A method of treatment of hyperkinesis in children

 

(57) Abstract:

The invention relates to medicine, in particular to pediatric neuropathology and can be used in the treatment of hyperkinesis in children. The method can reduce the side effects of drugs, to reduce the period of inpatient treatment and to prevent having a progressive process. For this exercise combined effect of pulsed current, and entered metoclopramide on the area of the fronto-orbital departments from device "LENAR" when the frequency of the pulse current 800 - 1000 Hz, amperage until the sensations of vibration under the electrodes, the duration of the treatment of 20 to 40 minutes treatment 10 - 15 procedures carried out daily. table 2.

The invention relates to medicine, namely to pediatric neurology, and can be used for the treatment of hyperkinesis in children.

Hyperkinesis is one of the most frequent signs of nervous system in children. This is due to ontogenetic peculiarities of the structure and function of the brain. A unified perspective on the etiology and pathogenesis of violent movements yet, which greatly hampers the rational therapy. Treatment of hyperkinesis includes the aqueous treatment. Widely used are the group of drugs benzodiazepines, however, due to multilateral action of these drugs is their use in pediatric practice is limited. In recent years in the treatment of hyperkinesis found use tools that reduce the activity of dopamine metabolism. These tools are most effective for this disease, but have significant side effects and toxicity, and that prevents their use in pediatric practice.

There is a method of treatment of TIC hyperkinesia by oral administration of haloperidol (see E. S. Bondarenko and others Experience long-term therapy with haloperidol and Orapa children with Tourette's syndrome.

The disadvantage of this method is the duration of drug intake to 4-5 years, the development of many children side effects such as extrapyramidal disorders, fatigue, reduced attention, and drowsiness. Some children developed side effect in the form of a significant increase appetite, which led to a significant weight gain of the child.

Of physiotherapy in the treatment of hyperkinesis in children was used bromine-electrophoresis by the method of A. E. Shcherbakov. However, the positive dynamics of clinical indicators expressed nedostatochnaia hyperkinesis (see A. S. Footer. Diseases of the nervous system in children. M.: Medicine, 1965).

The prototype of the present invention is the oral use of metoclopramide (erukala) with Tourette syndrome (see A. Y. Smirnov. About the use of metoclopramide (erukala) in Tourette syndrome. The journal Neuropathology and psychiatry. N 8, 1989, S. 105-108).

The disadvantage of this method is side effects as development of extrapyramidal disorders, allergic skin rash. If the dose described the development of malignant retinopathy. In addition, even in high doses, therapeutic effect is insufficient due to the low permeability of drugs through the blood-brain barrier after oral administration, therefore, require long-term use of the drugs in terms of monitoring of patients in hospital for the selection of an adequate dose.

The aim of the invention is to increase the effectiveness of treatment of hyperkinesis, reducing side effects of drug therapy, as well as shortening hospital treatment.

The proposed method for the treatment of hyperkinesis in children is the effect on the disease process in subcortical areas and limbic brain structures electrosleep-electrogasm. Use two pairs of bifurcated electrodes in the frontal-cervical location. The electrodes are moistened with a 5% solution of metoclopramide and alkaline buffer with hydrophilic strip with an area of 5 cm2disposed in the frontal region and linking them with the anode. The second divided electrode dipped in warm water, area of 10 cm2set on the mastoid processes. Used frequency pulse current 800-1000 Hz. The current intensity was adjusted individually until you feel a vibration under the electrodes. The duration of the procedure was 20-40 minutes the treatment is 10-15 procedures carried out daily. It was studied the effect of the drug metoclopramide on the locomotor activity of the brain.

In chronic experiments on rats were tested intracerebral injection of metoclopramide, and studied its effect on the conditioned reflex behavior and locomotor activity. The area of introduction - basal ganglia of the brain, the nucleus veins of the complex - elected due to their exceptional richness of dopamine receptors, which presumably affected the study drug, as well as the fact that these formations brain are involved in the pathogenesis of extrapyramidal diseases.

All animals before the start of the experiments were developed reflex active avoidance in the Shuttle chamber. Daily in 20 min after injection started conditioned reflex testing (estimated accuracy of reflex, the latent period and the number of passive isbahani) and determined the level of spontaneous locomotor activity (number of border crossings conditional squares, which divided the floor of the Shuttle camera). Behavioral testing was performed not only during microinjection, but within two to three weeks after their removal to register a possible aftereffect. According to histological/P> Observation of "false-operated" animals have shown that any variance in behaviour (compared with before surgery) were observed. In rats with physiological solution in the first 2-3 for the experiments were recorded irrelevant to the level of 60-70% accurate answers - reduction of the conditioned-reflex activity, but in the future, all behavioural measurements were within normal limits.

Microinjection of metoclopramide induced a decrease in the accuracy of the implementation of the reflex in the early stages of its chronic administration, in the first 4-5 days of experiments. Then rats gradually began to decrease spontaneous locomotor activity and, starting from the second week of experiments, it is almost completely absent. Moreover, hypokinetic effect of metoclopramide was observed within three weeks after discontinuation of microinjection. Externally, the behavior of rats was characterized by a General pacification, tranquilitatis, that did not prevent them correct conditional reflexes.

As an alternative product traditionally used for the treatment of hyperkinesis, was investigated neuroleptic haloperidol. Dose (5 μg), the method and mode of administration was identical series of experiments with the introduction of metoclopra is to rats was almost completely lost, movements were slowed, immobilized, was observed elements of rigidity of skeletal muscles. The rat was sitting in a hunched posture and negatively reacted to the touch and attempts to bring them out of this state. The observed phenomena were determined and after the microinjection.

The obtained experimental data show that metoclopramide unlike haloperidol causes a mild, but steady enough hypokinetic effect without violating the conditioned-reflex activity and motor dystonia. These data support the opinion about the involvement of the basal ganglia in therapeutic effects of metoclopramide and about the special, non-neuroleptic drug dopamine receptors, which can be used in pediatric neurology for the treatment of hyperkinesis. Information about the introduction of metoclopramide by electrophoresis in the available literature are not met. In this regard, the study of its formichetti.

Formichetti of the preparation was studied in model experiments using zonal electrophoresis media and instructional techniques (see Methods zonal electrophoresis. M.: Medicine, 1971). As a supportive environment using agarose Chemapd, Czechoslovak) - nose). Used wereanalogically buffer. pH 8,;6; 0.1 (veronal 2.76 g, Medina 17,52 g, distilled water to 1 l) with low electrical conductivity.

Study drug (50 ml ampoule officinal solution containing 10 mg in 2 ml) were introduced into the wells of the block of agarose 10 g/l and subjected to electrophoresis. For detection of the drug in the agrarian gel after electrophoresis was carried out color reaction on the amino group of metoclopramide

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Previously it was found that this reaction can be detected metoclopramide located both in solution and in agarose gel. After electrophoresis agrarian block was placed for 10 min in a solution of NaNO2(0.1 mol/l), acidified with 10 drops of 5 N. HCl. Then the solution was decanted, the unit was rinsed with distilled water and placed in an alkaline solution-naphthol (20 g/l) until the pink color in the concentration of the drug. The gel was washed from excess-naphthol and dried. When electrophoresis under pre-selected conditions (size of the block of agarose to 100 x 100 x 4 mm, current strength 8 MA buffer solution pH of 8.6, 0,1) metoclopramide migrated to the cathode.

Thus, it was first established that formichetti drug metoclopramide (zeruda and identifying its formichetti, allowed us to propose an original method of treatment of hyperkinesis.

Metoclopramide electrosleep electrophoresis apparatus "LINER" was held in fronto-cervical technique. In order to directly affect the area of projection of the frontal-orbital departments limbic structures of the frontal electrodes were attached to the anode and moistened with 5% solution of metoclopramide. The conducted research revealed formichetti metoclopramide proved the possibility of its introduction with the anode. Frequency 800-1000 Hz was chosen due to the fact that at this frequency is entered the largest number of medicinal substances. Current selected individually for each patient prior to the occurrence of vibration under the electrodes. The duration of the procedure 20-40 minutes required for the injection of therapeutic doses of medicinal substances. The course of treatment is 10-15 procedures carried out daily, provided enough lasting clinical effect.

The study included 32 children with TIC hyperkinesias in age from 3 to 14 years, 20 boys and 12 girls. Development of hyperkinesia was preceded by angina and acute respiratory infections in 6 children, Psychotrauma - 4 patients, surgical intervention - 2, closed brain injury in ariadny obstetric history, 5 patients - family history of ticks. Disease duration ranged from 1 month to 8 years. Prevailed patients with generalized TIC hyperkinesis (22), children with local forms were 10.

All patients were examined clinically. For objectifying data, we used the following survey: ENMG, teplovizionnoi study, biochemical analysis (determination of catecholamines in urine daily). These surveys were conducted before and after treatment.

The severity of hyperkinesia were evaluated on their frequency per unit of time. Hereditary movements were recorded using an electromyograph with apparatus biofeedback. The electrodes are superimposed on the muscles primarily involved in the hyperkinesis. The survey was carried out in the same conditions, at the same time of day (10 and 19 h) at rest and after emotional stress. Was allocated to 3 groups of patients:

0 - violent movements are absent;

1 - the number of violent movements less than 30 in 2 min;

2 - the number of violent movements 30-60 2 min;

3 - more than 70 in 2 minutes

P R I m e R 1. Patient B., age 7, I. B. N 1475, was hospitalized in the clinic building complaints about violent movement in the form of a "sapacitabine head" therefore the girl could not go to school, to communicate with peers. The illness started 1 month ago when he first came violent movement. At the beginning of the disease they were less intense and was interpreted by the mother as a "bad habit", but in the future, the severity of hyperkinesis has sharply increased. Perinatal history burdened, hereditary predisposition to the disease is not detected.

In neurological status: emocinalno labile, critical, configured to treatment. Permanent TIC hyperkinesis of the muscles of the neck, corresponding to 3 degrees on the proposed scale, in the form of sharp milonopoulos sapacitabine head, disappears in sleep, enhanced by emotional stress. Identified microecology neurological symptomatica, high tendon and periosteal reflexes, positive symptom of Huasteca on both sides.

Additional methods of research have shown:

when ENMG: SLEEPeff- 47 m/s along the facial nerve, the extension - 46 m/s, AmaxM answer: 3800 UV and 4300 MV, duration M reply 19 m/s in both nerves.

On theprogramme face full face and in profile asymmetry thermal background, mosaic areas of the face.

When IP is in ( - 21 mcg/day, While 7.3 µg/day).

The patient was started on treatment by the proposed method: applying effects metoclopramide electrosleep-electrophoresis on a projection area of fronto-orbital departments limbic structures, the frequency of the pulse current 800-1000 Hz, the duration of the procedure 20-40 minutes, the course of treatment is 10-15 procedures carried out daily. After 8 treatments there was a significant decrease hyperkinesia, but when you try to finish the treatment, they began to reappear when the provocations and the treatment was extended to 15 procedures then forced movements were stopped completely (0 - proposed scale).

Clinical improvement was confirmed and data of additional methods of research: SLEEPeff44 and 45 m/s; AmaxM answer 3200 UV and 4200 MV; duration M reply 17 m/s and 18 m/s: when imaging study of person - heat symmetric background. The content of catecholamines in daily urine corresponds to the age norm: 22.4 µg/day And 6.0 mg/day.

When you examine the patient after 2 months: hyperkinesia no, the girl goes to school.

P R I m m e R 2. Patient W., age 8, I. B. N 1215 was hospitalized in the clinic of nervous diseases of Lemigova with 5.02 on 23.02.9 that engage different muscle groups (shoulder shrug, blinking, preceptive"). Hyperkinesis accompanied by vocalizations, have behavioral disorders. Ill for 2 years, the disease first appeared in the background of SARS. Perinatal history burdened, in 6 years the transfer of a concussion.

The disease began with the emergence of violent blink movements that grew in frequency, and then to the existing movements were joined by new, engaging in hyperkinesis different muscle groups. The intensity sharply increased in frequency when excited and during voluntary movements, hyperkinesia disappeared during sleep. A year later he joined vokalizatsii. The boy ceased to attend school, could not travel in public transport, to read. Treatment carried out earlier, the effect is not reached. The boy's father in childhood took place TIC hyperkinesis.

In neurological status expressed polymorphic hyperkinesia, corresponding to 3 degrees on the proposed scale, the emotional background is reduced, disinhibited behavior, not disconnected, hypermature. Reflex right gamecentral.

Additional methods of research showed: ENMG SLEEPeff: along the facial nerve 44 m/s, the extension - 48 m/s; AmaxM answer: the facial nerve 3100 Teplovizionnoi study person - the FAS and the profile was determined by the asymmetry of thermal background. For biochemical analysis of urine on a daily concentration of catecholamines were determined: 22.4 µg/day; And 8,0 mg/day.

During the first procedures metoclopramide-electro-electrophoresis using the proposed methodology, procedure duration was 50 minutes, but it did not increase therapeutic effect and it is difficult transferred to the sick and the time was shortened to 30 minutes At the beginning of treatment showed negativity for the procedures. After holding 15 procedures the severity of hyperkinesis decreased significantly and became correspond to 1 degree on the proposed scale. The observed improvement in neurological symptoms was confirmed and data of additional methods of research: ENMG SLEEPeff: along the facial nerve 40 m/s, the extension - 45 m/s: AmaxM resp. 3100 MV: extension 3900 MV; duration M answer: the facial nerve 16 m/s, the extension - 17 m/C. When thermal study of thermal background was symmetric, the content of catecholamines in daily urine: A 5,0 µg/day; 8.0 mcg/day.

Examination of the child after 2 months showed that the hyperkinesia are revealed only by provocations, normalized povides 5.03 on 26.03.91, Diagnosis: local TIC hyperkinesis.

Was admitted with complaints of enforced motion in the form of frequent blinking (blepharospasm). Ill 2 years, the disease limitiruyuschie. Obstetric history burdened, frequent sore throats. Conducted differentially diagnosed with a rheumatic affection of the Central nervous system. Previously held courses of treatment according to traditional methods improvement was brought. Neurologically: detected broken microecology symptoms, impaired emotional tone, tearfulness, effective explosiveness. If additional examination methods were observed: ENMG SLEEPeff: along the facial nerve 45 m/s, the extension - 47 m/s; ANDmaxM response 3600 MV, as additional nerve 4000 MV. The length M of the response along the facial nerve 18 m/s, the extension - 19 m/s In the study of thermal background of the person revealed mosaicism heat figure, when biochemical analysis of urine on the content of catecholamines (adrenaline and noradrenaline): 10.3 µg/day; While 7.3 µg/day.

During the course of treatment proposed method was taken as the frequency of the pulse current of 700 Hz, after 15 treatments, the severity of clinical effect was negligible, reducing the severity of gipe was repeated at a frequency pulse current 900 Hz, clinical effect was observed already after 5 treatments. The girl received 10 sessions metoclopramide-LUNAR electrophoresis. Hyperkinesis full - Tue disappeared.

ENMG SLEEPeff: along the facial nerve 43 m/s, the extension - 45 m/s: AmaxM answer 3500 UV and 3800 MV; duration M reply 17) and (18 m/s were Observed improvement. Thermal study of the person, thermal background is symmetric, the content of catecholamines in the urine returned to normal and was 12 μg/day; And of 4.9 µg/day.

Examination after 3 months: hyperkinesia not defined, the emotional tone of a stable, normalized behavior.

P R I m e R 4. Patient P., aged 14, I. B. N 1468, was treated at the clinic of nervous diseases of Lemigova with 10.03 on 26.03.91, Diagnosis: generalized TIC hyperkinesis on residual organic background.

Ill for 8 years. The disease appeared after traumatic brain injury. When entering noted a pronounced TIC hyperkinesis facial muscles, muscles, necks, limbs. Did not attend school for 1 year.

Neurologically: right reflex gamecentral, vegetative disturbance in the form of vegetative-vascular dystonia on hypertonic type, obesity.

During the course of treatment metoclopramide LUNAR electrophoresis was taken frequency pulse current of 1100 Hz. When conducting the 3rd procedure, our son had burns on the forehead. Therefore, the frequency was reduced to 800 Hz, and then a course of treatment consisting of 10 treatments (after 12 days break). After the end of treatment was observed clinical improvement, hyperkinesia decreased and began to meet the 2 degrees on the proposed scale.

Laboratory studies showed a slight positive trend in the reduction of conduction of the impulse along the facial nerve, SLEEPeff40 and 48 m/s; ANDmaxM answer 3200 and 4600 MV; duration M reply 16 and 18 m/s

Decreased intensity of infrared radiation to the right. The content of catecholamines in urine daily: 19 mcg/day; 5 mg/day.

Examination after 3 months his condition stabilised the data of different parameters impact the most rational was holding metoclopramide-electrosleep electrophoresis at frequency pulse current 800-1000 Hz, amperage, individually selected according to the occurrence of small drain vibration under electrode, the duration of the procedure 20-40 minutes and a course of treatment consisting of 10-15 procedures that were used in other cases.

As a result of the treatment metoclopramide-electro-electrophoresis using the apparatus of LINER in patients with TIC hyperkinesia positive clinical effect was achieved in 27 of the 32 patients (84.3 percent), mainly with generalized forms, low severity organic changes in the nervous system and disease duration up to 2 years. 5 patients experienced less clear positive trend in the form of ischemia ticks up to 2 degrees, which was assessed as insufficient clinical effect. Side or adverse reactions were observed. A number of children after the first procedures noted some weakness, which later disappeared.

Analyzing the dynamics of paraclinical indices presented in table. 1, we can conclude that in children with hyperkinesis there was an increase in SLEEPeffon the front and incremental nerves (in comparison with the control group), there has been an increase in the amplitude and duration of the M response, thus, ENMG bolnichnii duration M response. After treatment, the decrease of the values ENMG probably by reducing the activity of dopaminergic systems. Thus, the initial level of performance ENMG when hyperkinetic syndromes can serve as a criterion of patients for treatment with metoclopramide.

By analyzing data from imaging studies, we can say that observed when hyperkinesia the asymmetry of thermal background or mosaicism may indicate violation of the autonomic cardiovascular regulation in this group of patients. Normalization of these parameters occurs simultaneously with clinical improvement, which may indicate improved vegetative-vascular regulation and be an additional criterion to determine the duration of treatment.

When urine daily concentration of catecholamines revealed increasing amounts of adrenaline and noradrenaline in urine daily, which confirms the voltage of the sympathoadrenal system in this group of patients. Normalization of these parameters after the treatment indicates reduced activity of catecholamine metabolism, which is also the criterion of length of treatment and number of courses.

When studied by the light of the elimination or significant reduction in the severity of hyperkinesia and normalizes the psycho-emotional state, without causing the side effects of drugs, which usually occurs when drug therapy.

After finishing the procedures, the majority of patients noted a decrease in the emotional irritability, mild drowsiness, decrease hyperkinesia. After conducting 10-15 procedures revealed the complete disappearance or significant reduction in the severity of hyperkinesis. The positive clinical effect identified in 84,3% of cases, the treatment in the traditional way - in 58%.

Thus, we can conclude that this method of treatment aimed at normalizing the activity of the catecholamine system and the regulation of vegetative-vascular innervation is effective and can be applied in the treatment of TIC hyperkinesia in child neurology.

Positive dynamics in the clinical picture was revealed in 84,3% of patients. The control group consisted of 30 patients who received treatment on the prototype. Comparison of results of treatment offered and known methods are presented in table. 2.

The proposed method for the treatment of hyperkinesis has a number of advantages compared with the known:

no side effects of drug therapy along erodov, able to protect the child's body from the abundance of medicines;

the method is simple, painless and well tolerated;

therapeutic effectiveness of the proposed method of treatment allows to reduce terms of patients ' stay in hospital, it can also be used in polyclinic conditions that will avoid hospitalization, which is traumatic effect on the child.

Thus, the proposed method for the treatment of hyperkinesis in children has a pronounced therapeutic effect, which is confirmed by the positive dynamics in the clinical picture of the disease and the dynamics of paraclinical studies. The novelty of the method is the combined effect of pulse current and put them metoclopramide impact on the area of projection of the frontal-orbital departments limbic structures. The method can be used in complex treatment of patients both inpatient and outpatient conditions.

A METHOD of TREATMENT of HYPERKINESIS IN CHILDREN, including the introduction of metoclopramide, wherein the drug is administered by electrophoresis with simultaneous introduction of the patient in electrosleep exposed to the pulsed electric current frequency of 800, the course of treatment 10 - 15 procedures.

 

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