Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates

Abstract: Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication.For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury.Continuous multimodal monitoring as well as monitoring of sleep, sleep–wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care

Continuous quantitative monitoring of cerebral oxygen metabolism in neonates by ventilator-gated analysis of NIRS recordings

Oxidative stress during fetal development, delivery, or early postnatal life is a major cause of neuropathology, as both hypoxic and hyperoxic insults can significantly damage the developing brain. Despite the obvious need for reliable cerebral oxygenation monitoring, no technology currently exists to monitor cerebral oxygen metabolism continuously and noninvasively in infants at high risk for developing brain injury. Consequently, a rational approach to titrating oxygen supply to cerebral oxygen demand – and thus avoiding hyperoxic or hypoxic insults – is currently lacking. We present a promising method to close this crucial technology gap in the important case of neonates on conventional ventilators. By using cerebral near-infrared spectroscopy and signals from conventional ventilators, along with arterial oxygen saturation, we derive continuous (breath-by-breath) estimates of cerebral venous oxygen saturation, cerebral oxygen extraction fraction, cerebral blood flow, and cerebral metabolic rate of oxygen. The resultant estimates compare very favorably to previously reported data obtained by non-continuous and invasive means from preterm infants in neonatal critical care.National Institutes of Health (U.S.) (Grant R01EB001659)National Institutes of Health (U.S.) (Grant K24NS057568)National Institutes of Health (U.S.) (Grant R21HD056009

The Potential Role of fNIRS in Evaluating Levels of Consciousness

Over the last few decades, neuroimaging techniques have transformed our understanding of the brain and the effect of neurological conditions on brain function. More recently, light-based modalities such as functional near-infrared spectroscopy have gained popularity as tools to study brain function at the bedside. A recent application is to assess residual awareness in patients with disorders of consciousness, as some patients retain awareness albeit lacking all behavioural response to commands. Functional near-infrared spectroscopy can play a vital role in identifying these patients by assessing command-driven brain activity. The goal of this review is to summarise the studies reported on this topic, to discuss the technical and ethical challenges of working with patients with disorders of consciousness, and to outline promising future directions in this field

Spectroscopic detection of pathological severity in Alzheimer's disease

Alzheimer’s disease (AD) has emerged as one of the most widespread and devastating forms of dementia. Over the past few decades, AD has consistently increased in prevalence worldwide due to the rising proportion of elderly individuals and lack of effective screening and treatment modalities. To date, few economically viable and widely applicable tools exist to make definitive, early diagnoses of the disease. Therefore, there is a clear need for interventions that facilitate accurate diagnoses, monitoring, and therapeutic treatment of AD. In the course of AD, cognitive impairment is preceded by physiological changes to the central nervous system (CNS). This includes neuronal atrophy, synaptic dysfunction, and the abnormal post-translational modification of the proteins tau and beta-amyloid (A), which contributes to the deposition of intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs). The pathological cellular changes in AD occur long before the clinical course of the disease, and biomarkers for these changes can be detected prior to measurable cognitive decline. Because the biochemical changes associated with AD are irreversible, effective tools for diagnosis must detect the presence and severity of molecular pathology during the preliminary stages of the disease’s insidious onset. Biomarkers of AD can be detected by neuroimaging technologies, including magnetic resonance imaging (MRI), positron emission tomography (PET), and blood or cerebrospinal fluid (CSF) analyses. However, these methods are not currently suited to diagnose and monitor the unique pathogenesis of AD prior to cognitive decline. An ideal instrument for widespread AD screening, diagnosis, and monitoring must be noninvasive, inexpensive, portable, and accommodating to the cognitive sensitivities of patients on a spectrum from mild cognitive impairment (MCI) to full-blown dementia. Recently, several spectroscopic methods of assessing AD pathology have met these criteria and may be better suited for widespread clinical application. The objective of this thesis is to evaluate the use of near-infrared optical spectroscopy (NIRS) to detect pathological severity in human AD. Near-infrared (NIR) light is poorly absorbed by biological tissue, and can safely penetrate bone, skin, vasculature, and neuronal tissue. NIRS has traditionally been used in biomedical contexts to evaluate cerebral oxygenation changes, however the dense protein aggregates NFTs and NPs in AD tissue have recently been shown to characteristically affect several optical parameters of a NIR signal, including fluorescence and particle path (scattering). To date, applications of NIRS have been used to differentiate AD brains from non-AD controls in vitro, and further identify MCI patients in vivo, suggesting the NIR signal can identify molecular changes in AD. Severe AD cases are characterized by increased involvement of NFTs and NPs in the cerebral cortex, which would be expected to further affect the extent of NIR scatter. The current study aims to quantify AD-related pathology for investigation into whether the extent of optical scattering is correlated with the severity of amyloid plaque load and NFT density in the temporal cortex. Quantification of these lesions was accomplished using immunohistochemistry (IHC) and stereological analyses. Preliminary results show that the severity of AD pathology detected via IHC can be correlated with measured parameters of an in vitro near-infrared signal. Future studies aim to further characterize the relationship between scattering intensity and pathological severity, as well as evaluate the in vivo potential of this technology in predicting the clinical outcome and cognitive status of individuals in different stages of AD

Combining brain-computer interfaces and assistive technologies: state-of-the-art and challenges

In recent years, new research has brought the field of EEG-based Brain-Computer Interfacing (BCI) out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT). In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely,“Communication and Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI) to improve BCI usability, and the development of novel BCI technology including better EEG devices

Noninvasive monitoring intracranial pressure - A review of available modalities

Background: Intracranial pressure (ICP) monitoring is important in many neurosurgical and neurological patients. The gold standard for monitoring ICP, however, is via an invasive procedure resulting in the placement of an intraventricular catheter, which is associated with many risks. Several noninvasive ICP monitoring techniques have been examined with the hope to replace the invasive techniques. The goal of this paper is to provide an overview of all modalities that have been used for noninvasive ICP monitoring to date.Methods: A thorough literature search was conducted on PubMed, selected articles were reviewed in completion, and pertinent data was included in the review.Results: A total of 94 publications were reviewed, and we found that over the past few decades clinicians have attempted to use a number of modalities to monitor ICP noninvasively.Conclusion: Although the intraventricular catheter remains the gold standard for monitoring ICP, several noninvasive modalities that can be used in settings when invasive monitoring is not possible are also available. In our opinion, measurement of optic nerve sheath diameter and pupillometry are the two modalities which may prove to be valid options for centers not performing invasive ICP monitoring

Regulation of the cerebral circulation: bedside assessment and clinical implications

The regulation of the cerebral circulation relies on the complex interplay between cardiovascular, respiratory, and neural physiology. In health, these physiologic systems act to maintain an adequate cerebral blood flow (CBF) through modulation of hydrodynamic parameters; the resistance of cerebral vessels, and the arterial, intracranial, and venous pressures. In critical illness, however, one or more of these parameters can be compromised raising the possibility of disturbed CBF regulation and its pathophysiologic sequelae. The rigorous assessment of the cerebral circulation requires not only measuring CBF and its hydrodynamic determinants but also assessing the stability of CBF in response to changes in arterial pressure (cerebral autoregulation), the reactivity of CBF to a vasodilator (CO₂ reactivity for example), and the dynamic regulation of arterial pressure (baroreceptor sensitivity). Ideally, cerebral circulation monitors in critical care should be continuous, physically robust, allow for both regional and global CBF assessment, and be conducive to application at the bedside. The regulation of the cerebral circulation is impaired not only in primary neurologic conditions that affect the vasculature such as subarachnoid haemorrhage and stroke, but also in conditions that affect the regulation of intracranial pressure (such as traumatic brain injury and hydrocephalus) or arterial blood pressure (sepsis, or cardiac dysfunction). Importantly, this impairment is often associated with poor patient outcome. At present, the assessment of the cerebral circulation is primarily used as a research tool to elucidate pathophysiology or prognosis. However, when combined with other physiologic signals and online analytical techniques, cerebral circulation monitoring has the appealing potential to not only prognosticate patients, but also direct critical care management.JD is supported by a Woolf Fisher scholarship (NZ). MC is partially supported by the NIHR

Cerebral Oximetry in General Anaesthesia

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Cerebral Autoregulation-Based Blood Pressure Management In The Neuroscience Intensive Care Unit: Towards Individualizing Care In Ischemic Stroke And Subarachnoid Hemorrhage

The purpose of this thesis is to review the concept of cerebral autoregulation, to establish the feasibility of continuous bedside monitoring of autoregulation, and to examine the impact of impaired autoregulation on functional and clinical outcomes following subarachnoid hemorrhage and ischemic stroke. Autoregulation plays a key role in the regulation of brain blood flow and has been shown to fail in acute brain injury. Disturbed autoregulation may lead to secondary brain injury as well as worse outcomes. Furthermore, there exist several methodologies, both invasive and non-invasive, for the continuous assessment of autoregulation in individual patients. Resultant autoregulatory parameters of brain blood flow can be harnessed to derive optimal cerebral perfusion pressures, which may be targeted to achieve better outcomes. Multiple studies in adults and several in children have highlighted the feasibility of individualizing mean arterial pressure in this fashion. The thesis herein argues for the high degree of translatability of this personalized approach within the neuroscience intensive care unit, while underscoring the clinical import of autoregulation monitoring in critical care patients. In particular, this document recapitulates findings from two separate, prospectively enrolled patient groups with subarachnoid hemorrhage and ischemic stroke, elucidating how deviation from dynamic and personalized blood pressure targets associates with worse outcome in each cohort. While definitive clinical benefits remain elusive (pending randomized controlled trials), autoregulation-guided blood pressure parameters wield great potential for constructing an ideal physiologic environment for the injured brain. The first portion of this thesis discusses basic autoregulatory physiology as well as various tools to interrogate the brain’s pressure reactivity at the bedside. It then reviews the development of the optimal cerebral perfusion pressure as a biological hemodynamic construct. The second chapter pertains to the clinical applications of bedside neuromonitoring in patients with aneurysmal subarachnoid hemorrhage. In this section, the personalized approach to blood pressure monitoring is discussed in greater detail. Finally, in the third chapter, a similar autoregulation-oriented blood pressure algorithm is applied to a larger cohort of patients with ischemic stroke. This section contends that our novel, individualized strategy to hemodynamic management in stroke patients represents a better alternative to the currently endorsed practice of maintaining systolic blood pressures below fixed and static thresholds