Electrophysiological Brain Monitoring after Cardiac Arrest with Temperature Management

Cardiac arrest (CA) is the leading cause of disability and death annually in the United States. Therapeutic hypothermia (TH) has been recommended as one of the standard practices for improving neurological outcome and survival to treat out-of-hospital CA patients after resuscitation. However, many clinical prognostic markers after resuscitation for predicting outcome have been less reliable under hypothermia. Therefore, there is a strong need to evaluate the prognostic value of current prognostic markers for hypoxic-ischemic brain injury after CA. The first part of this work was to review current literature and assess the prognostic value of current significant breakthroughs in neurophysiologic and electrophysiological methods for CA patients treated with TH in order to provide a comprehensive frame for future work. Due to the restrictions of standard clinical examinations and neuroimaging techniques in detecting brain injury, electroencephalography (EEG) has emerged as one of the commonly used bed-side real-time monitoring tools for prognostication. Instead of the subjective and impractical analysis of waveform-based raw EEG signals, we applied two quantitative methods – information quantity (IQ) and sub-band IQ (SIQ) – to quantify and examine the accuracy of prognostic value of EEG markers on predicting recovery under TH in the second part of this work. Our study discovered that both IQ and SIQ accurately predict neurologic outcome at the early stage of cerebral recovery. Moreover, high-frequency oscillations (HFO) were particularly noticeable during the recovery from severe brain injury indicated by IQ, and SIQ was able to provide additional standard clinical EEG bands of interests. The ischemic brain after CA is sensitive to trivial fluctuations of temperature. Previously, we only observed temperature management strongly affects the recovery of global EEG. However, EEG signals can be decomposed into different frequency sub-bands in clinical practices, which are related to different brain functions, and the association has not been elucidated between the recovery of each sub-band EEG and temperature management. In the third part of this work, we employed SIQ, of which indicative ability has been proven in the last part, to determine the most relevant sub-bands of EEG during brain recovery with temperature manipulation. It was found for the first time that gamma-band EEG activity, linked with high cognitive processes, was primarily affected by temperature and strongly associated with neurologic outcome, while delta-band played a role as constant component of EEG without stable relationship with temperature or outcome. Somatosensory evoked potentials (SSEPs), especially N20 responses in human, are able to evaluate the somatosensory system functioning, which are also regarded as a reliable early prognostic marker for post-CA neurologic outcome. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate the cerebral excitability and activity which has been confirmed by motor evoked potentials (MEPs), but it is still unclear whether it can affect the somatosensory cortex. The final part of this work preliminarily studied the alternations of excitability of somatosensory cortex by tDCS and investigated the potential of SSEPs on measuring the after-effect of tDCS

Optimizing Circadian Rhythm and Characterizing Brain Function in Disorders of Consciousness

Sleep is a physiological state where memory processing, learning and brain plasticity occur. Patients with prolonged disorders of consciousness (PDOC) show no or minimal signs of awareness of themselves or their environment but appear to have sleep-wake cycles. The main aim of this thesis was to investigate effect of circadian rhythm and sleep optimization on brain functions of patients with PDOC. In the first instance, sleep and circadian rhythms of patients with PDOC were investigated using polysomnography and saliva melatonin measurements. The investigations that were performed at the baseline suggested that both circadian rhythmicity and sleep were severely deranged in PDOC patients. This was followed by the interventional stage of the research where an attempt was made to optimize circadian rhythm and sleep by giving blue light, caffeine and melatonin in a small cohort of patients. To measure the effects of the intervention, we used a variety of assessments: Coma Recovery Scale-Revised (CRS-R) to measure changes in awareness; PSG for assessment of sleep, melatonin for assessment of circadian rhythm; and, event-related potential measures including mismatch negativity (MMN) and subject’s own name (SON) paradigms. Our results showed that it is possible to improve sleep and circadian rhythms of patients with PDOC, and most importantly, this improvement leads to increase in Coma Recovery Scale-Revised scores. Individually, those patients who responded well to the intervention also showed improvements in their functional brain imaging assessments

Therapeutic Hypothermia in Brain Injury

This book describes the evidence behind the application of Therapeutic Hypothermia on patients with injury to the brain and spinal cord, that includes ischemia reperfusion after cardiac arrest or asphyxiation, traumatic brain injury, acute ischemic stroke, hemorrhagic stroke, refractory intracranial hypertension, cerebral edema in acute liver failure, subarachnoid hemorrhage, as well as spinal cord injury. This book discusses the mechanisms by which therapeutic hypothermia can mitigate the pathophysiologies responsible for secondary brain injury, and provides information to help guide this treatment with regard to timing, depth, duration, and management of side-effects. The book also discusses the methods and technologies used to induce and maintain therapeutic hypothermia. It also describes how hypothermia can influence the ability to prognosticate these injured patients and provides grounds for future directions in the application of and research with therapeutic hypothermia

Brain Injury

The present two volume book "Brain Injury" is distinctive in its presentation and includes a wealth of updated information on many aspects in the field of brain injury. The Book is devoted to the pathogenesis of brain injury, concepts in cerebral blood flow and metabolism, investigative approaches and monitoring of brain injured, different protective mechanisms and recovery and management approach to these individuals, functional and endocrine aspects of brain injuries, approaches to rehabilitation of brain injured and preventive aspects of traumatic brain injuries. The collective contribution from experts in brain injury research area would be successfully conveyed to the readers and readers will find this book to be a valuable guide to further develop their understanding about brain injury

Biochemical and electrophysiological markers predictive of return of spontaneous circulation and post-resuscitation outcome

The majority of patients resuscitated from cardiac arrest (CA) subsequently die due to post-cardiac arrest syndrome (PCAS), whose mechanisms are only partially understood. We adopted an approach of untargeted/targeted plasma metabolomics in rats to identify metabolites involved in the mechanisms of PCAS to be tested as predictors of outcome. Activation of the kynurenine pathway (KP) for tryptophan (TRP) degradation was demonstrated in rats, pigs and in a small cohort of patients. Decreases in TRP occurred during the post-CA period and were accompanied by significant increases in KP metabolites, 3-hydroxyanthranilic acid (3 -HAA) and kynurenic acid in each species, that persisted up to 3-5 days post-CA (p<0.01). KP metabolites changes were significantly related to the severity of myocardial and cerebral injuries and survival. Finally, when tested in 155 patients resuscitated from CA, KP metabolites were significantly higher in patients with poor outcomes. The quality of chest compression (CC) is another major issue for cardiopulmonary resuscitation (CPR) success and survival. The decision whether to interrupt CC to deliver a defibrillation (DF) is difficult. The potential benefit of a DF guided by a real time ventricular fibrillation (YF) waveform analysis would maximize DF success, minimize CC interruptions and myocardial damage by repetitive and unnecessary DFs. We evaluated amplitude spectrum area (AMSA) as predictor of DF outcome in two large databases of out-of-hospital VFs, from US (609 patients) and Italy (1.617 patients). AMSA was significantly higher prior to a successful DF than prior to an unsuccessful one (p<0.0001). Thresholds for prediction of successful and unsuccessful DFs were 16-17 mV-Hz for success and <7 mV-Hz for failure, with a positive predictive value of 80% and a negative predictive value of 97%. AMSA was a better predictor of DF outcome (AUC 0.86, p<0.0001) compared to other VF parameters, i.e. amplitude and frequencies. In conclusion, AMSA would be a useful tool for guiding CPR

Project Retrosight. Understanding the returns from cardiovascular and stroke research: Case Studies

Copyright @ 2011 RAND Europe. All rights reserved. The full text article is available via the link below.This project explores the impacts arising from cardiovascular and stroke research funded 15-20 years ago and attempts to draw out aspects of the research, researcher or environment that are associated with high or low impact. The project is a case study-based review of 29 cardiovascular and stroke research grants, funded in Australia, Canada and UK between 1989 and 1993. The case studies focused on the individual grants but considered the development of the investigators and ideas involved in the research projects from initiation to the present day. Grants were selected through a stratified random selection approach that aimed to include both high- and low-impact grants. The key messages are as follows: 1) The cases reveal that a large and diverse range of impacts arose from the 29 grants studied. 2) There are variations between the impacts derived from basic biomedical and clinical research. 3) There is no correlation between knowledge production and wider impacts 4) The majority of economic impacts identified come from a minority of projects. 5) We identified factors that appear to be associated with high and low impact. This report presents the key observations of the study and an overview of the methods involved. It has been written for funders of biomedical and health research and health services, health researchers, and policy makers in those fields. It will also be of interest to those involved in research and impact evaluation.This study was initiated with internal funding from RAND Europe and HERG, with continuing funding from the UK National Institute for Health Research, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the National Heart Foundation of Australia. The UK Stroke Association and the British Heart Foundation provided support in kind through access to their archives