The method of treatment of patients with persistent vegetative state

 

The invention relates to medicine, namely to neuroregenerative, neurosurgery and neurology. Record the electroencephalogram (EEG). When identifying hypersynchronization EEG conduct clinical anaesthesia for opioid analgesics and2-adrenoagonists until stable monotonous flat EEG and termination of stem activity, followed by a multimodal stimulation. When identifying the source monotonous flat EEG conduct a multimodal stimulation on the background of the introduction of the benzodiazepines. While benzodiazepines administered in doses not exceeding therapeutic effect of midazolam in a dose of 0.15 mg/kg Method can improve the effectiveness of the treatment. 4 C.p. f-crystals, 8 ill.

The invention relates to medicine, namely to neuroregenerative, neurosurgery and neurology, and can be used for the treatment of patients with persistent vegetative state (PVS).

There is a method of treatment of patients with PVS non-traumatic Genesis (post-hypoxic encephalopathy) by administering large doses of barbiturates (clinical anaesthesia) in combination with hyperbaric oxygenation (HBO) (Negovsky C. A., Gurvich, A. M., Zolotaryova E. C. Pocketradiologist control. Large doses of barbiturates suppress the bioelectric activity of the brain, and the method HBO technically difficult to EEG registration.

Also known is a method of treatment of the PVA, the proposed Udelson J. B. (J. N. Judelson, Y. C. St. George. Vegetative state. - Smolensk: the Academy, 2002. - S. 25), aimed at strengthening the afferent flow through the activation of polymodal sensory systems of the brain (multimodal stimulation). The disadvantage of this method is the lack of impact on the generator pathologically enhanced excitation (GPWW).

Closest to the claimed is a method of treating patients with PVS (due to the traumatic disease of the brain (CBGM)) under control of the EEG (chemical, M. L., S. Gavrilov, S., Balashov, A. N., Fradkov, C. Comprehensive assessment and differentiated treatment neuroregeneration patients with traumatic brain injury: guidelines. - L., 1990. - S. 11-16) adopted for the prototype. Depending on the clinic and EEG authors distinguish three types of patients with TBGM, two of whom are patients, appropriate clinical and EEG data, the diagnosis of PVS. 1st - normbreaking irritative type is characterized hypersynchronization EEG with the manifestation of unbalanced centrolene barbiturates and oxybutyrate Na. 2nd-hyporeactivity type is characterized by a monotonous flat EEG, and intensive therapy in this case presents common methods of stabilization of the stem circulation ("3 G" therapy, improvement of rheological properties of blood, metabolic cerebroprotective oxybutyrate Na and so on) and substitution therapy.

The disadvantages of the prototype: - the Problem of treatment of PVS is considered only in patients with TBGM and only taking into account the dynamics TBGM. Although the concept of PVA is more ambiguous and according to the 1989 definition of the American Academy of Neurology is considered as a clinical condition of complete absence of awareness of self and environment, accompanied by cycles of sleep-Wake with full or partially intact function of the hypothalamus and brain stem, and is a definite ("persistent", i.e. transient) state of mind - a way out of the patient from a coma various etiology, both traumatic and non-traumatic origin.

- Not included neurophysiological aspects of the formation of stable pathological systems (Kryzhanovsky, N. General pathophysiology of the nervous system. The leadership. - M.: Medicine, 1997. - 352 S.).

the nature and focused on the impact generated (formed) GPOW and most likely can be described as symptomatic therapy.

- Application oxybutyrate Na eliminates dynamic EEG monitoring of the functional state of the brain (FSM), especially given the influence of this drug on the bioelectrical activity of the brain (suppresses).

Is not considered the possibility of changes in the EEG and, therefore, FMF in the treatment process (i.e., the stages of the process). And registered EEG is evaluated as strictly patagonicus characteristic of a particular type TBGM.

- No specific time, clinical-neurological and electrophysiological criteria for assessing the effectiveness of therapy and its timely correction, though, and points to possible complications and prognosis based on the type TBGM based on statistics.

- The recommended treatment is not laid foundations for early rehabilitation in case of a positive dynamics.

The invention is directed to a method of treatment of patients with PVS under electrophysiological control, allowing, depending on the pattern of EEG to choose the optimal treatment tactics: from deep deprivatio (clinical anaesthesia) to multimodal stimulation (activation of visual, auditory, olfactory, tactile, and so on sensory analyser systems), and when hypersynchronized Tabellini monotonous flat EEG conduct a multimodal stimulation on the background of sedation drugs benzodiazepine series.

The invention consists in the following. In patients with PVS recorded EEG. If EEG hypersynchronization and characterized stem outbreaks of slow waves or continuous distant synchronization of theta-Delta activity, in the complex of therapeutic measures include clinical anaesthesia for edema GPUV to the disappearance of stem activity and the emergence of stable monotonous flat EEG. Clinical anaesthesia performed by standard methods with the use of drugs that have a combined effect on opioid and adrenergic antinociceptive system that allows dynamic EEG monitoring. The depth of anesthesia depends on the pattern of EEG (disappearance of hypersynchronization and other signs of irritation stem structures). The duration of anesthesia are very variable, from a few hours to several days and depends on the degree of stability GPUV. After the appearance of stable monotonous flat EEG and persistent disappearance stem activity within the "diagnostic window" tactics of treatment change and conduct a multimodal stimulation. When the original monotonous flat EEG conduct initial multimodal stimulation on the background of benzodiazepine sedation is imodules stimulation, relaxing effect GPUV on physiological bioelectric activity of the brain.

The inventive method differs from the prototype in that: - the choice of method of treatment of patients with PVS based on the principles of pathogenetic therapy and takes into account the neurophysiological aspects of pathology in accordance with the concept of academician Kryzhanovsky, N. and is aimed at suppressing GPUV; complex monitoring of patients with PVS included dynamic EEG control, allowing you to respond quickly to changes FMF and promptly correct tactics of treatment; treatment anaesthesia is carried out by the methods which allow to record the EEG; in complex treatment include multimodal stimulation, which when positive dynamics is considered as a method of early rehabilitation; - multimodal stimulation is performed under EEG control on the background of low doses of benzodiazepines, which helps to identify, maintain and consolidate positive reconstructions EEG.

- therapeutic measures have a clear focus on the restoration of neuro-psychic activity of the brain in patients with PVS regardless of etiology and maintain the electrophysiological activity of the brain at the level as close as possible and EEG conduct clinical anaesthesia and/or multimodal stimulation depending on the pattern of the recorded EEG. If there is a pattern hypersynchronization EEG in complex treatment includes therapeutic fentanyl-clonidine anaesthesia. The technique of medical anesthesia using2adrenoagonists and narcotic analgesics allows you to record EEG and maintain the electrophysiological activity of the brain at the level that is most approximate to the norm, and the depth of anesthesia is defined by the minimum dose (determined by titration), which disappears stem activity. The mean dose of fentanyl and clonidine 0.8-1.2 and 0.3-0.6 ág/kg/h, respectively. For the duration of clinical anaesthesia continues until a steady monotonous EEG and disappearance of stem activity with EEG monitoring in the background of the "diagnostic window". After obtaining a stable monotonic EEG therapeutic measures - multimodal stimulation (photic stimulation, listening to audio, active communication with relatives, massage, exercise therapy, and so on - to activate the touch sense channels) at which a positive result is the appearance of EEG stem outbreaks, often alpha-theta range - removed redundant activating influence of non-specific median structures. Particularly positive is set in a state of protective inhibition. A positive trend in the future is determined by the restoration of the bioelectrical activity of the brain in the form of increase in the amplitude of action potentials, the emergence of faster (alpha-beta) activity forms and further organization of the EEG (EEG appear rhythms, not just activity). The presence of the original monotonous flat EEG is an indication for primary multimodal stimulation on the background of the benzodiazepines. The introduction of benzodiazepines in doses not exceeding therapeutic effect of midazolam at a dose of 0.15 mg/kg, allows to weaken the influence GPUV and maintain positive adjustment EEG in case of their occurrence.

The method of treatment of patients with PVS developed and clinically tested in the Department of anesthesiology and resuscitation Department of the Polenov research neurosurgical Institute named Professor A. L. Polenov in the treatment of 18 patients. In 12 patients whose EEG parameters were maintained in the optimum range by neutralizing GPUV medical anesthesia with subsequent multimodal stimulation, there was a clear positive trend. And in 6 patients who were primary multimodal stimulation on the infusion of midazolam in a dose of from 0.1 to 0.15 mg/kg midazolam, also showed positive dynamics.

Examples - wipes the 0.10.96, on 23.01.97, with a diagnosis of PVS. Post-hypoxic encephalopathy. After asphyxia.

From the anamnesis: on September 26, 1996 fell off a cliff and was covered with sand. After 7-10 minutes dug out of the sand. Spontaneous breathing was absent. 15 minutes after artificial respiration mouth to mouth and closed cardiac massage appeared spontaneous breathing and the baby was delivered in CDH, Kirov.

When entering the Polenov research neurosurgical Institute, the condition is very severe, subcompensated on vital functions. Neurologically: level of consciousness - the persistent vegetative state (the opinion does not fix jobs does not, you saved the cycle of sleep and wakefulness, eyes narrow, D=S, reaction to light saved, oculocephalic reflexes saved periodically-floating movement of the eyeballs, a symmetrical face, lockjaw facial muscles, tongue behind the line of the teeth in the midline, pharyngeal reflex high, not independently swallows, the food probe. Tetraparesis with a marked increase in muscle tone in the flexors of the arms and the extensors of legs, each stimulation (auditory, tactile, pain) reacts Hyper to opistotonus. Periodically marked diencephalic crises, accompanied by hypertonicity flexor x covers. The spontaneous breathing, tachypnea to 26 in minutes

A comprehensive survey KG brain - moderately severe hydrops from 15.10.96 the eye - pupils narrow, reaction to light saved, the fundus of the eye without gross changes. On radiographs, lung congestion in the basal regions of both lungs.

EEG from 15.10.96 - hypersynchronization EEG recorded melanosarcoma activity unmodulated, without zonal differences, low-amplitude activity in theta-Delta range. Against this background, there are flashes of high-amplitude Delta waves, the response to photic stimulation is absent. Data EEG indicate rough diffuse changes involving stem structures diencephalon-mesencephalon level (Fig.1).

Within 20 days were conducted clinical anaesthesia under EEG control. /Drip was administered a mixture solution of fentanyl 0,005% - 6,0 + aq clonidine 0,01% - 1,0 + aq sodium chloride 0.9 per cent 500,0. Clinically noted regression of diencephalic crises.

On EEG from 24.10.96 - stable monotonous flat EEG - observed low-amplitude activity in theta-band with elements of beta activity. The presence of stem outbreaks are not registered (Fig.2).

In the complex treatment was included Polym SSA, LFC).

On EEG from 14.11.96 revealed the positive dynamics in the absence of slow waves and the emergence of chaotic groups of alpha oscillations. A particularly positive aspect is the emergence of bilateral simultaneous outbreaks of paroxysmal activity (Fig.3).

From the moment of admission to the intensive care unit the Polenov research neurosurgical Institute them. A. L. Polenov was conducted intensive therapy, including conventional management of patients with PVS, aimed at improvement of cerebral metabolism, maintaining adequate perfusion of the brain neurotransmitter therapy and antibiotic therapy. In clinical neurological dynamics gradually the boy's condition had improved.

On EEG from 04.12.96 a clear positive trend is the increase of amplitude of action potentials, the emergence of polymorphism rhythms and their organization (Fig.4).

December 20 - the boy is compensated, appeared speech production, memory returned, he began to make contact, began to walk independently. In neurological status at discharge is maintained bilateral pyramidal symptoms with a predominance in the left hand. Discharged at the place of residence with the recommendation to conduct further restorative treatment in children vosstanovit who present with a diagnosis of PVS, post-hypoxic encephalopathy.

From the anamnesis: intraoperative cardiac arrest 02.04.2002,

When translating in the Polenov research neurosurgical Institute them. A. L. Polenov the patient's condition heavy compensated for vital functions. Neurological status presents PVA. Lying with his eyes open, gaze fixes, watching the eyes of the items. Marked emotional reaction when communicating with relatives. During the application of painful stimuli tries to localize the pain. Pupils D=S, a living expression, eye movements in full. Face symmetrical, paresis of mimic muscles is not revealed. The language on the midline of the pharyngeal reflex saved. Muscle tone is very high, especially in the hands. Tetraparesis. The toning on the mixed type, mainly in the flexors. Severe symptoms of oral automatism (Marinescu-Radovici, trunk boars). Tendon and periosteal reflexes with a small asymmetry of the D<S, the symptom of bilateral Babinski, with extended reflexogenic zone (positive Oppenheim, Cedoca, Schaeffer). The abdominal reflexes are extremely low, are being rapidly depleted. Stable hemodynamics. The spontaneous breathing through a tracheostomy cannula. Somatically identified interpretarea with isothermic parameter, insipidus diabetes, redness and oiliness of the face and skin.

Using MRI from 13.05.02: median education is not shifted. The lateral ventricles are moderately dilated. Subarachnoid space is not extended. Focal changes in brain substance was not detected. The pituitary gland in sizes is not increased. Stem structure without features.

PET dated 30.05.02: a series of tomograms (15 slices) in the study of glucose metabolism revealed diffuse metabolic lesion of the cerebral cortex with the prevalence of apical departments without significant inter-hemispheric asymetrie. Relatively safe level of glucose metabolism observed in the cerebellum and brainstem, as well as in front of subcortical nuclei. Diffuse decrease the consumption of glucose in the frontal lobes is from 23% to 11% in different departments, in the parietal lobes from 20 to 10%, in the temporal lobes - 11% (relative to the cerebellum). Easy hypometabolism observed in poles and adjacent parts of the cortex of the occipital lobes, as well as in the optic tubercles, especially in the left. Conclusion: moderate post-hypoxic metabolic lesion of the cerebral cortex (the level of metabolism is reduced by 23-10%) and the phenomenon of deafferentation in visual t beta to theta waves, to maintain the proper zonal distribution rhythms. Response to photostimulation weak, almost nonexistent. Data EEG indicate diffuse moderately significant changes (Fig.5).

Made in/with the introduction of benzodiazepines (dormicum).

- With the introduction of 2.5 mg of dormicum on EEG began to emerge adjustment of rhythms in the form of the disappearance of the slower forms and the emergence of ordered beta-rhythm with elements of the alpha rhythm. When the total introduction 5 mg - further normalization of the EEG in the appearance of the correct alpha rhythm (Fig.6). 7.5 mg dormicum character EEG still, however, a significant clinical effect is the reduction of spasticity. When 10 mg - EEG and clinical effect is the same. With the introduction of 0.25 mg of anexate gradual disappearance of the alpha rhythm with the dominance of beta activity. When 0.5 mg of anexate EEG similar to the original. Recommended sedation the patient in a dose of dormicum 7.5 mg (0,12 mg/kg) when conducting a multimodal stimulation.

In complex treatment included a multimodal stimulation (photic stimulation, audio tapes, emotional, communication with relatives, massage, exercise therapy).

On EEG from 23.05.02 - registered rapid activity, mainly beta - band, with the advent of Alfie during rhythmic photostimulation - theta waves. Data EEG indicate diffuse moderately expressed changes (changes in the background/introduction 2.5 mg of dormicum), irritatio diencephalic structures (Fig.7).

From the moment of admission to the intensive care unit the Polenov research neurosurgical Institute them. A. L. Polenov was conducted intensive therapy, including conventional management of patients with PVS, aimed at improvement of cerebral metabolism, maintaining adequate perfusion of the brain neurotransmitter therapy. Also conducted therapy aimed at the destruction of GPOW (multimodal stimulation on the background of 7.5 dormicum/etc ), acupuncture, therapeutic massage, therapeutic exercise, physical therapy and antibiotic therapy. Proper balanced enteral therapy. The tracheostomy was removed, tracheostomy course earned. On the background of therapy showed a significant positive trend for EEG, positive changes in neurological status. Sick in the mind, pin assignments, " says single words. On examination reacts adequately. Stored emotional lability. Pupils D=S, the expression alive. Face symmetrical. Tetraparesis with increased tone in the mixed type, the maximum increased tone in the right raquy). Stable hemodynamics. The spontaneous breathing, adequate.

On EEG from 10.06.02 - recorded the activity of alpha-, beta-ranges, intermittent theta waves. The positive dynamics in the form of the disappearance of trunk irritation and, most importantly, the emergence of rhythm (mainly alpha-rhythm) is more resistant to the left, while on the right is also the organization of the rhythm (Fig.8).

Using the proposed method enables the treatment of patients with PVS under EEG control and depending on the pattern of the recorded EEG timely adjustments to unfavorable changes in the electrophysiological activity of the brain and maintain it at optimal physiological level by suppressing the pathological activity of brainstem structures medical anesthesia and/or conduct a multimodal stimulation on the background of low doses of benzodiazepines.

The method allows to create favorable conditions for the normalization of the bioelectrical activity of the brain, restoration of physiological regulatory functions of the brain, weakening and destruction GPUV and in General for recovery of neuro-psychic activity and improve treatment outcomes of patients with PVS.

Claims

1. Treatment b is decomposing the, that correction of the functional state of the brain to change its bioelectric activity, and on the background of EEG registration conduct clinical anaesthesia for opioid analgesics and2-adrenoagonists followed multimodal stimulation or carry out a multimodal stimulation on the background of the introduction of the benzodiazepines.

2. The method according to p. 1, wherein when the pattern hypersynchronization EEG conduct clinical anaesthesia.

3. The method according to p. 2, characterized in that therapeutic anaesthesia until stable monotonous flat EEG and termination of stem activity.

4. The method according to PP.2 and 3, characterized in that when the pattern is stable, monotonous flat EEG and absence of stem activity conduct a multimodal stimulation.

5. The method according to p. 1, characterized in that when the original monotonous flat EEG multimodal stimulation is performed on the background of the introduction of benzodiazepines in doses not exceeding therapeutic effect of midazolam at a dose of 0.15 mg/kg

 

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