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Funder: Università degli Studi di Siena, BACKGROUND: Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality.. METHODS: In our previous work, we introduced a novel measure of brain-heart interaction termed brain-heart crosstalks (ctnp), as well as two additional brain-heart crosstalks indicators [mutual information ([Formula: see text]) and average edge overlap (ωct)] obtained through a complex network modeling of the brain-heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package. RESULTS: A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain-heart crosstalks varied (mean 58, standard deviation 57). The Kruskal-Wallis test comparing brain-heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for [Formula: see text], 0.005 for ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: - 0.13 for ctnp (p value 0.04), - 0.19 for ωct (p value 0.002969) and - 0.09 for [Formula: see text] (p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16-29, 30-49, 50-65, and 65-85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16-29, 50-65, and 65-85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain-heart crosstalks and mortality was also confirmed. CONCLUSIONS: The presence of a negative relationship between mortality and brain-heart crosstalks indicators suggests that a healthy brain-cardiovascular interaction plays a role in TBI.

OBJECTIVES: The detection of increasing intracranial pressure (ICP) is important in preventing secondary brain injuries. Before mean ICP increases critically, transient ICP elevations may be observed. We have observed ICP transients of less than 10 min duration ,which occurred simultaneously with transient increases in heart rate (HR). These simultaneous events in HR and ICP suggest a direct interaction or communication between the heart and the brain. METHODS: This chapter describes four mathematical methods and their applicability in detecting the above heart-brain cross-talk events during long-term monitoring of ICP. RESULTS: Recurrence plots, cross-correlation function and wavelet analysis confirmed the relationship between ICP and HR time series. Using the peaks detection algorithm with a sliding window approach we found an average of 37 cross-talk events (± SD 39). The number of events detected varied among patients, from 1 to more than 150 events. CONCLUSION: Our analysis suggested that the peaks detection algorithm based on a sliding window approach is feasible for detecting simultaneous peaks, e.g. cross-talk events in the ICP and HR signals.

Background We present a multiplex network model for the analysis of Intracranial Pressure (ICP) and Heart Rate (HR) behaviour after severe brain traumatic injuries in pediatric patients. The ICP monitoring is of vital importance for checking life threathening conditions, and understanding the behaviour of these parameters is crucial for a successful intervention of the clinician. Our own observations, exhibit cross-talks interaction events happening between HR and ICP, i.e. transients in which both the ICP and the HR showed an increase of 20% with respect to their baseline value in the window considered. We used a complex event processing methodology, to investigate the relationship between HR and ICP, after traumatic brain injuries (TBI). In particular our goal has been to analyse events of simultaneous increase by HR and ICP (i.e. cross-talks), modelling the two time series as a unique multiplex network system (Lacasa et al., Sci Rep 5:15508-15508, 2014). Methods and data We used a complex network approach based on visibility graphs (Lacasa et al., Sci Rep 5:15508-15508, 2014) to model and study the behaviour of our system and to investigate how and if network topological measures can give information on the possible detection of crosstalks events taking place in the system. Each time series was converted as a layer in a multiplex network. We therefore studied the network structure, focusing on the behaviour of the two time series in the cross-talks events windows detected. We used a dataset of 27 TBI pediatric patients, admitted to Addenbrooke’s Hospital, Cambridge, Pediatric Intensive Care Unit (PICU) between August 2012 and December 2014. Results Following a preliminary statistical exploration of the two time series of ICP and HR, we analysed the multiplex network proposed, focusing on two standard topological network metrics: the mutual interaction, and the average edge overlap (Lacasa et al., Sci Rep 5:15508-15508, 2014). We compared results obtained for these two indicators, considering windows in which a cross talks event between HR and ICP was detected with windows in which cross talks events were not present. The analysis of such metrics gave us interesting insights on the time series behaviour. More specifically we observed an increase in the value of the mutual interaction in the case of cross talk as compared to non cross talk. This seems to suggest that mutual interaction could be a potentially interesting “marker” for cross talks events.