Functional Activity of the Autonomous Nervous System at Different Levels of Consciousness in Patients with a Brain Damage

Цель — оценка уровня сознания у пациентов с повреждением головного мозга на основе электрофизиологического обследования функционального состояния автономной нервной системы путем регистрации параметров вариабельности ритма сердца. Материал и методы исследования. В исследование включили 77 пациентов на 20-50-е сутки после черепно-мозговой травмы, аноксического повреждения, последствий острых нарушений мозгового кровообращения. В качестве критериев нормы и патологии активности автономной нервной системы (АНС) приняли следующие параметры вариабельности ритма сердца (ВРС) для 5-минутной записи: парасимпатическую гиперактивность (гипервагусное состояние) с 95% доверительными интервалами принимали в пределах значений для SDNN (стандартное отклонение от средней длительности всех синусовых R—R интервалов), [41,5–149,3 мс]; для rMSSD (среднеквадратичное отклонение разности двух смежных отсчетов R—R кардиоинтервалов в мс), [42,4–175,0 мс]; для pNN50% (доля в % соседних синусовых R—R интервалов, которые различаются более чем на 50 мсек), [8,14–54,66%]; для SI (стресс-индекс напряжения Баевского), [0—80 нормализованных единиц н. е.]; симпатическую гиперактивность принимали в пределах значений для SDNN [4,54—13,30 мс]; для rMSSD [2,25—5,77 мс]; для pNN50% [0—0,109%]; для SI >900 н. е.; Норма параметров ВРС принималась в пределах значений для SDNN [13,31—41,4 мс]; для rMSSD [5,78—42,3 мс]; для pNN50% [0,110—8,1%]; для SI [80—900 н. е.]. Для верификации гипервагусного состояния, симпатической гиперактивности или нормы в указанных пределах принимали 3 из 4-х параметров. Результаты. У 40 (51,9%) пациентов из обследованных 77-и после повреждения головного мозга параметры функциональной активности АНС находились в зоне патологических значений. Симпатическую гиперактивность выявили у 34-х пациентов и в 6-ти случаях зафиксировали гипервагусное состояние. Патологические параметры HRV выявили у 80% пациентов при тяжелых формах нарушения сознания (вегетативное состояние, кома), а при норме сознания — обнаружили лишь у 20% пациентов. Заключение. Компьютерный анализ вариабельности сердечного ритма — необходимый элемент обследования пациентов с различными уровнями сознания после повреждения головного мозга травматического и нетравматического генеза. Частота патологических изменений со стороны функционального состояния автономной нервной системы достоверно нарастает в группах пациентов от нормального уровня сознания к состоянию минимального сознания, вегетативному состоянию и коме. Основным вариантом патологии АНС в группах пациентов находящихся в состоянии минимального сознания, вегетативном состоянии и коме является симпатическая гиперактивность.


Introduction
Currently used scales of assessment of consciousness in patients with brain injury of a traumatic and non-traumatic genesis (Glasgow, Four) are applied to predict mortality [1][2][3][4][5][6][7][8].However, only patients' behavioral reactions (speech, movements, eye opening, reflexes) are evaluated by these scales.At the same time, it is well known that a balanced adaptive reaction of the autonomous (vegetative) nervous system is the key to maintaining the stability of the organism in the development of critical conditions, including cerebral insufficiency [9][10][11][12][13].A pathology of this functional structure of the body leads to the development of systemic complications, impairment of systemic and regional oxygen homeostasis, regulation of vascular tone, secondary brain damage, nutritive insufficiency, problems of verticalization and weaning [14,15].
The purpose of this study was to assess the level of consciousness in patients with a brain damage on the basis of electrophysiological examination of the functional state of the autonomous nervous system (ANS) by recording parameters of the HRV.
Based on the nosological entities, the patients were distributed as follows: consequences of a craniocerebral injury (CCI) (n=45); consequences of acute disorders of cerebral circulation (stroke), (n=6); consequences of anoxic brain injury (n=10); consequences of subarachnoid hemorrhage (n=5); consequences of removal of a tumor or arteriovenous malformations of the brain (n=11).
6) arousal (activation) function (0-3 scores).The level of consciousness ranges from 0 (coma) to 23 (state of clear consciousness) according to this scale scoring.Details of the clinical application of the CRS-R scale and its definition are given by Giocino et al. ( 2002) [16].
There were 4 groups of patients (Table 1).
The functional state of the autonomous (vegetative) nervous system was assessed in all groups on the basis of a computer analysis of the HRV.[17].The evaluation of HRV was performed by the Polyspektr-8 EX apparatus (Neurosoft, Russia) with the protocol of the wireless Bluetooth connection between the cardioanalyzer and a personal computer.In each study period, at least 300 R-R intervals were analyzed (the HRV parameters were calculated according to corresponding formulas of distribution of cardiac intervals).The following HRV parameters were determined: SDNN -standard deviation of normal to normal R-R intervals, in ms; rMSSD-root-mean-square of the successive normal sinus R-R interval difference, in ms; pNN50% -percentage of successive normal sinus R-R intervals >50 ms; SI -Baevsky stress-index in n.u.; LF/HF-low frequency/high frequency ratio in n.u.; VLF (very low frequency spectrum) in ms 2 ; LF (low frequency spectrum) in ms 2 and %; HF (high frequency spectrum) in ms 2 and %.The following parameters of the heart rate variability (HRV) were accepted as criteria of norm and pathology of the ANS activity : parasympathetic hyperactivity (hypervagal state) with 95% confidence intervals was taken within the accepted values for SDNN, [41.5-

Results and Discussion
Parameters of the level of consciousness obtained according to the Glasgow, Four, and Giocini scales are presented in Table 2.
It is obvious that the assessment of all scales demonstrate a significant difference between the state of the normal consciousness and the state of the min-
In 40 (51.9%) of 77 patients examined after a brain damage resulting from the craniocervical injury and stroke, ANS functional activity parameters were within the range of pathological values [18].The sympathetic hyperactivity was identified in 34 patients, and in 6 cases the parasympathetic hyperactivity was diagnosed.
Pathological parameters of the HRV (Table 3) were found in most cases of severe forms of impairment of consciousness (vegetative state, coma) in 32 (80%) patients; and in the case of less severe impairment of consciousness (minimal consciousness) and in the case of normal consciousness they were found only in 20% of patients.The inverse dependence was found in the analysis of normal values of HRV: severe forms of impairment of consciousness (vegetative state and coma) were found in only 12 (32.4%)patients; and in the case of less severe forms of impairment of consciousness (minimal consciousness, normal consciousness), normal parameters of HRV were found in 25 (67.6%)patients.In the vast majority of cases, normal values of the ANS functional activity were found in patients with a normal level of consciousness.For example, in the group 1 (normal level of consciousness, n=10), 90% of patients presented normal HRV, and only 1 patient (10%) presented sympathetic hyperactivity.In the group 2 (state of minimal consciousness,

Parameters Values of parameters in groups
The traumatic brain injury (TBI) and an acute cerebral circulation disorder are among the leading causes of death and severe disability worldwide [19].At the same time, the neurological evaluation is a necessary element of differentiation of patients in the intensive care unit.The assessment of the level of consciousness using Glasgow, Four, and Giocini scales involves the calculation of various symptoms in response to the environmental stimuli (pain, speech, light, etc.).The subjective nature of these techniques is recognized by many researchers and depends on doctor's experience.In order to increase the accuracy, the average result based on scoring of patient's level of consciousness by several healthcare professionals is often calculated, which complicates the overall interpretation of the result [2].In addition, taking into account the known problems of these scales, it is proposed to modify them by excluding the evaluation of the motor deficiency (a so-called binary method of application of the Glasgow scale) [20].Lack of registration of biochemical, hematological, and electrophysiological parameters that limits the understanding structural and functional pathological changes in the brain poses a significant problem in determining the level of consciousness from the standpoint of neurological and psychological approaches.At the same time, there are data on the autonomous dysfunction in a brain damage that may serve as an m marker of the state, outcome, and functional independence of patients.In a study of Esterov D. et al. (2017) it was shown that the autonomous dysfunction in a brain injury caused impairment of the organ complex function and increases mortality rates [11].The authors found that the manifestations of the ANS dysfunction (on the basis of the analysis of the heart rhythm variability) are persisted even after correction of clinical symptoms of CCI.Hilz M. J. et al.  [13].

Заключение
Компьютерный анализ вариабельности сердечного ритма -необходимый элемент обследования пациентов с различными уровнями сознания после повреждения головного мозга травматического и нетравматического генеза.assessed the HRV in patients with mild, moderate and severe degrees of brain damage [12].The authors investigated the spectral characteristics of the HRV determining the sympathetic high-frequency spectrum (LF) and parasympathetic low-frequency spectrum (HF), the LF/HF ratio, normalized units of the LF and HF HRV spectrum.The groupsincluding patients at a rest and during verticalization were compared.The authors found a correlation between the parameters of the autonomous nervous system and the consciousness level determined by a Glasgow coma scale (P<0.05).Glasgow coma scale correlated positively with LF, LF/HF whereas negative correlation with HF was found.Mirow S. et al. (2016) showed that the analysis of the HRV allows assessing the coordination of structural (anatomical) and functional systems of the body [21].The HRV parameters were summarized and compared to the neurological status.Pathological nystagmus correlated with a 25% decrease of SDNN values.The increase in sympathetic modulation associated with the level of anxiety: a 19-percent growth of LF/HF was noted.These data demonstrate the need to assess ANS dysfunctions while examining patients after CCI.Osteraas N.D. et al. ( 2017) in a review article have shown the clinical value of assessment of interaction of the ANS and cardiovascular systems [13].
Stress-related cardiomyopathy caused by impairment of the brain-heart interconnection occurs in many conditions and especially in the brain injury leading to sympathetic hyperactivity.The concept of «paroxysmal sympathetic hyperactivity» has been introduced, which occurs very commonly in patients after brain injuries (PSH, Paroxysmal sympathetic hyperactivity).In PSH, there is a cascade of simultaneously occurring adverse symptoms: tachycardia, tachypnea, hypertension, fever, muscle dystonia, and hyperhidrosis, which together worsen the somatic status of patients, neurological prognosis, and rehabilitation.Patients with symptoms of PSH have a more severe nutritional status, more often develop infectious complications, stay in the intensive care units for a longer period of time, and exhibit a significantly higher mortality rate [22][23][24][25].PSH causes a significant impairment of homeostasis and leads to a secondary, cumulative brain damage.It is sympathetic hyperactivity that is the main pathological change in the ANS functional activity in patients in the vegetative state and in coma.It is obvious that the assessment of dysfunction of the ANS is a necessary and compulsory element of the examination of patients after a craniocerebral injury, anoxia of the brain, and consequences of perioperative complications.

Conclusion
The computer analysis of the HRV is an obligatory element of examination of patients with different DOI:10.15360/1813-9779-2018-2-4-12
The frequency of changes in the functional state of the ANS in patients has been significantly and gradually increasing starting from the group with patients exhibiting normal level of consciousness to groups of patients with minimal consciousness, vegetative state, and coma.
A sympathetic hyperactivity, a precipitous enhancement of sympathetic ANS, is the main type of ANS pathology in the groups of patients with minimal consciousness, in the vegetative state and coma.
The assessment of the ANS function allows to monitor the level of consciousness of patients after traumatic and non-traumatic brain injury.