMG), and neuroimaging techniques (computed tomography, nuclear magnetic resonance imaging). Clinical and neurological research methods were supplemented by examining patients using scales and questionnaires: visual analogue pain scale (VAS); Roland-Morris questionnaire “Low back pain and disability”; Scale for assessing the adaptive status of patients with spinal pathology [4, 18, 22, 25]. Magnetic resonance imaging (MRI) in the supine position in the sagittal and frontal planes was performed using an “Obraz-2” apparatus (Russia) with a magnetic field strength of 0.14 Tg, a “slice” thickness of 4 mm. ENMG was performed according to standard methods [2, 3] on the Neuromian apparatus (Taganrog, Russia) to all patients with OH and 55 patients with HS. Using stimulation, the direct muscle response (M-response) was determined, the amplitude was measured in millivolts (mV) from peak to peak [3]. In addition to the amplitude, the latent period (ms) and impulse conduction velocity (ICV) were assessed. Using F-wave parameters (frequency of its occurrence, latency), the state of motor neurons and their axons in the most proximal section was assessed. The indicators of the control group (30 practically healthy people) were used as standards. Statistical processing of the obtained data was carried out using the S. Glanz program “Medical and Biological Statistics” [9].