Method of treating spasticity accompanied by improved consciousness in patients in vegetative state
SUBSTANCE: invention refers to medicine, namely to neurology, and may be used for treating spasticity accompanied by improved consciousness in the patients in the vegetative state. That is ensured by administering Xeomin (botulinumtoxinA free from complexing proteins) into the spastic muscles of all the extremities and related body segments regardless of the contractions in total dose of 400-1300 units. The dose shall not exceed 24 unit/kg of body weight in 1-3 stages. The stages follow at least every 3 days. Every 1-day stage involves administering 5-50 units in each accessible muscle or muscle group with the maximum tone in max. total dose 500 units dissolved in 12.5 unit/ml. The injections are distributed uniformly along the area without electromyography. The following courses are similar if observing spasticity and/or if clinically reasonable. The length of one course is up to 3 weeks.
EFFECT: method enables improving the therapeutic effect in the vegetative states.
3 ex, 3 tbl
The invention relates to medicine, namely neurophysiology, neurology, neurosurgery, neurotraumatology and can be used to reduce spasticity and improve consciousness in patients in a vegetative state and on the way out, as well as for the treatment of spasticity in other categories of patients with diseases of the Central nervous system (CNS).
Severe lesions and diseases of the Central nervous system may be accompanied by impaired consciousness, coma, followed by the transition into a vegetative state and small consciousness. When a vegetative state or a small consciousness due to gross morpho-anatomical and/or functional disorders of various brain structures is often observed coarse increased tone of skeletal muscles. This is usually generalized or multifocal spasticity with symptoms of spastic dystonia, abnormal attitudes and postures of the limbs and body, and sometimes the neck and head, development of contractures and deformities in the "interested" joints.
In clinical practice, the need for treatment of spasticity in patients in a vegetative state and small consciousness is determined primarily by care, at least - minimize debilitating musculoskeletal disorders (in the case of an alleged recovery of consciousness). However, spasticity nutrition which is expressed pain syndrome, and roughly increased muscle tone can lead to the violation of hemo - and liquorices, which further exacerbates brain damage.
Existing methods of reducing spasticity and methods aimed at restoring consciousness of patients in a vegetative state, are empirical. When applying these methods to their "separately," they are often not effective, and if a joint application is often incompatible or nullify the action of each other.
Treating patients in a prolonged unconscious state, based on the teachings N.P. Bechtereva, we were able to show that vegetative state should be considered as a stable pathological condition (STS) brain (I.E. severe). The exit of the patient from the vegetative state is implemented when the imbalance oops. To visualize the functional state of the brain changes when the imbalance oops using PET with 18 F desoxyglucose.
At UPS broken multifunctional neurons (the neurons to perform various activities (I.E. severe)). This plays a significant role pathological sverhzaprosy neurons, developing, including, due to pathological Hyper - and efferently associated with spasticity of skeletal muscles. On this basis, patients in vegetative the m state, the reduction of spasticity directly "in the muscle" (without effect on neurons of the Central nervous system, under COC), indirectly improves the functional state of neurons in the Central nervous system and appears to improve consciousness.
There is a method of treating spasticity by various methods of physiotherapy, physiotherapy, reflexology, (Belova A.N., Prokopenko SV Neurorehabilitation. // 3rd ed., revised and enlarged additional Meters: the Antidoron. 2010. 1288). However, in patients in a vegetative state, they are not effective, they are usually used as an additional therapeutic effects (in combination with other methods of treating spasticity, see below). Transcranial electrostimulation in some cases may affect the level of consciousness of patients, however, patients in a vegetative state it is contraindicated because of the presence of epileptic seizures or high risk of their development, the method used in extrapyramidal syndromes (rigidity, ticks).
There is a method of treating spasticity by medical treatment with the use of pharmacological preparations of different pharmacological groups (clonazepam, sirdalud, baclofen, midokalm, dantrolene) separately and in various combinations (Gusev E.I., Geht A.B. Spasticity // Rus. The honey. Zhurn., 1999 Vol.7. No. 12. S-571). The method is often used in patients in a vegetative state. However these drugs in generalized and rough hypertonicity of the muscles in the mid-therapeutics is their doses are often not effective, and in large doses, cause a number of side effects. So, the side effect of muscle, lower blood pressure, leads to impaired perfusion of the brain. This exacerbates impairment of consciousness and induces the posture-tone responses. Often when a vegetative state is observed resistance is "addictive" or insensitivity or pathological reaction to these drugs.
Known methods of treating spasticity by operations on spinal cord: myelotomy, rear selective rhizotomy, installation baklofenbuy pump and further chronic intrathecal introduction baclofen, chronic electrical stimulation of the spinal cord. (Shabalov, V.A. et al. The possibility of chronic electrical stimulation of the spinal cord in the treatment of spastic syndrome // .First International Scientific Distance Congress on Spine and Spinal Cord Surgery "InterSpine - 2004", SPb, Russia, September, 2004., C.44-45). The methods typically used to reduce spasticity in the legs. After myelotomy the restoration movement is not possible. With regard to the drug resistance to baclofen setting baklofenbuy pump may be ineffective in patients in a vegetative state. Operation high-tech, traumatic, possible septic complications, liquorrhea.
There is a method of treating spasticity, rigidity and hyperkinesis by surgical is th (stereotactic) operations on the brain with therapeutic or deep stimulation or destruction of various morpho-anatomical brain structures in various modifications (Smirnov V.M. Stereotactic neurology // HP: "Medicine". 1976. S.) The method allows for the impact on certain centers in the brain to reduce muscle hypertonicity and in some cases to improve consciousness and communicative activity patients. However, the method is invasive, requires surgery on the brain, in some versions - the use of implanted electrodes, may be accompanied by inflammatory and traumatic complications, costly, high-tech, designed primarily for individual diseases of the extrapyramidal system.
A known method of surgical treatment of spasticity by selective operation of neurotomy, which consists in the surgical intersection of motor nerves (Umnov CENTURIES, Kenis V.M. Neuroactivity approach to the correction of contractures in patients with spastic paralysis // Traumatology and Orthopaedics, Russia, 2009, 1(51) P.55-60). Reduces spasticity at the level of individual limb segments. Designed for cerebral palsy. Operation high-tech, traumatic, possible purulent-septic complications.
There is a method of treating spasticity by repeated courses of botulinum toxin therapy to improve self-service after stroke (O'brien c.f.nielsen (Denmark) Injection techniques for botulinum toxin using electromyography and electrical stimulation // Muscle and Nerve. 1997. Vol.20. P.176-180.). 3a one course of botulinum toxin therapy, with the standing one step introductions, allowed to use the drug botulinum toxin injected into the muscles with maximum tone, but not formed contracture (usually the introduction is carried out in the arm) and is safe for injection. Injections in the muscle exercise in General for botulinum rules using electromyography (EMG). The total dose of botulinum toxin for the course does not exceed 400 UNITS of Botox (or another drug comparable doses). Repeated courses a few months, with increasing spasticity. When multifocal, generalized spasticity from contracture is not applicable.
There is a method of treating spasticity in patients in a vegetative state by repeated courses of botulinum toxin therapy using the drug botulinum toxin a, free from complexing proteins (Xeomin) and conducted to facilitate care and local pain reduction. For the first year of botulinum toxin therapy, consisting of one stage introductions, Xeomin injected in one limb, which are maximally expressed: muscle hypertonicity with pathological posture and contracture, and spastic muscles other limbs left intact. Xeomin enter in the breeding of 25 IU/ml using EMG and on the General rules of introduction of preparations of botulinum toxin in skeletal muscle in the total course dose of no more than 400 IU. The trail is the following courses of botulinum toxin therapy is carried out through 4, 6 and 10 months and implement the introduction of the same muscles, as well as in spastic muscles another limb on clinical need, while the total dose of leave or still lower.(M. Bonse in the book. R. Laskawy, T. Vogt Botulinum toxin type a, a practical guide // M "Medpress-inform". - 2012., P.58-63). Adopted for the prototype.
The method allows to effectively reduce muscle tone in one limb or its segments with decreasing abnormal postures in it. Does not require the appointment of additional medication to normalize muscle tone in injectable muscle when choosing optimally effective dose. Has a local (in accordance with injections) analgesic effect. Simple and accessible, it is possible to introduce into any available skeletal muscle. Well tolerated, there are no systemic side effects. Secure the immune complications, because the preparation is used, free from complexing proteins (Xeomin).
The disadvantages of the method chosen for the prototype:
1. Not effective to reduce hypertonicity all spastic muscles in generalized and multifocal spasticity. This requires additional medication and/or other method for the treatment of spasticity.
2. For the same reason is not effective to stop the pain apperentice is all spastic muscles, that also requires additional treatment.
3. According to claim 1. and item 2 does not terminate pathological Hyper AF and efferently and therefore does not improve the level of consciousness in patients in a vegetative state.
4. Does not prevent the development of contractures, because the introduction is carried out in a limb contractures, and leave the rest intact.
5. The method does not allow to select effective and sufficient dose of Xeomin for the reduction of muscle tone in injectable muscle, because the introduction is conducted in one step and without taking into account individual sensitivity.
6. Do not run if necessary suddenly to interrupt the introduction of Xeomin, for example, in the development of an epileptic seizure, or other typical vegetative state syndromes, because the method does not allow an "extended" introduction.
7. Limited to a total dose of 400 IU of Xeomin, at this dose effectively reduces spasticity of one hand, not effective enough for legs and not effective in spastic tetraparesis.
8. For use of Xeomin in a dilution of 25 IU/ml, which determines the maximum search spastic stretch the muscles.
9. To identify the spastic muscles and most spastic plots used EMG. Using EMG, in addition to additional equipment, provides additional diagnostician is ical intramuscular injection, a needle and electrical irritation of the muscles. This increases the trauma, can reduce therapeutic effect, while the diagnostic value of research at rough spasticity is not justified.
10. Established the terms of the following courses of botulinum toxin therapy, but their clinical necessity not specified.
The technical result of the proposed solution is to increase the effectiveness of treatment of spasticity in patients in a vegetative state by repeated courses of botulinum toxin therapy using the drug botulinum toxin a, free from complexing proteins (Xeomin) and the improvement of the mind through the phased introduction of Xeomin in a large total dose and in a large dilution in all spastic muscles of the limbs and accompanying body segments without EMG. This leads to a gradual decrease in all pathological Hyper AF and efferently associated with spasticity, and, consequently, to improve the level of consciousness of patients in a vegetative state.
Technical result is achieved by the fact that during the course, lasting up to 3 weeks, Xeomin injected into spastic muscles of all limbs and accompanying body segments regardless of contractures in a total dose of 400-1300 UNITS not exceeding 24 UNITS/kg of body weight for 1 -3 phase, which is carried out with an interval of not less than 3 days, with each stage lasting up to 1 day is it in every available muscle or muscle group with a maximum tone enter 5-50 UNITS in a total dose of not more than 500 UNITS, in the breeding of 12.5 IU/ml by the uniform distribution of the injection area muscles without EMG, the following courses are conducted similarly to the case of increasing spasticity and/or clinical need.
The essence of the invention is expressed in a set of key characteristics, sufficient to achieve provided by the invention a technical result.
The essential features of the proposed method of treatment, coinciding with the characteristics of the prototype are:
- introduction of the drug botulinum toxin a purified from complexing proteins (Xeomin)
- the introduction is carried out in spastic muscles
- repeat courses of botulinum toxin therapy.
Salient features are:
- a course of botulinum toxin therapy, lasting up to 3 weeks,
over the course Xeomin injected into spastic muscles of all limbs and accompanying body segments regardless of contractures,
- total dose rate 400-1300 UNITS does not exceed 24 UNITS /kg of body weight
the course consists of 1-3 stages of injections, which are conducted at intervals of not less than 3 days,
at each of the stages up to 1 day in every available muscle or muscle group with a maximum tone enter 5-50 UNITS in a total dose of not more than 500 UNITS,
in breeding of 12.5 IU/ml by the uniform distribution of the injection area the mouse is s without EMG,
- the following courses of treatment carried out similarly with an increase in spasticity and/or clinical need.
A method of treating spasticity accompanied by improvement of consciousness in patients in a vegetative state as follows. According to the instructions carried out breeding Xeomin: in a bottle of Xeomin 100 U add 8 ml of physiological solution (solvent) and receive 12.5 U/ml Storage Xeomin vial diluted valid up to 24 hours at a temperature of from +8 to +2 With gr. Trying to enter the solution in the syringe.
Before each stage of introduction conduct a physical examination of the patient, and determine the hypertonicity of the muscles of the arms and chest muscles, shoulder girdle and neck included in the formation of abnormal postures; leg muscles and muscles of the pelvis and buttocks, are included in the formation of abnormal postures. Among them, define muscles and muscle groups that are available for injection and having at the time of inspection the maximum tone regardless of contractures: they held the stage, the introduction of Xeomin.
In each of the specified muscle or muscle group is injected at 5-50 ED Xeomin. The dose is determined by the size of injectable muscle, the severity of hypertonicity, individual sensitivity. The total dose for the phase is not more than 500 UNITS. Injections are carried out in compliance with the rules of asepsis and antisepsis for each injection use their sterile injection needle. Xeomin in the specified dilution injected without the use of EMG, by distributing the injection area of the muscle. If necessary the introduction of one stage can be carried out during the day.
The following stages are carried out similarly, choosing for injection is available muscle or muscle group with a maximum tone at the appropriate stage. Over the course Xeomin enter all spastic muscles or muscle groups and muscles with the most serious tone - by re-introductions.
The number of required stages for the course (1-3), the intervals between the stages is not less than 3 days (on day 4 and below) are set individually depending on the severity of spasticity, abnormal postures, contractures, and individual sensitivity. The total duration of the course up to 3 weeks. The total dose rate 400-1300 UNITS, does not exceed 24 UNITS/kg of body weight of the patient. The following treatments likewise, when the increase spasticity and/or clinical need.
Xeomin. is the lyophilisate for solution for intramuscular injection in a vial containing: botulinum toxin type a (BTA) - 100 UNITS, sucrose - 4,7 mg, serum albumin human 1 mg
The main point of application of BTA - presynaptic terminal cholinergic synapses. In the zone of injection of the toxin blocks the release and is milholin from the presynaptic terminala axon by splitting synaptosomal transport proteins (type blocks And SNAP-25). Intramuscular injection of botulinum toxin develop two effects: a direct inhibition of alpha motoneurons at the level of the neuromuscular synapse and inhibition of gamma-motoneurones cholinergic synapse on intrafusal fiber. Reduced gamma activity leads to relaxation intrafusal fibers of the muscle spindle and reduces the activity of 1A-afferents. This leads to reduced activity as muscle stretch receptors and efferent activity of alpha - and gamma-motoneurons. Clinically, this manifests itself in a pronounced relaxation of the injected muscles and significant reduction of pain in them. Analytical effect appears earlier and lasts longer than myorelaxation. Reduction of pain can occur in the absence of muscle relaxant effect
Xeomin has better properties in comparison with other drugs BTA (Botox, Dysport and other), as purified from complexing proteins (Dressier D. Five-year experience with incobotulnumtoxinA (Xeomin(®)):the first botulinum toxin drug free of complexing proteins // Eur J Neurol. - 2011. - V.19(3). - P.385-9.). Xeomin minimum molecular weight components (150 KD), compared to Botox - 900 KD. This determines the minimum the risk of developing antibodies, insensitivity and side effects when using Xeomin (Rustavi, Tbogt Botulinum toxin type a, a practical guide IIM. "Maddie the with-inform". - 2012. - 103).
The units of activity (U) Xeomin and Botox are equivalent when comparing the LD 50 of the differences between drugs are not observed (Dressier D., Mander G.J. K. Fink Equivalent potency of Xeomin and Botox. // Toxicon.2008.- V.51 (S.1): 10). One unit corresponds to the LD50 for female mice Swiss-Webster weighing 18-20 toxicwaste (LD50) for monkeys is in intramuscular - 39 IU/kg intravenous - 40 U/kg (CIT.: All To the question of botulinum toxin therapy for post-stroke spastic paresis: mechanisms of action of botulinum toxin, the algorithm rehabilitation treatment // Leche. doctor. 2012. No. 2).
Botox was used in high doses 474,7+-167,1 ED and high doses (up to 840 UNITS) in 37 patients with this system and toxic side effects were not. In similar doses Xeomin also did not cause systemic and toxic effects. (Dressier D, Adib Saberi F. First high dose use of complex free botulinum toxin type All Mov Disord 2006, 21 (S.15). - S.640).
According to histology: 30 repeated injections in the same muscle does not cause irreversible dinnerware and atrophy (CIT.: Korolev A.A. To the question of botulinum toxin therapy for post-stroke spastic paresis: mechanisms of action of botulinum toxin, the algorithm rehabilitation treatment // Leche. doctor. 2012. No. 2).
Engineering (General rules) injection of botulinum toxin into the muscles known: defined injecting access to a muscle is, the optimal number of injections in each arm, and the range of doses of botulinum toxin for each muscle in accordance with the size of the muscle and the degree of hypertonicity (Wolfgang Jost / Pictorial Atlas of Botulinum Toxin Injection, UK, Quintessence books, 2008, c.103).
The inventive method is developed and clinically tested in IMC wounds in the treatment of 14 patients in a vegetative state different etiology (open and closed craniocerebral trauma, hypoxia and toxic brain damage) with coarse generalized and multifocal spasticity, abnormal postures and contractures. All patients spasticity of the muscles was pharmacoresistant (applied medical treatments were not effective or had a clinically significant side effects). During treatment, patients were kept under observation in the Department of anesthesiology and intensive care IMC wounds. To assess spasticity used a modified scale Ashworth (A. Belov. Tests, scales and questionnaires in neurology and neurosurgery. // Moscow, 2004 - 432 (C), for the assessment of neurological status (consciousness and communicative activity) - Loewenstein Communication Scale (Borer-Alafi N., Gil M., Sazbon L., Korn C, Loewenstein Communication Scale for the minimally responsive patients. - 2002. - V.16, N 7. - P. 593-609.), for neuroimaging assessment of the functional state of the brain positron emission tomography (PET) with 18F-Tordesillas. These studied what I had been immediately before the treatment and after 2-3 weeks after. During the course of treatment and up to the control of complex surveys, long-term patients receive therapy was not changed, a different treatment was not performed.
In clinical trials were of superior quality and results of treatment of vegetative state. First, was reduced generalized, multifocal muscles spasticity and associated pain apperentice and trophic disorders; improved (appeared) movement in the joints, made easier care. Secondly, improved consciousness and communicative activity with patients.
While there was an improvement in neurological symptoms from neurons, providing a variety of motor, visual, auditory, and higher mental functions, as well as changes of glucose metabolism in relevant areas of the brain (PET).
Example 1. and/b 703 -2012
Patient M., 23 years. Postanoxic vegetative state (later of clinical death due to electric shock).
In the case of hospitalization IMC RAS: vegetative state for 2 years, 17 points (b.) on LCS. Syndrome musculoskeletal disorders (spastic quadriplegia (spasticity 5 b. on mod. SHK. Ashworth), abnormal posture, contracture and deformity of large and small joints). Pseudobulbar syndrome. Epileptic syndrome.
Neurodystrophic syndrome. Cachexia. The gastrostomy tube. X is onionskin inflammatory diseases of internal organs. Weight 54 kg
Attempts neurovasculature therapy aimed at restoring consciousness, drug-induced reduction of spasticity have been tried, but are not effective for 2 years in a vegetative state.
The treatment according to the method prototype is not applicable, because the severity of spasticity, the symmetric nature of the pathological postures and contractures are not allowed to identify the most affected limb.
Conducted 1 treatment, see table 1. Xeomin introduced in a total dose of 1300 UNITS (24 UNITS/kg of body weight). At the first stage of injection is performed in the muscles that are available for the introduction of the next phases in the rest, where the opportunity arose to be injected and repeated injection in the same muscles as needed. Side effects were noted.
Dynamics of three weeks from the start of treatment:
1. Reducing spasticity from 56 to 2 b. on mod. SHK. Ashworth appeared minimal passive movements of joints with contractures and decreased significantly abnormal posture, regressed trophic disorders
2. Improvement in LCS from 17 to 32 points:
- mobility (+6 b.): improved overall motor response, turns head and eyes, appeared yawning, swallowing, facial expressions, tears; visual-reactivity (+5 is.): the sight was awakened, aimed at the surrounding, normal blink reflex, began to focus his eyes appeared selective tracing;
- auditory perception (+3 b.): appeared, reaction to noise, voice, and attempt to execute a simple command.
- verbal communication (+1 b.): appeared articulation
3. According to PAT: relative increase energy metabolism in the cerebellum and the brain stem (an increase of 17%).
In the future, for 5 months of observation spasticity is not growing.
Psycho-neurological status with positive dynamics.
Thus, the treatment under the proposed method has improved the awareness and to reduce generalized spasticity in patients 2 years were in a vegetative state, resistant to treatment.
Example 2. Patient K., 38, and/b 378
Post-traumatic vegetative state (the Consequence of concomitant severe closed traumatic brain injury, fracture of the left tibia). Syndrome musculoskeletal disorders (generalized spasticity, abnormal posture, initial contractures of the metacarpophalangeal and interphalangeal joints). Pseudobulbar and bulbar syndrome. Neurodystrophic syndrome. Cachexia. Chronic inflammatory diseases of internal organs.
According to the medical history: medication attempts recovery of consciousness is not what effectivny. Medication spasticity was accompanied by a decrease in blood pressure and discontinued.
Treatment according to the method prototype, conducted injections Xeomin (400 IU) in spastic muscles of the right leg with a positive effect 4 months, but the level of consciousness has not changed.
When entering IMC RAS: Weight of the patient - 42 kg Level of consciousness and communicative activity - 8 b. on LCS., spasticity in the hands - 4-5 B., in the left leg - 3-4 B., in the right foot-3-4 b.
The stages of treatment - see table 2. Put 800 IU of Xeomin (19 IU/kg body weight). At each stage involved the introduction of the muscle with the highest tone. Re-introduction in muscle was not required. Side effects and complications was not.
As a result of treatment for three weeks of observation:
1. Reduction of spasticity with 3-5 to 1-2 b. on mod. SHK. Ashworth
2. Improvement in LCS from 8 to 20 b.
- mobility (+7 b.): improvement of motor responses, there were attempts movements of the limbs, turning the head and eyes, the elements of swallowing;
visual - reactivity (+4 b.): the sight was awake, appeared blink reflex, periodically captures the view, trying to track; -auditory perception (+1 b.): reaction to the voice, try to execute the command.
3. According to PAT: the relative increase in energy is of metabolism in the cerebellum and the brain stem 16%.
Further, the positive dynamics of the psycho-neurological status was maintained. For the 6 months observation spasticity has not increased. Thus, the treatment by the present method has allowed to reduce generalized spasticity and to improve the level of consciousness of the patient in the post-traumatic vegetative state.
Example 3. and/b 228-11, 962-11, 1144-11, 421-12
Patient Hours, 24 years. Post-traumatic vegetative state, (the consequence of severe intracranial injury, brain contusion severe with the centers of the crush zone of the frontal and occipital lobes, diffuse axonal injury, removal of detritus frontal lobes).
The syndrome of the optic and oculomotor disorders. Pseudobulbar syndrome. Diencephalic syndrome. Tracheostomy. The gastrostomy tube.
By the beginning of observations in IMC RAS: vegetative state 6 months, 11 b. for LCS, the initial symptoms of spastic dystonia in the distal negamax medical treatment aimed at improving the consciousness of the patient has improved to 20-21 b. in LCS, but further positive dynamics were observed. After 2 months of increased spasticity-type multifocal dystonia (up to 4-3 6 mod. SHK. Ashworth), in other groups of muscle hypotonia. Weight 70 kg
Treatment according to the method prototype not applicable: localization of spasticity and the absence of contractures is not POS is olali to determine the most affected limb.
The first course of treatment (see Table. 3.)., put 500 IU of Xeomin (7,1 UNITS/kg of body weight). Three weeks of observation regressed spasticity (2-0 b. on mod. SHK. Ashworth) and abnormal postures. On LCS improvement to 29-30 b. (mobility +46., visual reactivity +0-16., auditory perception +26., alternative communication +3 b.). According to PAT: relative increase energy metabolism in the cerebellum and the brain stem by 13%. The duration of effect is 4 months.
After 5 months of spasticity by type secondary multifocal dystonia 3-2 b. on mods. Ashworth, LCS - 29-30 b. A second course of treatment (see Table. 3.), put 400 IU of Xeomin (5.7 IU/kg body weight). Two weeks of observation regressed spasticity (up 2-0 6. on mod. SHK. Ashworth), LCS improvement to 46-47 B. (mobility +5 b., visual reactivity +0-1 B., auditory perception +8 b., verbal communication +16., alternative communication +3 b.) with further positive dynamics.
After 6 months the increase spastic dystonia when attempting to walk (in the supine position increased not significantly) Spasticity - 4 - 2 b. on mod. SHK. Ashworth, LCS - 60 b. Held the third course of treatment (see Table 3), introduced 700 IU of Xeomin (10 IU/kg body weight).
After the third course in the three weeks of observation:
1. spasticity is reduced to 2-0 B. on mod. SHK. Ashworth.
Alucinado LCS to 73 points:
- mobility (+5 b.): was expanded to include voluntary movements of the limbs, including appeared fine motor skills, improved movement of head and eyes, language, swallowing, appeared facial expressions, eye reactivity (+1 b.): appeared blink reflex; -auditory perception (+2 b.): improved perception and recognition of objects, understanding complex sentence structure; -alternative communication (+3 B.);
-verbal communication (+2 b.): improved articulation, quality and meaning of verbal messages.
-improvement of cognitive activity, attention, expand the emotional range and appeared praxis.
3. PET: relative increase of the energy of glucose metabolism in the cortex of the left temporal and parietal-occipital region (13%).
In the future, for 7 months of observation, the positive dynamics of the psycho-neurological status continues, spasticity is not growing.
Treatment with the described method allowed to reduce multifocal spasticity and to restore the consciousness of the patient from the level of the vegetative state to a small consciousness, with further positive dynamics in the form of recovery of higher cortical functions.
Thus, as shown by the examples,the proposed method improves the quality and efficiency of treatment of the vegetative state: improves the treatment of generalized and multifocal spasticity, including its drug-resistant forms and simultaneously improves the level of consciousness and communicative activity of patients in a vegetative state and output stages. The method is effective, safe, easy to use, requires no special software.
A method of treating spasticity, accompanied by improvement of consciousness in patients in a vegetative state by repeated courses of botulinum toxin therapy using the drug botulinum toxin A, purified from complexing proteins (Xeomin), characterized in that for the duration of the course up to 3 weeks Xeomin injected into spastic muscles of all limbs and accompanying body segments regardless of contractures in a total dose of 400-1300 UNITS not exceeding 24 UNITS/kg of body weight, 1-3 phase, which is carried out with an interval of not less than 3 days; and at each stage lasting up to 1 day in every available muscle or muscle group with a maximum tone enter 5-50 UNITS in a total dose of not more than 500 UNITS, in the breeding of 12.5 IU/ml by the uniform distribution of the injection area muscles without electromyography; the following courses are conducted similarly to the case of increasing spasticity and/or clinical need.
SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.
EFFECT: compounds of formula I and II as histone deacetylase inhibitors.
18 cl, 18 dwg, 10 tbl, 19 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutics and represents a nutritional composition for an infant or: : a child containing lipid or fat, a protein source, a source of long-chain polysaturated fatty acids which contains docosahexaenoic acid; a supplementary calcium source to 2.5 wt % with at least 20% of the supplementary calcium source representing calcium gluconate, and PDGF-β 0.015 to 0.1 ppm (pg/mcg).
EFFECT: provided better digestibility as compared to the conventional compositions.
12 cl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biology, preferentially to medical genetics, and describes the agent for increasing life span of Drosophila melanogaster containing ammonium pyrrolidine dithiocarbamate (PDTC). The agent is orally administered in the concentration of 20 mg/l in the course of a lifetime. The agent is not gender-specific and enables increasing the life span of both male, and female Drosophila melanogaster considerably: average (improves quality of life) and maximum (delays the ageing rate).
EFFECT: increasing the life span.
2 cl, 1 tbl, 2 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: what is presented is using a composition containing galactooligosaccharide, fructooligosaccharide and uronic acid oligosaccharide in preparing a composition for oral administration into an infant for preventing the local administration of corticosteroids and/or preventing the administration of a calcineurin inhibitor into the above infant, wherein uronic acid oligosaccharide represents a pectin degradation product and/or an alginate degradation product, and wherein using the corticosteroids and/or administering the calcineurin inhibitor is applicable for treating eczema, infantile eczema, atopic dermatitis, dermatitis herpetiformis, contact dermatitis, seborrheic dermatitis, neurodermatitis, psoriasis and intertrigo. Particularly, the composition is a nutritional composition.
EFFECT: what is shown is reducing probability of the local administration of corticosteroids and dermatological preparations to be required for the purpose of preventing the above skin diseases, or reducing the length of using the corticosteroids.
5 cl, 2 ex
SUBSTANCE: invention relates to organic chemistry and specifically to novel 7-piperidinoalkyl-3,4-dihydroquinolone derivatives and a pharmaceutically acceptable salt or hydrate thereof, where R is a hydrogen atom or a C1-6-alkyl group; A1, A2 and A3, which can be identical or different, are each a hydrogen atom, a halogen atom; X is a C1-6-alkylene group; Y is a bond or a C1-6-alkylene group; Z is a bond or a C1-6-alkylene group, where the C1-6-alkylene group can be substituted with a phenyl group; W is a bond or an oxygen atom; and Cy is a phenyl group or a pyridyl group, where the phenyl or pyridyl group can have 1-3 substitutes which can be identical or different and are selected from a group consisting of a halogen atom, a cyano group, a C1-6-alkyl group, C1-6-alkoxy group, where the C1-6-alkyl group or C1-6-alkoxy group can be substituted with 1-3 halogen atoms, and a C2-6-alkanoyl group. The invention also relates to a pharmaceutical composition and a preventive or therapeutic drug based on the compound of formula (I) .
EFFECT: obtaining novel 7-piperidinoalkyl-3,4-dihydroquinolone derivatives, having antagonistic action on MCH receptor.
6 cl, 4 tbl, 10 ex
SUBSTANCE: invention refers to medicine, namely resuscitation and intensive care, and may be used in treating a craniocerebral injury. That is ensured by administering dexamethasone 0.3 ml and trental 0.4 ml into an inferior external orbital angle between an eyeball and a bone orbit, external and inferior rectus muscle of eye with underlying standard drug-induced therapy. The introduction is once a day daily for 5-7 days.
EFFECT: method provides the highest drug concentrations in the cerebral tissues once administered into the retrobulbar space over a shorter period of time than if administered otherwise that in turn leads to faster cerebral decongestion, peripapillar optic nerve decongestion, and as a consequence ensures faster coming out of coma of the patient with the craniocerebral injury.
SUBSTANCE: invention refers to medicine and may be used for preventing and treating the diseases wherein endogenous production of cytokines and hemopoietins is advisable to be stimulated. What is presented is a method for stimulating endogenous production of cytokines and hemopoietins which is based on introducing a preparation presenting a double-stranded genomic sonicated human DNA of fragment size 200-6000 base pairs into the patient's body. The preparation is used in the tableted form in the number of 3 tablets containing 5 mg of the active substance of the preparation daily for 1-14 days.
EFFECT: invention provides more effective stimulation.
1 cl, 21 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to medicine and described a complex prepared of a polysaccharide, particularly dextran, and a heparin-binding protein with the above polysaccharide being formed by (1,6) and/or (1,4) and/or (1,3) and/or (1,2) glycoside bonds and functionalised by at least one salt-forming or salt-transformed tryptophan derivative. The present invention also concerns a pharmaceutical composition containing the complex according to the invention.
EFFECT: using the complex ensures providing the better solubility and stability of the heparin-binding proteins.
10 cl, 12 ex, 2 tbl
SUBSTANCE: invention refers to medicine, and aims at treating acute radiation sickness. A therapeutic agent for a medullary form of acute radiation sickness is presented by light-isotope water.
EFFECT: using the declared invention enables higher survival rate, fastens hematopoiesis and body weight recovery.
3 tbl, 3 ex
SUBSTANCE: invention refers to agriculture, particularly to veterinary science, and may be used for the purpose of animal tissue radiosensibility enhancement. That is ensured by the pre-radiation parenteral administration of oxyglycine lithium salt in a dose of 40 to 120 mg per 1 kg of body weight.
EFFECT: invention provides the pronounced radio-sensitizing effect on the animal in experiment.
1 tbl, 1 ex
SUBSTANCE: composition for improvement of brain function as active ingredient includes peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (where X is absent or represents He or Asn-Ile; and Y is absent or represents Val-Met), peptide X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (where X is absent or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro; and Y is absent or represents Val-Met) or their salts. Method for improvement of brain function involves introduction of the above peptide or its salt.
EFFECT: invention allows effective prevention of amnesia and strengthening of memory at peroral use of a low dose of the above peptides.
35 cl, 6 dwg, 6 ex
SUBSTANCE: invention relates to a compound of formula or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition for treating β-amyloid diseases and synucleinopathies, based on said compound.
EFFECT: obtaining a novel compound and a pharmaceutical composition based thereon, which can be used in medicine to treat such diseases as Alzheimer's disease and Parkinson's disease.
17 cl, 38 dwg, 14 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine and pharmacology, and concerns a method of introducing a polypeptide containing an epidermal growth factor like (EGF-like) domain containing introducing the above peptide for at least two days after a neurological damage, as well as after a mammal reaches a full volume of the ischemic cell death following the damage.
EFFECT: invention provides treating the neurological damage in the post-acute or chronic period following the neurological damage to limit the cerebral damage, functional recovery and/or recovery enhancement following the neurological damage.
15 cl, 19 ex, 18 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, namely pharmacology and may be used for cerebral protection in treating cerebral affections. That is ensured by using Zongorine as a cerebroprotective agent.
EFFECT: agent provides the cerebroprotective action and prevents the death in animals suffering experimental post-hypoxic encephalopathy due to the activation of cerebral neutral stem cells.
2 ex, 3 tbl
SUBSTANCE: invention relates to novel (3-arylsulphonyl quinolin-8-yl-dialkyl-amines of general formula 1 and pharmaceutically acceptable salts thereof, which are selective antagonists of serotonin 5-HT6 receptors. The compounds can be used as an active ingredient in pharmaceutical compositions and medicinal agents for treating diseases of the central nervous system, pathogenesis of which is associated with 5-HT6 receptors. In particular, the compounds can be used in case of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Huntington's disease, in anxiety or cognitive disorders and for enhancing mental capabilities. In general formula 1 , Ar is phenyl, optionally substituted in position 3 with a halogen atom, or naphthyl, R1 and R2 are an unsubstituted methyl or ethyl.
EFFECT: improved method.
10 cl, 9 dwg, 2 tbl, 8 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical industry, particularly to an oral preparation, possessing antihypoxic, nootropic and hypolipidemic action. The oral preparation possessing antihypoxic, nootropic and hypolipidemic action contains a combination of vinpocetine and gingko extract in the relation of 1:(3.5 -16).
EFFECT: preparation possesses the pronounced antihypoxic, nootropic and hypolipidemic action.
2 cl, 6 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine and veterinary science. Compositions containing one or more unsaturated fatty acids and one or more compounds releasing nitrogen oxide, and methods for using such compositions for enhancing the cognitive function, reducing or preventing the deterioration of social interaction, reducing or preventing the age-related behavioural changes, increasing the learning capability, maintaining the optimal cerebral function, relieving the learning and memory processes, reducing loss of memory, providing the retardation of cerebral aging, preventing or treating cerebral accidents, and preventing or treating dementia in an animal.
EFFECT: group of inventions provides more effective enhancement of the cognitive function in mammals.
61 cl, 7 tbl, 2 ex
SUBSTANCE: group of inventions refers to medicine and aims at treating, preventing or relieving a disease or a condition which is to be treated, prevented or relieved by NMDA receptor inhibition. The method involves administering a total daily dose of approximately 2 to approximately 50 mg of a compound of formula
or a pharmaceutically acceptable salt thereof into the patient in need thereof. What is also declared is using the compound of formula (I) or a pharmaceutically acceptable salt thereof for treating, preventing or relieving the course of a cognitive disorders, a neurodegenerative disorder, pain, depression, attention deficient hyperactivity disorder or an addiction, and for treating, preventing or relieving the course of a disease or a disorder by inhibition of NMDA receptors containing an NR2B subunit wherein a total daily dose of the compound makes from approximately 2 to approximately 50 mg.
EFFECT: group of the inventions is high effective in treating, preventing or relieving the course of a disease or a disorder which is to be treated, prevented or relieved by NMDA receptor inhibition.
10 cl, 6 dwg, 3 ex
SUBSTANCE: versions of an antibody or its fragment, which are specific in relation to β-amyloid protein, are proposed. Each version is characterised by the fact that it includes H- and L-chains, or areas VH and VL, each of which contains three corresponding CDR. The following is described: polypeptide VL, polypeptide VH, as well as coding nucleic acid, expression vector containing it and a cell carrying the vector, which are used for obtaining an antibody or its functional fragment. The following is proposed; a test kit, versions of pharmaceutical composition, a mixture to be used as a medicine based on the antibody or its functional fragment. Versions of the method used for production of an antibody are described: using a cell, nucleic acid or a vector. A composite preparation method, as well as an in vitro amyloid disease diagnostics method, a method for determination of a degree of loading with in vitro amyloidogenic patches, a method for curing or relief of actions of amyloid disease, which use an antibody or its functional fragment, are described. Inventions can be used in therapy and diagnostics of Alzheimer disease and other enlisted amyloid diseases.
EFFECT: proposed inventions provide new antibodies that bind the epitope contained in the area of 12-23 protein αβ1-42; with that, residues 15-20 have a fundamental importance.
44 cl, 18 dwg, 9 tbl, 16 ex
SUBSTANCE: invention relates organic chemistry and specifically to novel pyridine amide derivatives of general formula I where n equals 1; R1 and R2 together denote a residue selected from a group consisting of -CH=N-NH- and -CH=CH-N=CH-, which is bonded in any desirable direction to the parent structure or R2 and R3 together denote a residue selected from a group consisting of -CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is bonded in any desirable direction to the parent structure, or R3 and R4 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, or R4 and R5 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, and the rest of the residues R1, R2, R3, R4 and R5, mutually independently, in each case denote H; where R28 denotes F; Cl; Br or I; R29 and R30, mutually independently, in each case denote -NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34; where R31, R32, R33 and R34, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R6 denotes H or denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R7 denotes hydrogen or -OH; R denotes -CF3; or denotes an unsubstituted tert-butyl residue; T denotes C-R35 and U denotes C-R36, V denotes N and W denotes C-R38; where R35 and R36 denote H; where R38 denotes -NR40R41; -OR42 or -SR43; where R40, R41, R42 and R43, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; or denote a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-member cycloaliphatic residue, or where R40 and R41 in each case together with a nitrogen atom as a ring member which binds them together, form a saturated 6-member heterocycloaliphatic residue, optionally substituted with one R57 residue, where R57 denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; in each case in form of corresponding physiologically acceptable salts. The invention also relates to a method of producing a compound of formula I, a medicinal agent based on the compound of formula I and use of the compound of formula I.
EFFECT: obtaining novel amide derivatives of pyridine, useful in treating vanilloid receptor 1 mediated diseases.
25 cl, 1 tbl, 18 ex
SUBSTANCE: invention refers to medicine, namely to physiology and space medicine. The method for prevention of skeletal muscle atrophy after functional unloading involves administering 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) which increases an amount of muscle heat shock proteins and further reduces a level µ-calpain.
EFFECT: invention enabling managing the negative effects of hypokinesia or gravity unloading through the enhanced inhibition key signalling pathways initiating atrophy.