RU2506968C2 - Method of treating vegetative state - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to neurosurgery, resuscitation and neurology, and may be used for treating the permanent unconscious vegetative state. That is ensured by intratympanic streptomycin treatment with underlying common drug therapy of the state. The completion of the above is followed by the electric transcranial exposure on the brain. For the intratympanic treatment, streptomycin 1 g is dissolved in physiologic saline 1 ml. The preparation is introduced once a day from one side, and on the other day from the opposite side. The therapeutic course is 5-10 days. The electric transcranial exposure is presented by transcranial DC micropolarisation of intensity 200-400 mcA for 30-40 minutes daily for 16-24 days. The exposure is performed through 3-4 electrodes places on the areas of temporo-caudal projections and posterior associated cortical areas from both sides. For the first 6 days, such exposure covers the temporo-caudal projections, while on the other days the posterior associated cortical area projections are exposed. If required, the above therapeutic courses are repeated not earlier than in 3 months until the clear consciousness is reached.

EFFECT: method provides an immediate and convincing clinical effect without brain invasiveness, an ability to recover the clear consciousness in these patients, as well as a significant reduction of the pathologically increased muscle tone and as a result, achieved satisfactory level of the patient's self-service.

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Description

The invention relates to medicine, namely to neurosurgery, resuscitation and neurology, and can find application in the treatment of prolonged unconsciousness.

By a vegetative state (VS) is meant a state in which, after leaving a coma, any cognitive ability is lost, despite the relative preservation of the waking state and the stability of vital functions, such as breathing and cardiovascular activity. Such patients do not recognize the environment and do not respond to speech addressed to them.

Up to 25 thousand adults and up to 10 thousand children live with AF syndrome in the USA [Fields A.I., Coble D.H., Pollack M.M. at al. Outcomes of children in a persistent vegetative state / Crit. Care Med - 1993 - Vol.21, No.12 - 1890-1894]. For Russia, such statistics are not available.

The financial, personal and technological resources spent on the maintenance and treatment of vegetative patients are disastrously large. In the first year in a hospital, the money spent reaches $ 129,000 ± $ 51,000 for each patient. In subsequent years, the price of maintenance is reduced to $ 32,000 ± 3%.

The outcomes of the disease in patients observed at home are very unfavorable: in the best case, they expect a minimal manifestation of consciousness, and 30% of patients die within the first year after discharge from the hospital. This is the reason why in some countries specialized centers for the medical care of this difficult group of patients are being created. In Russia, such patients are in most cases at home under the care of close relatives.

It should be noted that in connection with the further development of resuscitation, the number of patients in the Armed Forces is steadily increasing. Thus, according to the available data, only 2000 new cases of AF are reported annually due to trauma [Principles of Neurosurgery / by Ed. R.G. Grossman, CM. Loftus - Lippincott - Raven, Philadelphia - New York - 1998 - P 117.].

Drug treatment of the sun, in which in addition to the lack of cognitive activity there are gross violations of tone, implies symptomatic therapy. To correct muscle tone, drugs such as baclofen and L-Dopa are used. In order to activate metabolic processes in the brain, nootropics are used (piracetam, nootropil, cortexin). Drugs are also used whose action is aimed at improving cerebral blood flow (Actovegin, Instenon, Trental, Cavinton). Recently, the precursor of acetylcholine, gliatilin, has been widely used to treat these patients. Together with drug therapy, methods of multisensory stimulation (visual, auditory, etc.) and various physiotherapeutic methods are used. The lack of effectiveness of this therapy is the reason for the search for new, more effective high-tech methods of treatment of this pathology. There is a method of treating AF by implanting embryonic cells in atrophic parts of the brain [Tsymbalyuk V.I., Martynyuk V.Yu., Volkova T.G., Pichkur L.D., Gordienko O.V., Scherba I.N., Suliy N .N. A method for the treatment of apallic syndrome / Patent for the invention No. 2028089 - 09/09/1995]. This method has been applied in children. When using it, there was a transition to wakefulness under the influence of auditory stimuli, there were reactions of revival to the mother's voice. Then came tracking, a smile, laughter, pronunciation of individual syllables. Children began to recognize their mother, elementary neatness skills, elements of game contact, etc. arose. This method of treatment was used only in children, and long-term results were not studied. In adult patients with VS, the results of using this treatment method are not known.

Various types of electrical effects on the brain are known. These methods of exposure include: transcranial electrical stimulation, electrical stimulation of the deep parts of the brain, transcranial electrical stimulation of the brain stem. The achieved results are not unambiguous, not presentable and leave much to be desired, which is confirmed by the single nature of these works and the absence of at least a satisfactory solution to this problem as a whole.

Closest to the proposed method is transcranial frequency electrical stimulation (TES) of the brain in patients with AF, which we took as a prototype (E.V. Sharova, V.G. Amcheslavsky, A.A. Potapov, V.L. Anzimirov, O . S. Zaitsev, V. K. Emelyanov, V. A. Shabalov. EEG effects of therapeutic electrical stimulation of the human brain in the post-traumatic unconscious state. Human Physiology, 2001, Volume 27, No. 2, pp. 29-31). In this case, the electrodes are applied to the skin of the frontal (negative pole) and mastoid (positive pole) areas, followed by the therapeutic effect of an electrical nature on intracranial structures with rectangular DC pulses with a frequency of 30 Hz and a force of 3 to 5 mA. The duration of a TPP session is 30 minutes, the course dose is from 10 to 20 sessions. When applying this method, it was possible to extend the wakefulness of patients, sometimes to achieve a state of small consciousness in them. In this case, the pathologically increased tone did not change, and, in general, this work was devoted to the assessment of electroencephalographic changes against the background of a brain TPP. The authors themselves in the article do not mention the undesirable consequences of this effect. However, in our opinion, the disadvantages of the prototype are:

1 - frequency stimulation of the brain requires large values of the applied current (3-5 mA), which often leads to undesirable local phenomena, which include electric burns.

2 - frequency stimulation of the brain threatens the development of epileptic seizures

3 - frequency stimulation does not have a positive effect on trophic processes in the brain.

4 - The main scope of TPP is limited to pain syndromes of various origin and the contraindication to its use is the presence of epileptic seizures.

5 - TPP has little effect on pathologically altered muscle tone.

The technical result of the present invention consists in the possibility of recovery in patients with BC of clear consciousness, as well as a significant reduction in pathologically increased muscle tone, which allows to provide a level of satisfactory self-care.

This result is achieved by the fact that in the known method of treating AF by electrical transcranial action on the brain against the background of conventional drug therapy according to the invention, intratympanic administration of 1 g of streptomycin diluted in 1 ml of physiological solution 1 time per day is carried out once and on the other day on the opposite side for 5-10 days, and transcranial micropolarization with direct current of 200-400 μA 30-40 minutes daily for 16-24 days through 3-4 electrodes that are applied to the zones of the temporo-caudal projections and posterior associative cortical zones on both sides, the first 6 days having such an effect on the zones of temporal-caudal projections, and on other days, on the projection of the posterior associative cortical zones, if necessary, repeat such courses of treatment no earlier than 3 months before reaching a state of clear consciousness.

Transcranial micropolarization (TCMP) is widely used in neurological practice for the treatment of various manifestations of neurological deficiency, as well as for the treatment of epileptic manifestations in children.

While working in the emergency hospital, we dealt with the problems of severe traumatic brain injury and the TCMP method was widely used for its treatment. When using TCMP in VS, we noted an increase in the periods of wakefulness, but there was no effect on the pathologically increased muscle tone. Meanwhile, a decrease in muscle tone in this category of patients is one of the most important tasks of their rehabilitation.

Previously, we used the transtimpanal chemical vestibular dereception (TTHVD) method for extrapyramidal pathology, and its use led to a significant decrease in pathological muscle tone.

(Methodical recommendations “Transtimpal chemical vestibular dereception in the complex therapy of post-tonic disorders in diseases of the brain”, St. Petersburg Research Institute named after V. Bekhterev, 2011).

We decided to try to apply this method in the sun. At the same time, its use was contrary to existing ideas about the treatment of such patients, since, on the contrary, multisensory stimulation is necessarily used for their treatment. Nevertheless, taking into account the hopelessness of this category of patients and the futility of the therapy, we nevertheless tried with caution to use TTHVD in one patient. To our surprise, after two injections of streptomycin into the middle ear cavity, alternately on the left and then on the right, in addition to a decrease in muscle tone, we noted the appearance of signs of consciousness. This was the reason for the continuation of such treatment, and after 6 procedures, the patient with BC reached the level of akinetic mutism. This fact was the reason for carrying out such treatment to another patient, and he had the same effect. The achieved results, despite their positivity, did not quite suit us, since the patients were still not accessible to the contact. In this regard, we decided to add TCMP to the treatment.

According to the generally accepted technique, anodes are superimposed in temporocaudal projections, while the cathode is superimposed on the vertex (3 electrodes). When using such a scheme in patients with VS, we noted the appearance of signs of elementary contact in the first patient. This fact was the reason for the application of this scheme of exposure in subsequent patients with sun. When a patient with a traumatic brain injury arrived at the clinic, having a lesion in the right posterior associative zone, we tried to lay an anode over the zone of this lesion, as well as in a symmetrical region on the opposite side. The positive result obtained with regard to consciousness significantly exceeded the effects of impacts on the zones of the temporal-caudal projections. This fact allowed us to further use a combination of both schemes of action on the brain of patients with AF. Moreover, the sequence of effects, their sequence and number were determined by us in the treatment of the first 10 patients. So the scheme of the proposed method of treatment was worked out.

The non-obviousness of the result is confirmed by the fact that during our report on the first results we received at the Polenovsky readings in St. Petersburg, one of the country's leading specialists dealing with the problem of treating AF suggested that our method runs counter to conventional treatment methods.

Nevertheless, continuing to use the proposed treatment regimen, we invariably received the same unexpected results for us.

In all treated patients, along with a significant decrease in muscle tone, we noted a restoration of consciousness within 5-7 days from the start of treatment. Patients began to fix their gaze, monitor their surroundings, respond to relatives and medical personnel, and stay awake for longer. They began to appear spontaneous movements, targeted reactions to pain irritations. Gradually, swallowing function was restored. There were attempts at speech activity. At the end of the course of treatment (after 3 weeks), the achieved result made it possible to transport patients in a wheelchair to the department. Patients from the intensive care unit could be transferred to general wards provided that they were individually cared for by relatives. After 4-6 weeks, patients were discharged home under the supervision of the district service and relatives.

The invention is illustrated by the following examples.

Example No. 1. Patient St. 1954, year of birth, and.b. No. 2017. was treated in the Department of Surgery for Nervous and Mental Illness NIPNI them. V.M. Ankylosing spondylitis from 09.09.10 to 11.11.10.

From the anamnesis it is known that as a result of an accident on 02.16.10, she received a combination of severe brain injury with a severe brain contusion with compression of the left-sided subdural hematoma and a comminuted fracture of the left tibia. 02/17/10 was performed decompressive trepanation of the skull in the left frontotoparietal-temporal region, removal of acute subdural hematoma, right-sided diagnostic trephination. Subsequently, a tracheostomy, gastrostomy, epicystostomy, and Ilizarov apparatus on the left shin were performed. She went through several courses of inpatient treatment at the Vsevolozhsk Central District Hospital, the Institute of Neurosurgery Polenova.

Upon admission to the clinic 9.09.10 consciousness at the level of alternating sleep and wakefulness. Rare attempts to fix the gaze, there are no spontaneous movements, the command does not execute. Pupils D = S, DFG saved. The movements of the eyeballs are tentatively unlimited. Hypomimia. Trismus chewing muscles. The tongue behind the line of teeth, swallowing is disturbed in phases 1 and 2. Pain is not localized. In the extremities - decortication stiffness with the formation of muscular-articular contractures of all joints, Tendon and periosteal reflexes from the arms and legs D = S low, tetraparesis, more pronounced in the left extremities. Spasticity in limbs up to 5-4 points according to Ashworth. Diffuse muscle atrophy. Cachexia. Physiological administration is not controlled. Receives probe nutrition.

Locally: tracheostomy, gastrostomy, epicystostomy, bedsore of the sacral region, 7-8 cm in size. In the places of standing of the spokes of the Ilizarov apparatus - expressed granulation.

The treatment was performed: 09/16/10, cranioplasty was performed with a titanium mesh in the left fronto-parietal-temporal region, the course of TTXVD from 2 sides No. 8 was alternately in the left, and the next day in the right ear. There was a significant decrease in muscular tone from two sides, it began to fix the gaze, follow the environment, recognize relatives, there were elementary emotional reactions. However, there was a single vomiting and hypotension appeared up to 80/50 mm Hg. The course of treatment by TTHVD decided to end. The course of TCMP started. In the first 6 days, the anodes were superimposed on temporocaudal projections from two sides, and the cathode was placed on the vertex. The exposure duration was 40 minutes. A further increase in the level of consciousness was noted, hemodynamics stabilized at 100/60 mm Hg, the patient landed in a chair, holds objects in his hands, swallowed independently - he could swallow several tablespoons of crushed food, choked with liquid food. The next 18 days, the anodes were placed on the projection of the posterior associative zones of the brain - anodes on both sides, and the cathodes, in the amount of two pieces as well, on the frontal areas of the head on both sides. At the same time, further positive dynamics was noted, began to perform simple tasks, there were attempts at speech. After the 18th TCMP in the area of associative zones, the patient developed a generalized convulsive seizure in the evening. It was decided to complete the TCMP course. The indicated treatment was carried out against the background of standard drug therapy. Vitamin therapy was carried out, nootropics in large doses, received L-dopa preparations, metabolic therapy (cytoflavin, riboxin).

Upon discharge, partially regained consciousness. There are simple emotional reactions caused by situationally conscious fixation of the gaze. Eating by mouth up to 400.0 ml per day. Performs simple commands. There is spontaneous motor activity, but at a low level. There are elements of mutism. Regressed trismus of masticatory muscles. Spasticity in the limbs decreased to 1-2 points on the Ashworth scale. Dosed verticalization is carried out (to a sitting position within 1 hour). During the stay, with the gradual regression of pathological neurological symptoms, the tracheostomy tube, gastrostomy and epicystostomy were removed. The Ilizarov apparatus was removed due to the lack of adequate fixation of bone fragments and due to chronic inflammation in the knitting needles. The drumstick is fixed with a plaster cast. When discharging ¼ food by mouth, the rest through a naso-gastric tube. Discharged under the supervision of relatives and the local community service in the state of moderate severity.

Re-hospitalization

Patient St., born in 1954. I.b. No. 692/2011. Was on treatment from 03/10/11 to 04/06/11.

Anamnesis is known. Upon receipt of 10.03.11. - consciousness closer to clear, somewhat impoverished. Cerebration. Full communication. There is colloquial speech. During a conversation, mild dysphonia is determined due to the formed tracheostomy fistula. Eats independently from a spoon. He writes. Draws. Light tetraparesis, more pronounced in the left limbs and in the distal parts. The addition of muscle mass and weight. Physiological administration is partially controlled. Moves in a wheelchair with outside help. A full-fledged activation of the motor regimen is impossible due to an unconsolidated fracture of the left tibia.

The treatment was carried out: 03/29/11 operation - excision of the tracheostomy fistula, plastic tracheal defect. The course of TTKHVD from 2 sides No. 8, the course of TCMP No. 16 is similar to the first course of treatment. Considering that after the 18th TCMP session, the patient developed a generalized convulsive seizure during the previous hospitalization in the region of the posterior associative areas of the brain, the number of effects on these areas was reduced to 14. A course of drug-conservative vascular, cerebroprotective, metabolic, nootropic therapy was carried out. At discharge, there is further positive dynamics in the form of a further regression of an increase in the level of consciousness, a decrease in the severity of cerebastenia, speech disorders, an increase in the degree of motor activity. It is discharged under the supervision of a neurologist at the place of residence in a satisfactory condition.

Recommended: Repeated hospitalization after 0.5 years as agreed, with a view to further rehabilitation after stabilizing surgery on the left leg. Speech therapy classes. Gradual activation of the motor mode.

Example No. 2. Patient D-co born in 1997, and.b. N 502/2011, was in the Department of Surgery for Nervous and Mental Illness from 02/21/2011 to 03/11/2011.

From the anamnesis it is known that in June - July 2009, the patient suffered a meningo-encephalitic form of tick-borne encephalitis. The course of the disease is severe. Coma - 5 weeks. Mechanical ventilation, tracheostomy, cachexia, pressure sores, deep tetraparesis D <S. She was treated at the Institute of Children's Infections, and to restore spontaneous breathing she was transferred to the regional hospital, from where she was discharged home. Subsequently, she was repeatedly treated in hospitals with a neurological and rehabilitation profile with insignificant positive dynamics. Disabled person of group I.

On admission 02.21.2011 - the condition is compensated, breathing is adequate. Cachexia. Arterial hypotension. From the internal organs without pathology. Stool 1 time in 4 days after an enema. Urination independent in diapers.

Neurologically: there is no fixation of the gaze, it doesn’t respond to treatment, it doesn’t react to pain irritations, it is quickly exhausted, it is doubtful - it lies with eyes closed for a longer time and does not open them to treatment or pain. Food through a probe. Emotional reactions are absent. The position of the eyeballs is correct, the pupils are D = S, and the FRZ is live. The face is symmetrical. Trismus chewing muscles. The head is forcibly tilted to the right shoulder. Diffuse muscle atrophy against the background of spastic tetraparesis D <S. Equinus stop position. There are no articular contractures.

Medical treatment was carried out: vitamin therapy, magnesia therapy, antihypoxants, PK-Merz 50 mg iv twice a day - 10 days. Against the background of drug therapy, taking into account the highest severity of spasticity in the left extremities, a transtimpanic chemical vestibular dereception on the right was performed, the next day a significant decrease in muscle tone in the left extremities was noted. Activation of the patient was also noted in the form of an increase in periods of wakefulness. On this day, the TTHVD was made on the left. After the procedure, a decrease in pathological muscle tone in the right extremities was noted. The next day, a further increase in the level of wakefulness was found. Attempts have been made to fix the gaze on circulation. Subsequently, through laziness, alternately from one side, and the next day from the other side, another 2 TTKHVD on the right and 1 TTKHVD on the left were produced. After carrying out this treatment, the patient generally lies with her eyes open all day, steadily fixing her gaze for treatment. According to my grandmother, she smiles at her, watches TV. The violent tilt of the head disappeared, the trismus of the masticatory muscles decreased. Now you can open your mouth. At the same time, signs of vestibulopathy are determined in the form of nystagmus at the extreme position of the eyes, 1-2-fold vomiting during the day, attacks of sweating. In connection with the development of vestibulopathy, the course of TTHVD is completed. The course of transcranial micropolarization has begun. In the first 6 days, the anodes were located above the temporocaudal projection area on both sides, and the cathode was mounted on the vertex. The duration of TCMP, taking into account the age of the patient and the thickness of the skull bones, was 30 minutes. After 6 daily procedures, a regression of the manifestations of vestibulopathy was noted. At the same time, there is a further increase in the level of consciousness and the appearance of signs of sustained attention in the form of a long fixation of the gaze to the circulation, tracking movements of the eyeballs, viewing the presented toys, watching children's television shows. There were more pronounced emotional reactions to relatives and medical staff. Subsequently, when conducting TCMP, 2 anodes were located in the projections of the posterior associative zones on both sides, and 2 cathodes in the frontal areas. After 12 electrical actions according to the indicated scheme, a further increase in the level of emotionality was noted, spontaneous movements in the extremities appeared, he can swallow finely mashed food on his own, although he continues to receive main nutrition through a probe. Given the likelihood of developing epileptic seizures with continued TCMP and taking into account the patient’s childhood, the course of TCMP is completed.

As a result of the treatment, activation of the patient is noted, drowsiness, exhaustion decreased, more time is in an awake state. Contact with relatives expanded, sometimes performing simple tasks, became more emotional, steady attention appeared, interest in the environment. Spasticity in the limbs significantly decreased from 3 to 1 point on the Ashworth scale. The violent tilt of the head has disappeared. The trismus of chewing muscles was significantly reduced. She was discharged home under the supervision of relatives and the local medical service with a recommendation for a second course of treatment after 0.5 years.

Re-hospitalization

Patient D-ko, born in 1997, and.b. N 2169/2011 was treated from 09/21/2011 to 10/07/2011. Received for a second course of treatment.

Upon receipt of 21.09. 2011- conscious, the main time of the day lies with his eyes open. Watching TV. According to relatives, he reads the presented text. Examines pictures. Feeding through a tube, however, can swallow liquid and solid foods you like. She listens to music with pleasure (before the illness she showed good musical abilities). Emotional. Smiles to others. I recognized the attending physician. The position of the eyeballs is correct, the pupils are D = S, and the FRZ is live. He fixes his gaze for a long time, listens to speech addresses. Mimic paresis of the facial muscles on the right. Trismus of the chewing muscles is absent. The position of the head is correct. Diffuse muscle atrophy is much less pronounced compared with previous hospitalization. Moderate spastic tetraparesis D> S (to previous hospitalization D <S). There are high amplitude spontaneous movements of the left limbs, to a lesser extent - the right. The equinus position of the feet has decreased significantly.

The treatment was carried out: vitamin therapy, antihypoxants, PK-Merz 50 mg iv every other day 2 times a day - 10 days, nootropics. Given the predominance of muscle tone in the right extremities, 3 transtimpanal chemical vestibular deceptions on the left and 2 on the right were performed. At the end of the course of TTHVD, there was no vestibulopathy in this hospitalization. After the course of TTHVD, a course of transcranial micropolarization was carried out according to a scheme similar to the first hospitalization No. 18.

As a result of the treatment, further activation of the patient is noted. Contact with relatives and medical staff, as well as physical activity, has expanded. Actively performs non-complex tasks. He follows others, actively looking, watching TV for a long time. Spasticity in the right extremities has significantly decreased, the trism of chewing muscles has disappeared, and, upon request, opens his mouth. Further expansion of contact with others is noted. There was a game behavior, laughs out loud when they make her laugh. Verticalization started. He sits with the support of his grandmother. Discharged home under the supervision of relatives and the local service with the recommendation of a second course of treatment after 0.5 years.

Currently, the proposed method treated 29 patients with AF at the age of 13 to 65 years, of which 20 were men and 9 women. The majority of patients with AF had a traumatic etiology. Only 3 patients with BC developed due to tick-borne encephalitis, vascular catastrophe or due to hypoxia. All patients regained consciousness, self-service skills appeared, patients are available to almost full-fledged, including speech, contact and are sufficiently socialized.

The advantages of the proposed method are:

1. The method allows to achieve a quick and convincing clinical effect within 3-5 weeks, while similar results are not achieved with any of the known methods of treatment.

2. Allows treatment without invasive effects on the brain.

3. The method does not require special high-tech equipment.

The method was developed in the federal budgetary state institution "Research neuropsychiatric institute. V.M. Ankylosing spondylitis ”of the Ministry of Health and Social Development of the Russian Federation and was tested on 29 patients with positive results.

Claims (1)

A method of treating a vegetative state by electrical transcranial action on the brain against the background of conventional drug therapy, characterized in that it is preliminarily administered intratympanically with 1 g of streptomycin diluted in 1 ml of physiological saline, 1 time per day from one side and the other day from the opposite side for 5-10 days, and transcranial micropolarization with direct current of 200-400 μA for 30-40 minutes daily is used as an electric transcranial effect and over 16-24 days through 3-4 electrodes that are applied to the zones of the temporo-caudal projections and posterior associative cortical zones on both sides, the first 6 days having such an effect on the zones of the temporal-caudal projections and on the remaining days on the rear projections associative cortical zones, if necessary, repeat such courses of treatment no earlier than 3 months before reaching a state of clear consciousness.