Prediction of the functional outcome of cerebral ischemic supratentorial stroke acute period on the basis of spectral analysis of the brain bioelectrical activity

Materials and methods. Prospective, cohort and comparative study was conducted among 103 patients in CISS acute period (61 men and 42 women, mean age was 67.7 ± 0.8 years). Electroencephalographic study was conducted on the 2nd–3rd day of the disease with the use of 19-channel electroencephalographic scanner. The values of absolute spectral rhythm power of delta (0.5–4.0 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–35 Hz), theta1 (4–6 Hz), theta2 (6–8 Hz), alpha1 (8–10 Hz), alpha2 (10–13 Hz), beta1 (13–25 Hz) and beta2 (25–35 Hz) bands in the affected hemisphere (AH) and intact hemisphere (IH) were determined. The relative spectral rhythm power (RSRP), fronto-occipital rhythm gradient (FORG) and the severity of interhemispheric rhythm asymmetry (IHRA) were calculated. The functional outcome of the disease acute period was assessed on the 21st day on the basis of the modified Rankin Scale (mRS), while the value of mRS score >3 was considered as an unfavourable functional outcome.


Introduction
Cerebral ischemic supratentorial stroke (CISS) as the most common form of cerebrovascular pathology is a global problem of modern times. Its special medical and social significance is due to the leading positions in the structure of death and disability causes in most countries of the world [1][2][3]. One of the most appropriate means to improve the effectiveness of treatment activities in patients with CISS is a differentiated approach development for the optimal tactics selection on the basis of an individual prognosis [4][5].
All of the mentioned above justifies the necessity of brain damage severity objectification at the onset of CISS. Electroencephalography (EEG) is one of the most informative methods to study the brain functional state. This method is highly sensitive to changes in brain bioelectrical activity that are induced by acute focal ischemia [6][7][8].
In combination with a millisecond time resolution, that is impossible to be used in diffusion-mediated magnetic resonance imaging and positron emission tomography [9], it explains the fact that EEG has been used for more than 40 years for cerebral ischemia detection during carotid surgery [10]. Additional advantages of the method are: noninvasiveness and absence of contraindications. Quantitative (spectral) analysis of EEG pattern allows increasing the diagnostic informative value of the method [11][12][13][14]. At the same time, the unified criteria for the determination of the short-term functional prognosis of CISS acute period outcome, which take into consideration the results of spectral analysis of the brain spontaneous bioelectrical activity, are currently absent, and the purpose of this study was to determine the most informative parameters of spectral analysis of the electroencephalographic pattern for the functional outcome of cerebral ischemic supratentorial stroke acute period prediction.

Materials and methods
Prospective, cohort and comparative study was conducted among 103 patients in CISS acute period (61 men and 42 women, mean age was 67.7 ± 0.8 years), who were hospitalized within the first 24 hours from the onset of the disease and who did not undergo thrombolytic therapy.
CISS pathogenic subtype was determined in accordance with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria [15]. Clinical and neurological study included the neurological deficit level assessment using National Institute of Health Stroke Scale (NIHSS) in acute period dynamics. The visualization of cerebral structures was made with the help of CT scanner "Siemens Somatom Spirit" (Germany). The lesion size and the displacement of brain median structures were assessed.
The study excluded patients with acute cerebral circulation disorders, craniocerebral injury and epileptic seizures in the anamnesis, combined with the cerebral hemorrhage, hemorrhagic transformation of brain infarction, oncologic and/or decompensated somatic pathology.
Electroencephalographic study was conducted on the 2 nd -3 rd day of the disease with the use of 19-channel Ключевые слова: инфаркт мозга, электроэнцефало графия, прогноз. electroencephalographic scanner "NeuroCom Standard" (XAI-Medica, Ukraine). Electrodes were placed in accordance with the international system "10-20". The oculographic, rheographic and electrocardiographic artifacts were rejected with the use of software tools and the Independent Component Analysis (Blind Sourse Separation Technology) procedure. The 60-second epochs after artifact rejection were selected for the spectral analysis. The spectral analysis was carried out with the help of fast Fourier transform method. The values of absolute spectral rhythm power of delta (0.5-4 Hz), theta (4-8 Hz), alpha (8)(9)(10)(11)(12)(13), beta , theta1 (4-6 Hz), theta2 (6-8 Hz), alpha1 (8-10 Hz), alpha2 (10-13 Hz), beta1 (13-25 Hz) and beta2 (25-35 Hz) bands in the affected hemisphere (AH) and intact hemisphere (IH) were determined. The relative spectral rhythm power (RSRP) values of the specified frequency bands (%) were calculated. To quantify the zonal differences of the rhythm distribution within AH and IH, the values of the fronto-occipital rhythm gradient (FORG) were calculated using the following formula: FORG = (ASRP in the frontal region -ASRP in the occipital region) / (ASRP in the frontal region + ASRP in the occipital region). The severity of interhemispheric rhythm asymmetry (IHRA) was determined on the basis of the following formula: IHRA = (ASRP in the AH -ASRP in the IH) / (ASRP in the AH + ASRP in the IH).
All patients received standard therapy in accordance with the Unified Clinical Protocol for medical care "Ischemic stroke (urgent, primary and secondary (specialized) medical care, medical rehabilitation)", approved by the order of the Ministry of Health of Ukraine №604 of August 03, 2012. The functional outcome of the disease acute period was assessed on the 21st day on the basis of the modified Rankin Scale (mRS), while the value of mRS score > 3 was considered as an unfavourable functional outcome, whereas mRS score ≤3 was considered as a favourable one.
Statistical analysis of the results was carried out using the software Statistica 6.0 (StatSoft Inc., USA, series number AXXR712D833214FAN5) and MedCalc (version 16.4). The distribution normality of the studied traits was estimated in accordance with the Shapiro-Wilk criterion. Descriptive statistics are presented in the form of M ± m for values with normal distribution and in the form of median (Me) and interquartile range (IQR) for parameters with nonnormal distribution. To determine the intergroup differences in the studied characteristics, the Mann-Whitney criterion was used. Factors that had significant predictive value in the univariate logistic regression analysis were step by step included in the multivariate model in order to determine independent predictors. The cut-off points for independent predictors with the optimum sensitivity (Se) and specificity (Sp) were determined on the basis of the ROC analysis. Statistical significance of results was defined as a P value <0.05.
The results of EEG pattern spectral analysis in patients with CISS on the 2 nd -3 rd day of the disease are shown in Table 1 and Table 2.
The analysis of EEG pattern rhythm structure (%) was made in patients with CISS on the 2 nd -3 rd day of the disease versus the acute period outcome of the disease ( Table 2).
The presented data shows that patients with an unfavourable functional outcome of CISS acute period had higher RSRP of delta band on the 2 nd -3 rd day of the disease The inversion of negative FORG of alpha, alpha1 and alpha2 bands in the AH was representative of patients with unfavourable functional outcome of CISS acute period, as well as a positive tendency of FORG of delta, beta, beta1 bands on the 2 nd -3 rd day of the disease, whereas the reduction of negative FORG of alpha2 band was detected in the intact hemisphere ( Table 3).
Patients with CISS and unfavourable functional outcome on the 2 nd and 3 rd day of the disease had IHRA of alpha, alpha1 and alpha2 bands, which was proved by negative values of corresponding indexes ( Table 4).
Parameters of EEG pattern spectral analysis were determined on the basis of the univariate logistic regression analysis. They were associated with the functional outcome of CISS acute period. The frequency distribution of unfavourable functional outcome of the CISS acute period in terms of RSRP of delta band in the IH, FORG of alpha band in the AH and IHRA of alpha band is shown in Table 6.
As a result, the RSRP of delta band in the IH >18.

Discussion
Thus, on the basis of the EEG patterns spectral analysis comparative analysis it was determined that patients with the unfavourable outcome of CISS acute period on the 2 nd -3 rd day of the disease had a higher severity of bioelectric brain activity impairment in affected and intact hemispheres. This cohort of patients had higher values of RSRP of delta and theta bands and lower levels of RSRP of alpha and beta bands, whereas the increase in demonstrated changes severity was in the affected hemisphere. In addition, patients with the unfavourable outcome of CISS acute period on the 2 nd -3 rd day of the disease had ipsilateral reduction of zonal rhythm differences of alpha, alpha1 and alpha2 bands, which was due to a more severe depression of the absolute spectral power of the specified rhythms in caudal parts of the affected hemisphere. It was accompanied by the generation of interhemispheric asymmetry of absolute spectral rhythm power of alpha band and complied with the results of other studies. Thus, in accordance with S. P. Finnigan et al. (2007) sub-acute delta/alpha power ratio (R = 0.91, P < 0.001) and relative alpha power (R = -0.82, P < 0.01) were significantly correlated with 30-day NIHSS score [16]. The study of R. V. Sheorajpanday et al. (2011) determined that the EEG pairwise derived Brain Symmetry Index (pdBSI) was significantly correlated with the modified Rankin Scale (mRS) score at month 6 (R = 0.46, P < 0.0005) [17]. In accordance with the data of X. Xin et al. (2017) poor functional outcomes were associated with higher BSI [18]. Our research studied the prognostic value of interhemispheric different frequency bands asymmetry indexes, while independent association with the functional outcome of CISS acute period was only determined for IHRA of alpha band. The prognostic value of FORG of alpha band in the AH on the 2 nd -3 rd day of CISS was proved, which confirms the advisability to define not only IHRA of alpha band, but also alpha-rhythm zonal differences in order to prognosticate the functional outcome of the disease acute period.
It should be noted, that the results of our study revealed the presence of RSRP delta-range of IH in the spectral of independent predictors of the unfavourable functional outcome of CISS acute period. It was also determined that this index has a higher informative value than IHRA of alpha band and the FORG of alpha band in the AH for the determination of a short-term functional prognosis. The obtained data complies with the results of other studies. Thus, in the study of G. Assenza et al. (2013), an increase in contralesional delta band power was mediated by interhemispheric disconnection providing negative prognosis in acute stroke [19]. In accordance with M. E. Wolf et al. (2017), generalized (but not focal) slowing were associated with clinical deterioration [20]. Thus, the intact hemisphere dysfunctional severity is also associated with the functional outcome of CISS acute period.
We determined the following cut-off points for the values of these indexes with the optimal sensitivity and specificity level for the functional outcome of CISS acute period prognosis: RSRP of delta band in the IH > 18.     The perspective for the further scientific research is the criteria of the unfavourable vital outcome of CISS acute period elaboration on the basis of EEG pattern spectral analysis.