Here you can find some materials from the Russian experience in using ozone therapy in the neurological practice incl. mechanisms of therapeutic action of ozone therapy on the pathogenetic links and main clinical symptoms of the most widespread neurological diseases as well as recommended methods of ozone therapy and expected clinical results.
Ischemic Apoplectic Attack
Ischemic apoplectic attack is a persistent focal disturbance of cerebral function caused by a "failure" of neuronal metabolism due to hypoxia. Cerebral infarction is the most severe form of ischemic brain disease. This is the main reason for stable disability of patients of neurological profile. Despite the availability of different forms and methods for rehabilitation of patients with cerebral infarction, the best result obtained is the patient's adaptation to his defect, but not its liquidation.
Nowadays, we have more knowledge about the metabolic aspects of pathokinesis of ischemic apoplectic attack. Acute cerebral ischemia induces a cascade of biochemical reactions resulting in neuronal dysfunction, astrocytosis, microglia activation, uncoordinated trophic influence (E.I. Gusev et al., 1996).
The main link of changes occurred in the neurons is considered a disturbance of energy metabolism and a sharp decrease in high-energy compounds. At the same time, this is a plain prerequisite for using ozone therapy in patients with cerebral infarction. This action of ozone is realized by inducing an increase in the oxygen utilization by cerebral cells due to the activation of glycolysis, Krebs' cycle, B-oxidation of fatty acids, on the one hand, and through its optimizing action on the oxygen-transport function of blood.
The actual problem of neuroprotection connected with a perspective of using ozone therapy in patients survived ischemic apoplectic attack remains prevention and liquidation of "excitotoxicity". One of the key mechanisms of the latter along with the activation of free-radical reactions and cytotoxine synthesis by the activated microglia is a release of excitant mediators - glutamate and aspartate into the extracellular space.
The final stage of necrotic process includes the activation of intracellular ferments, organelles destruction and intracellular edema. The described "chain" reaction can be to a certain degree limited by preparations with membrane-stabilizing effect including ozonated physiological saline within the range of ozone concentrations indicated below.
The available possibilities for rehabilitation of patients with cerebral infarction mostly depend on the state of cerebral and central hemodynamics. The correlation of these both factors of insult pathokinesis depends on the individual compensatory potential of the human body, which defines a variability of the role of hemodynamic mechanisms of disease. As "excitant" factors there are considered not only stenosis of extracranial arterial inflow and disturbances of collateral blood flow, but also a decrease in the cerebrovascular reactivity in combination with an increase in hemispheric asymmetry of vascular tonicity.
Our attention devoted to the problem of hemodynamic cerebral reserve in the given contingent of patients is connected with a great potential of "vascular" effects of ozone therapy. The restoration of kinetic activity in these patients and their return to active life mostly depends on the state of muscle tone. The potential of ozone therapy for correction of muscle tone can be connected with its positive influence on the spinal inhibitory mechanisms of pre- and postsynaptic inhibition of a-motoneurons and interneurons. The "metabolic" effects of ozone can be directed against adverse changes of blood corpuscles in patients with the given pathology.
The gathered data point out that acute ischemia is associated with enzyme activity disturbances in the erythrocytes that are responsible for intensity of transmembrane transport (ATPase). This results in an increase of Na+, Ca2+ in the erythrocytes.
An increase in the level of cholesterin and its ethers in the erythrocyte membranes leads to a disturbance of their fluidity, a decrease in the deformability. The disturbed oxidative metabolism facilitates a decrease in 2,3-diphosphoglycerate and increase in hemoglobin-oxygen affinity. According to Ya.I.Levin and A.M.Vain (1998), vegetative regulatory disorders are the key factors of cerebrovascular pathology, which leads to the more significant disturbances of vegetative control in this contingent of patients.
In this connection the vegetomodulating properties of ozone can be successfully used. The important purpose of medicamentous therapy in the acute and reparative period of ischemic apoplectic attack is an improvement of the rheological properties of blood. The characteristic pattern of shifts in the coagulation system of blood includes an increase in the adhesion and aggregation of erythrocytes and thrombocytes, in the level of fibrinogen, an increase in the hematocrit and dynamic viscosity of blood.
At the same time, the interaction between procoagulants, anticoagulants and fibrinolysis factors can lead to one of 4 types of coagulopathic reactions:
hypercoagulation of acute period;
depression of the system of physiological anticoagulants;
decompensated fibrinolytic reaction.
The correction of the given shifts includes the use of desagregants. And ozone therapy can be used as one of the methods of choice.
The problems of rehabilitation of patients with ischemic apoplectic attack are connected with secondary prophylaxis of acute cerebral ischemia. And the parameters of lipid profile, particularly content of high-density lipoproteids, are of great importance. The last-mentioned ones make a reverse transfer of cholesterin from the tissues as well as prevent thrombus formation on the plaque surface through the stabilization of prostacyclin.
This aspect of pathokinesis of ischemic apoplectic attack is extremely actual relating to the use of ozone, which selectively reacts with lipid structures.
Finally, the prospects of ozone therapy for rehabilitation of patients with ischemic apoplectic attack are also connected with immunomodulating effects of ozone, its non-specific corrective action on the processes of autoimmunization. Among the species of antibodies involved into the pathokinesis of disease there are also antibodies to phospholipids: antibodies to oxidized low-density lipoprotein, antibodies to cardiolypin.
The above-mentioned aspects of pathokinesis of cerebral infarction allow making the conclusion that there are theoretical prerequisites for using ozone therapy for rehabilitation of patients with cerebral infarction.
Recommended methods of ozone therapy:
Intravenous drop-by-drop infusions of ozonated saline solution;
Peroral intake of ozonated suspension of enterosorbent "Ensoral" in distilled water.
The performed investigations have shown that the use of the above methods of ozone therapy for rehabilitation of patients with ischemic apoplectic attack increases the efficiency of rehabilitation measures by 18-22% (including positive shifts in the motional, sensory, cognitive spheres and commonplace activity of patients).
Over 1/3 of the patients reported about the feeling of well-being already after first procedures of ozone therapy. The established positive dynamics was expressed in the decreased intensity of headache, giddiness, normalization of night sleep, stabilization of arterial pressure, improvement of appetite. The subjective feelings during the ozonated saline drip were mostly described as the feeling of "pleasant tiredness", "general comfort" Thus, the performed clinical investigations have confirmed the assumptions about the multipurpose influence of ozone therapy on the outcomes of cerebral infarction. The more effective rehabilitation treatment including ozone in the acute period has certainly the following reasons:
the more powerful adaptation potential of brain within the first weeks after ischemic apoplectic attack;
the peculiarities of sanogenetic influence of ozone therapy in this period of cerebral infarction connected with immediate correction of neuro- and haemodynamic processes of brain.
In the reparative period of ischemic apoplectic attack the accent of systemic effects of ozone therapy is shifted to the central haemodynamics that is explained by the higher elasticity of regular mechanisms controlling heart activity and arterial tone at the later stages of rehabilitation of this contingent of patients.
On the other hand, the expressed "metabolic" reactions in the oxygen-transport and coagulation systems of blood through ozone therapy are of non-specific, "basic" character manifested independently from disease duration.
In general, the rather high efficiency and absence of complications allow recommending ozone therapy as a component of complex program of rehabilitation of patients survived ischemic apoplectic attack.
Chronic Forms of Cerebrovascular Insufficiency
According to the up-to-date classification of cerebrospinal vascular diseases (E.V.Schmidt, 1985), discirculatory encephalopathy means slowly progressing cerebral circulatory disorders, which lead to gradually increasing diffuse structural changes associated with cerebral dysfunctions.
The main role in the etiology is assigned to atherosclerosis, arterial hypertension or their combination (G.A.Akimov, 1983; A.N.Baranenko, 1988; N.A.Borisova, 1995), angiocoagulopathies (E.M.Burtsev, 1978; O.N.Voskresenskaya et al, 1995), heart diseases (I.P.Gonzova, 1995; I.V.Damulin, 1995).
The insufficient oxygen brain supply and insufficient oxygen utilization characteristic of discirculatory encephalopathy are considered the main indications for including ozone therapy into the complex of therapeutic methods.
Recommended methods of ozone therapy:
Intravenous drop-by-drop infusions of ozonated saline solution or
Rectal ozone insufflations.
In order to select the patients for ozone therapy, along with disease duration it is necessary to evaluate the initial level of lipid peroxidation products and antioxidant system, their balance level as well as to control the patient's tolerance to trial single infusion of ozonated saline solution. The known contraindications should be also taken into consideration: hemorrhagic syndrome, hyperthyroidism, epilepsy, acute myocardial infarction. It is not recommended to use ozone therapy in combination with hyperbaric oxygenation to ensure neither hyperoxia nor intensified lipid peroxidation as well as with hypocoagulation preparations.
The feeling of well-being was observed practically in all patients after the first ozone treatments. This manifested in the feeling of "energy increase", "activity increase", "brain lucidity", a considerable decrease in the intensity and duration of headache, giddiness, sonitus and tiredness. After all, there were observed decreased emotional and dissomnic disturbances, absent-mindedness, increased interest in the environment (communication, books, TV programs), improved memory (A.A.Smirnov, 1996).
So, the use of ozonated saline drips as a component of multimodality therapy of patients with discirculatory encephalopathy associated with atherosclerosis of cerebral blood vessels or in combination with arterial hypertension has shown that along with clinical improvement it comes to positive shifts in the structure of lipid metabolism parameters. The investigation into the lipid peroxidation products and antioxidant system in dynamics before and after the treatment has shown a reliable decrease in diene and triene conjugates in patients at I and II stages, and in Schiff's bases - in patients at all stages of discirculatory encephalopathy. At the same time, it comes to a significant activation of the antioxidant system as an increase in blood enzymes: superoxidedismutase at all stages and catalase at I stage that points out a stimulation of the organism's defense potential in the conditions of chronic hypoxia associated with discirculatory disorders.
The analysis of immediate results of treatment including ozone therapy has established that the efficiency of treatment is higher in patients with discirculatory encephalopathy of I and II stages associated with atherosclerosis of cerebral blood vessels with disease duration less than 10 years. A good effect owing to the use of ozonated saline solution is received in patients at I stage associated with hypertensive disease. There is no direct relationship of the results of treatment with the course of discirculatory encephalopathy, age and associated diseases. Only insignificant improvement after the course of treatment including ozone therapy is found out in patients with discirculatory encephalopathy of II and III stages associated with atherosclerosis in combination with hypertensive disease of II-III degree. There are no deteriorations of the patient's state and side effects due to intravenous ozone therapy. The received results allow making a conclusion that the more expressed and stable clinical improvement in patients with discirculatory encephalopathy is connected with the use of ozonated saline drips which can be explained by its action on the main pathogenetic mechanisms of discirculatory encephalopathy.
So, the use of ozone facilitates to level the changed values of lipid metabolism, to activate the enzymatic link of antioxidant defense system by inducing a decrease in the level of initially increased lipid peroxidation products. After all, a decrease in the blood viscosity allows improving the rheological properties of blood and therefore decreasing hypoxia appearances in central nervous system that along with a decrease in angiospasm symptoms contributes to the improvement of cerebral haemodynamics parameters, according to REG.
Basing on the above-mentioned, the general mechanisms of action of ozone therapy in chronic ischemic disturbances of cerebral circulation can be demonstrated as follows:
The use of ozonated saline drips results in the production of the so-called ozonides in the patient's blood. These secondary compounds of ozone are transported through the whole body. In consideration of the intensity of cerebral blood flow, most of the ozonides penetrate through the haematoencephalic barrier into the brain where producing a membrane-stabilizing effect through the improvement of structural-functional properties of neuronal membrane lipid biolayer. Cell membranes are the main targets of action of ozone on the body systems. This results in the improvement in the processes of transmission, processing and keeping of information in CNS (A.N.Erin, N.V.Gulyaeva, E.V.Nikushin, 1994).
On this basis the optimization of integrative activity of brain takes place that results in the more fast development of compensative processes with improvement or restoration of sensorimotor, limbic-reticular functions and others.
So, the results of the conducted investigation allow recommending the given method of complex treatment with ozonated saline drips as a pathogenetically adequate method of treatment for patients with discirculatory encephalopathy associated with atherosclerosis and arterial hypertension.
The investigation included 68 patients: most of them had migraine without aura (64%); migraine with aura was diagnosed in 36% of cases. In the structure of aura visual disturbances and paresthesia were dominant. One patient had ophtalmoplegic migraine.
Average age of patients was 26,3 years. The women predominated over the men (71%). The frequency of migraine attack ranged from 2-3 per week to 5-6 per year. Most of the cases showed one-sided character of headache (73% of the investigated patients). In 32% of the patients paroxysms were associated with tension headache in the interictal period.
Ozone therapy was included into the complex treatment of 50 patients of the main (experimental) group.
Recommended methods of ozone therapy:
Intravenous drop-by-drop infusions of ozonated saline solution.
Along with neurological status, the results of treatment were evaluated on the basis of thorough examination of patients including the investigation into the cerebral neurodynamics, haemodynamics, vegetative regulation of heart rhythm, intensity of headache, anxiety, lipid peroxidation processes, antioxidant activity of blood plasma.
The results of dynamic observation have shown that the use of ozonated saline drips as a component of complex treatment increases its efficiency by 29%. The number of discharged patients with good therapeutic effect in main group (87%) was reliably higher than in control group (61%, p<0,05). The absence of non-responders among the patients received ozone therapy allows considering the latter as a reliable method of preventing resistance to the provided therapy in this contingent of patients.
Ozonated saline drips used in the interictal period ensured in 58% of the patients no migraine paroxysms within 4 to 8 months (in average 6,2 months) after their discharge from hospital. In other 19% of the patients the duration of attackless interval was limited to 3 months. However, after repeated migraine attacks, the frequency of attacks and intensity of headache were considerably less (on average 4,3+ 0,31 points according to the visual analog scale) than before the treatment.
The experience in the use of ozonated saline drips during the migraine paroxysm points out a clear correlation between the time from the beginning of headache to the point when ozone therapy was performed and its efficiency. As sooner the procedure was performed as less intensive was headache in further.
Basing on the received results it is obvious that the use of ozonated saline drips both as a component of complex treatment and as a monotherapy allows achieving a stable clinical effect in a relatively short time. The performance of repeated courses of ozone therapy with frequency 2-3 times per year allows to improve considerably the life quality of patients with migraine, significantly reduce the time of their disability.
The use of the above-mentioned methods of ozone therapy is more effective in the interictal period, but the method of ozonated saline drips can be included into the list of basic measures used for stopping migraine attack.
The efficiency of ozone therapy in the given contingent of patients was connected with the influence of the secondary products of ozone on the key pathogenetic mechanisms. The improvement of conditions for neuron's membrane function, normalization of rheological properties of blood through ozone therapy can be successfully added to immediate analgesic effect of ozonated saline drips through the interference of basic mediators of noci- and antinociceptive brain systems into the metabolism.
Disseminated sclerosis is numbered to the group of demyelinating diseases of nervous system and characterized by the young contingent of patients, peculiar epidemiology and pathomorphology, difficulty in diagnosis and treatment.
The essence of disease is not limited by the formation of sclerotic plaques. The pathological process also involves immune system, different sides of metabolism, structures of vegetative nervous system (V.A.Karlov, 1990: E.I.Gusev et al., 1997; B.T.Haidarov, 1998).
According to most of the investigators devoted to this problem, disseminated sclerosis is a virus-induced disease. The leading role belongs to measles virus. The genetical determination of this disease is proven.
The complicacy of polysystemic, multi-level disturbances developed in this disease allows to determine some sanogenetic targets for efficient use of ozone therapy:
immunocorrection with accent on the cellular link of immunity;
"leveling" of genetically determined and secondary developed disturbances of intracellular neurons' metabolism;
stabilization of myelin as biological membrane;
normalization of biochemical parameters and gas composition of blood;
restoration of "trophic control" on the part of vegetative nervous system.
The clinical investigation included 67 patients with disseminated sclerosis and 15 volunteers. Age of the investigated patients ranged from 19 to 49 years. Among the patients there were 39 women and 28 men. Average duration of disease was 3,8 years.
All the investigated patients were divided into 4 groups: 2 main (test) and 2 control (placebo). The treatment of patients of the 1st main group (n=22) along with standard therapeutic complex (prednisolon 30-60 mg/24 hrs, vitamins B, C, E, phytin, curantyl, ATP, T-activin, nootropil) included intravenous infusions of ozonated saline solution with ozone concentration. The patients of the 2nd main group (n=23) along with the above-mentioned standard treatment received ozone therapy in the form of intravenous infusions of ozonated saline solution in combination with per os intake of ozonated suspension of enterosorbent "Ensoral" in distilled water. This schema of treatment was based on the evidence about the efficiency of enterosorbents for patients with disseminated sclerosis as well as on the assumption about possible mutual potentiation of detoxication and immunomodulating effects of ozone and enterosorbents used in combination. And the great area of sorbing surface of "Ensoral" with structure C - C - C - C was considered a prerequisite for a certain "depot" of ozone within the whole gastroenteric tract. The selected ozone concentration is usually used for enteral methods of ozone therapy.
The received results have shown that the second variant of multimodality therapy has proved to be the most effective in the treatment of patients with disseminated sclerosis. The use of the above-mentioned treatment schema facilitated a decrease in the resistance to the performed therapy though the decrease in non-responders; prevention of increased deficit of T-lymphocytes (particularly T-suppressors) connected with the use of glucocorticoide hormones (parallel to regression of B-lymphocytes); normalization of vegetative tone in the cardiovascular system; increase in the transmission rate of nervous impulses through peripheral nerves.
Compressive Ischemic Neuropathies
Tunnel compressive ischemic neuropathy is a pathology of nerve trunk caused by its local irritation, compression and ischemia in anatomically and biochemically adverse conditions of nerve location (V.S.Lobzin, A.F.Rahimdzanov, N.M.Zhulev, 1988). This definition alone makes it clear that compressive ischemic neuropathy (CIN) is a polyetiologic disease. Considering the leading role of nerve trunk ischemia in the pathogenesis of CIN, for improvement of blood circulation, oxygen supply and function of compressed nerves it is advisable to use ozone therapy.
Recommended methods of ozone therapy:
Intravenous drop-by-drop infusions of ozonated saline solution.
Positive clinical results were received in 95% of cases with ozone therapy as a significant decrease in complaints, normalization of provocative tests, improvement of sensitivity in the zone of innervation of affected nerve. Owing to the considerable decrease or disappearance of night paresthesia of hands after the course of ozone therapy, it comes to normalization of night sleep, improvement of general state, increase in workability. Ozone therapy in the form of ozonated saline drips didn't cause any deterioration of the patients' state, side effects or complications (Yu.P.Potehina, 1997).
The improvement came as a rule after 3-6 procedures. After all, at the end of one course of ozone therapy the inhibition of lipid peroxidation processes and activation of antioxidant activity took place according to the data of biochemiluminescence analysis of blood plasma and determination of lipid peroxidation products.
The achieved results of treatment kept on average for 7 months. So, it is recommended to provide the patients with compressive ischemic neuropathies prophylactic courses of ozone therapy including 5-12 ozonated saline drips every two days, two times per year, in spring and autumn.
Summarizing the investigated and well-known mechanisms of action of ozone, ozone therapy in the form of ozonated saline drips is involved into the pathogenesis of compressive ischemic neuropathies at several stages:
Parenteral ozone therapy facilitates an increase in the partial oxygen pressure of arterial blood through the oxygen saturation of both plasma and erythrocyte hemoglobin (R.Chiong et al., 1990), which can induce a decrease in both general and local tissue hypoxia, activation of gas metabolism in the zone of ischemia.
Ozone is able to stimulate glucose metabolism in the erythrocytes, formation of 2,3-diphosphoglycerate - substance contributing to the more complete oxygen release by oxyhemoglobin and shift of oxyhemoglobin dissociation curve to the right (O.Rokitansky, 1982). Thus, more oxygen is released to the tissues, particularly affected by ischemia.
Owing to the interaction with corpuscle membrane lipids, ozone increases the deformability of the erythrocytes and decreases their aggregation and thus improves fluidity of blood in micro flow bed.
The ozonated saline drips improve peripheral blood circulation through the elimination of arteriolar spasm, increasing pulse blood filling and improving venous blood outflow to the limbs. Ozone can facilitate a decrease in arteriolar spasm and opening of non-functional capillaries thus activating microcirculation in the ischemized tissues.
Ozone used in therapeutic doses moderately decreases blood coagulation by shifting the values of coagulogram to the bottom level of norm, particularly in cases of initial tendency to hypercoagulation. This can help to decrease or prevent intravascular coagulation of blood, particularly in case of venous stagnation and ischemia. By inducing moderate hypocoagulation in the form of increase of activated recalcification time and activated thromboplastin time, decrease of platelet aggregation and activation of fibrinolysis, ozone is able to prevent thrombosis at the areas of decelerated blood flow and facilitates the lysis of produced small thromboses thus improving the rheological properties of blood.
Thanks to the improved blood circulation, particularly in micro flow bed, ozone possibly decreases tissue edema and tissue tension in the canal.
Thus, ozone actively involved into the pathogenesis of compressive ischemic neuropathies stimulates the restoration of affected nerve primarily through the improvement of microcirculation and rheology of blood. Ozone therapy without eliminating the main causes of nerve trunk compression decreases hypoxia and activates oxygen metabolism in the ischemized tissues. Such a pathogenetic action of ozonated isotonic solution is very important for nervous tissue where only aerobic processes can take place.
Ozone used by parenteral route can directly or indirectly influence on some mechanisms of formation of compressive ischemic neuropathies and at the same time break "adverse circles" of pathogenesis as well as optimize oxygen homeostasis in the compressed nerve trunk.
Neurological Appearances of Spinal Osteochondrosis
Spinal osteochondrosis is considered a chronic systemic disease of connective tissue which development requires genetic disposition and manifestation - exposure to exo- and endogenous factors. Among the first ones there are numbered physical, chemical and infectious agents, and among the second ones - certain constitutional variants, spinal anomalies, peculiar function of motional system, associated diseases of spine and other organs (V.P.Veselovsky, 1991).
This multi-factor disease first affects intervertebral disc and then other sections of locomotor apparatus and nervous system (O.G.Kogan et al., 1983).
Among the neurological appearances of spinal osteochondrosis vertebrogenic pain syndrome is of greatest importance for adequate evaluation of efficiency of the treatment performed. This syndrome consists of 4 components: muscle pain, fascial-ligamentous pain, joint pain, discogenic pain.
According to the above-mentioned, the conservative treatment of patients with neurological appearances of spinal osteochondrosis should be complex, differential and based on the main pathogenetic mechanisms of disease. The therapeutic measures should be focused on both the vertebral area of affection and extravertebral appearances.
There are 5 main principles of therapy for vertebrogenic diseases of nervous system:
exclusion of adverse static-dynamic loads;
stimulation of muscle corset;
phase and complete exposure;
decrease in pain feelings;
careful character of therapeutic measures.
The latter 4 principles can be fully realized by methods of regional (local) ozone therapy specially developed for neurological appearances of cervical and lumbar osteochondrosis.
Recommended methods of regional (local) ozone therapy:
Minor autohaemotherapy with ozone;
Paravertebral ozone injections;
Subcutaneous ozone injections into the biologically active points;
Intramuscular ozone injections into the trigger points.
Ozone therapy was used within the complex treatment including non-steroid anti-inflammatory medicines, vitamins of B group, sedative preparations, therapeutic exercises.
The approximate schema of sanogenetic reactions developed in patients with neurological appearances of spinal osteochondrosis through regional ozone therapy includes:
Decrease in the irritation of sinuvertebral nerve ends due to the decreased action of:
a) the discirculatory factor, a decrease in the edema of surrounding tissues;
b) the dislocation factor due to partial restoration of amortization properties of the affected disc, as a result, improvement of its metabolism and activation of trophic influences;
c) the aseptic-inflammatory factor induced by the synthesis of prostaglandins as inflammation mediators and activation of cellular immunity contributing to fast elimination of "foreign" components. As a result, it comes to a significant decrease in afferent flow from periphery to CNS.
Actual antinociceptive action of ozone therapy connected with:
a) direct oxidation of algopeptides;
b) a decrease in underoxidated products in spasmodic muscles;
c) an increase in excitability threshold of pain receptor membranes (membrane-stabilizing effect).
3. Improvement in the function of spinal segmental apparatus manifested as:
a) acceleration of formation of a new motional stereotype;
b) activation of spinal mechanisms of pain control;
c) normalization of vegetative-trophic basis of motional act.
The above-mentioned can be considered a substitution for the use of regional ozone therapy in the complex treatment of patients with neurological appearances of spinal osteochondrosis.