and the State of the Autonomic Nervous System in Patients with Chronic Impairment of Consciousness Due to Severe Brain Damage

исследования: изучить пассивной ортостатической пробе у пациентов с вследствие тяжелых и их в процессе. Материалы и методы. В исследование включили 30 пациентов длительными сознания, вызванными тяжелыми (группа Purpose of the study: to examine sensibility of baroreceptors and the autonomic nervous in the passive orthostatic test in patients with chronic impairment of consciousness due to severe brain damage and determine their role in the rehabilitation process. Materials and methods. The study included 30 patients with long-term impairment of consciousness due to severe brain damage (group 1), 10 of them being in the vegetative state (VS) and 20 being in the minimally conscious state (MCS). Craniocerebral trauma was the main cause of severe damage in that group (53% of patients). The comparison group included 24 patients with focal neurological symptoms caused predominantly — 79.2% of cases — by cerebrovascular disorders (group 2). The control group (group 3) consisted of 22 healthy volunteers of a comparable age. All measurements were done with the help of a Task Force Monitor 1030i (CNSystem, Austria) in the course of passive orthostatic test at 0°–30°–60°–0°. Changes in the power of low-frequency (LFS) and high-frequency spectrum (HFS) of heart rate variability and baroreceptors sensibility (BRS) were analyzed. Statistical analysis was carried out using Statistica-10 software. Signiﬁcance of inter-group diﬀerences on unrelated samples was determined by the Mann–Whitney U -test. Diﬀerences between groups were considered signiﬁcant at P (cid:10) 0.05. Results. Maximal background values of BRS were found in the control group. In group 1 and 2 patients, considerable decrease of that index was noted, which was proportional to the brain damage severity. Similar dynamics was observed for the indices of autonomic nervous system sensibility (LFS and HFS). The main trend of orthostatic changes of BRS, LFS, and HFS was characterized by progressive decrease of the indices with increase of the patients’ angle of tilting and their return to the baseline level after the patients were put back into the horizontal position. 4 patients of group 1 (14%) displayed signs of orthostatic disorders upon tilting to 30°: in 3 cases, orthostatic hypotension was observed, and in one case the postural orthostatic tachycardia syndrome (POTS) was diagnosed. Those patients diﬀered by lower BRS and higher sympathetic system activity (LFS) vs. the same indices of other patients in that group. Conclusion. Patients with chronic impairment of consciousness during the post-comatose period after a severe brain damage display a signiﬁcant decrease of baroreceptors sensibility and autonomic nervous system disorders manifesting in signiﬁcantly lower activity of the sympathetic and parasympathetic systems. The prominence of such disorders is associated with brain damage severity. Their risk of developing orthostatic hypotension during tilting towards a vertical position is higher in patients who have lower baroreceptors sensibility, and this should be taken into account beginning the process of their verticalization.

Purpose of the study: to evaluate the sensitivity of baroreceptors and the autonomic nervous system during passive orthostatic test in patients with chronic impairment of consciousness due to severe brain damage and determine their role in rehabilitation.

Materials and Methods
The study included 30 patients with long-term impairment of consciousness caused by severe brain damage (group 1), 10 of which being in VS and 20 -in MCS. Patients with focal brain damage (n=24) (group 2) were fully conscious with local neurological symptoms being predominant in their clinical presentation. Twenty two apparently healthy volunteers of comparable age (53.4±6.6 years) were also examined (group 3). The condition of patients and volunteers was evaluated clinically and by biochemical tests. Clinical characteristics of the groups are described in table 1.
Statistical analysis of data obtained was carried out using Statistica-10 software package. The analysis included a check for distribution normality using the Kolmogorov-Smirnov d-test, which revealed far from normal distribution of BRS and ANS. To determine significance of intergroup differences, non-parametric analysis of unrelated samples using the Mann-Whitney U-test was carried out. Differences were considered significant at P 0.05. The descriptive statistics was presented as means (M) and standard deviations (SD) (table 1), also as median (Med) and quartile (25%; 75%) values of parameters (tables 2-4).

Results and Discussion
The study demonstrated significant differences in BRS between groups of patients after severe or focal brain damage and apparently healthy volunteers (table 2).
Analysis of background BRS values in horizontal position revealed a direct link between brain damage severity and the degree of a BRS decrease.
Maximal BRS values were observed in group 3 that included healthy volunteers (BRS up Med = 9.8 msec./mm Hg); in patients of groups 1 and 2 BRS values were lower (Med = 6.22 and 9.07, respectively, P 0.05, cm, table 2). Comparison of BRS response to ABP decrease (BRS down) in patients of different groups showed significance of differences between groups 1-3 and 2-3. During passive orthostatic test with tilt angles of 30° and 60°, progressive decrease of BRS was observed in all three groups of subjects, but the correlations of those indices in the subjects of three groups remained the same: maximal values were typical for the subjects of group 3, minimal values remained for group 1, and intermediate values of BRS were observed in subjects of group 2. At all stages of the passive orthostatic test procedure, significance of differences was evident only between groups 1 and 3 (see table 2). There was a significant difference in the index values bew w w . r e a n i m a Клинические исследования и практика ров в минуту). После регистрации этих нарушений исследование немедленно прекращали, и пациента возвращали в горизонтальное положение. Так как измерения параметров гемодинамики осуществляли в реальном масштабе времени, своевременная диагностика описаных нарушений во всех случаях позволяла избежать развития гипоперфузии головного мозга и ухудшения состояния пациентов.
Анализ фоновых значение ЧБР в горизонтальном положении выявил прямую зависимость между тяжестью повреждения головного tween groups 1 and 2 only in case of 60° tilt. Upon return to the horizontal position (horizontal position 2), the trend towards increase of measured parameters and return to the baseline was noted in all three groups, previous intergroup differences being maintained.
Significant intergroup differences were found during the analysis of heart rate variability (table 3).
The findings revealed significant disturbances of the autonomic nervous system in patients with severe brain damage (group 1) and local brain damage (group 2) in horizontal position 1, which manifested in significant reduction of the power of lowfrequency (LFS) and high-frequency (HFS) spectra. The highest activity of the sympathetic system (LFS) and parasympathetic system (HFS) was observed in the control group of apparently healthy volunteers (LF Med = 137.05, HF Med = 162.4); in group 2, those indices were reliably lower both in the horizontal position and at all stages of the passive orthostatic test with the exception of HFS at 60° up tilt (P=0.37) (table 3). The lowest LFS and HFS were recorded in patients with consequences of severe brain damage (group 1). The difference between those indices and findings of group 2 patients was reliable at all stages of the passive orthostatic test procedure with the exception of one index -HFS in horizontal position 2, P=0.06. The pattern of intergroup differences almost did not change at different angles of up tilt of the head. The main trend of orthostatic changes in the autonomic nervous system indices of patients was characterized by even more prominent decrease of the power Полученные данные выявили значительные нарушения автономной нервной системы у пациентов с тяжелыми повреждениями of LFS and HFS; at that, if in group 2 patients, that trend was traced to increase of the angle of tilt to 60°, in group 1 patients it was observed to 30° angle only. In healthy volunteers (group 3), that trend manifested insignificantly. Within 10 minutes of return of patients to the horizontal position (2), all indices of the autonomic nervous system of subjects of all groups reached the baseline values. Reaching of a relative stability of hemodynamics at the background of quite decreased BRS up and considerable (almost two-fold) decrease of BRS, and significant reduction of sympathetic nervous system activity (LFS) in patients with chronic impairment of consciousness after severe brain damage compared to healthy volunteers is a surprising fact.
It was particularly interesting to determine peculiarities of orthostatic changes of parameters under study in patients with orthostatic circulatory disorders detected in the course of this study (table 4).
In patients with orthostatic disorders of hemodynamics in the horizontal position, extremely low BRS (3.11 msec./mm Hg) was found, which was lower than in other patients of group 1 (6.9±3.2 msec./mm Hg). Due to a small size of the sample of patients with orthostatic disorders (n=4), it was not possible to check the significance of differences in the indices of BRS and autonomic nervous system activity between patients who had such disorders vs. patients who did not have them. The same reason made it necessary to pool BRS up and BRS down data to calculate BRS mean values. The sympathetic nervous system activity (LFS) in patients with orthostatic disorders was higher, based on me-
У пациентов с ортостатическими нарушениями гемодинамики в горизонтальном положении выявлена экстремально низкая ЧБР (3,11 мсек/мм рт. ст.), которая была ниже, чем у остальных пациентов группы 1 (6,9±3,2 мсек/мм рт. ст.). Ввиду малой выборки группы пациентов с ортостатическими нарушениями (№ 4) проверить статистическую достоверность раз-dian values, than in patients who did not have such disorders (Med = 20.52 vs. 8.5 msec. 2 ). Upon 30° tilt, in patients with orthostatic disorders, BRS values remained extremely low while LFS power increased two-fold in the absence of significant changes of HFS. Prior to syncope development, LFS increase takes place due to a brief rise of sympathetic system activity followed by its decrease, bradycardia development, and ABP downfall [30]. Findings of severe patients with multiple injuries evidence significant decrease of activity of the sympathetic nervous system (LFS) and BRS. It has been shown that BRS decrease down to 4.4±1.5 msec./mm Hg was reliably associated with adverse outcome of the disease in contrast to the value of that index equal to 8.7±2.2 msec./mm Hg in patients with favorable prognosis [31]. Importantly, BRS figures in group 1 patients were similar to the figures of newborns on weeks 2-4 after the birth. In newborns, this index increased 2-3-fold by the sixth month of life [32]. Such similarity can be explained by 'immaturity' of sympathetic baroreflex mechanism in newborns that gradually adjusts its function ('matures') in newborns in the course of ontogenesis. In patients, low BRS figures are related to sympathetic baroreflex dysfunction due to severe brain damage. It can be assumed that in patients with severe diffuse brain damage involving stem structures, regulation of blood circulation returns to a phylogenetically more ancient level, which, in ontogenesis, corresponds to the perinatal level. Further investigations are necessary to verify the hypothesis.

Conclusion
The data deminstrate that patients with chronic impairment of consciousness during the post-comatose period after severe brain damage display a significant decrease of baroreceptors sensitivity and autonomic nervous system disorders manifesting in considerably lesser activity of the sympathetic and parasympathetic systems. The degree of such alterations correlates with a brain damage severity. The risk of developing orthostatic hypotension during verticalization is higher in patients with lower baroreceptors sensitivity, which is necessary to consider from the very beginning of the process of verticalization patients.  Таблица 4. Показатели низкочастотного спектра изменений R-R интервалов, высокочастотного спектра изменений R-R интервалов и чувствительности барорецепторов у пациентов с ортостатическими нарушениями гемодинамики (n=4). Table 4. Parameters of low-frequency spectrum of R-R intervals, high frequency spectrum of R-R intervals and baroreceptor sensibility in patients with orthostatic circulatory disorders (n=4).
Note. BRS Mean -mean baroreceptor sensibility to increasing of blood pressure between BRS up and BRS down. Примечание. BRS Mean -средние значения чувствительности барорецепторов между BRS up и BRS down.