Publications by authors named "Sharon Jewell"

A core aim of neurocritical care is to prevent secondary brain injury. Spreading depolarizations (SDs) have been identified as an important independent cause of secondary brain injury. SDs are usually detected using invasive electrocorticography recorded at high sampling frequency.

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Background: Spreading depolarizations (SDs) occur in some 60% of patients receiving intensive care following severe traumatic brain injury and often occur at a higher incidence following serious subarachnoid hemorrhage and malignant hemisphere stroke (MHS); they are independently associated with worse clinical outcome. Detection of SDs to guide clinical management, as is now being advocated, currently requires continuous and skilled monitoring of the electrocorticogram (ECoG), frequently extending over many days.

Methods: We developed and evaluated in two clinical intensive care units (ICU) a software routine capable of detecting SDs both in real time at the bedside and retrospectively and also capable of displaying patterns of their occurrence with time.

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Current explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify to which extent a seizure is focal or generalised.

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Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics.

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We present approaches to facilitate the use of microfluidics outside of the laboratory, in our case within a clinical setting and monitoring from human subjects, where the complexity of microfluidic devices requires high skill and expertise and would otherwise limit translation. Microfluidic devices show great potential for converting complex laboratory protocols into on-chip processes. We demonstrate a flexible microfluidic platform can be coupled to microfluidic biosensors and used in conjunction with clinical microdialysis.

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This paper presents the design, optimisation and fabrication of a mechanically robust 3D printed microfluidic device for the high time resolution online analysis of biomarkers in a microdialysate stream at microlitre per minute flow rates. The device consists of a microfluidic channel with secure low volume connections that easily integrates electrochemical biosensors for biomarkers such as glutamate, glucose and lactate. The optimisation process of the microfluidic channel fabrication, including for different types of 3D printer, is explained and the resulting improvement in sensor response time is quantified.

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Spreading depolarizations occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an spreading depolarization requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential.

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Epilepsy is one of the most common serious neurologic conditions. It is characterized by the tendency to have recurrent seizures, which arise against a backdrop of apparently normal brain activity. At present, clinical diagnosis relies on the following: (1) case history, which can be unreliable; (2) observation of transient abnormal activity during electroencephalography (EEG), which may not be present during clinical evaluation; and (3) if diagnostic uncertainty occurs, undertaking prolonged monitoring in an attempt to observe EEG abnormalities, which is costly.

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Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes.

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Background: Spreading depolarization events following ischemic and traumatic brain injury are associated with poor patient outcome. Currently, monitoring these events is limited to patients in whom subdural electrodes can be placed at open craniotomy. This study examined whether these events can be detected using intra-cortical electrodes, opening the way for electrode insertion via burr hole.

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Background: Refractory status epilepticus (RSE) is associated with high mortality. We report a potential treatment alternative.

Hypothesis: Deep brain stimulation (DBS) of the centromedian thalamic nuclei (CMN) can be effective in the treatment of RSE.

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The symmetry of the cholesteric uniform lying helix (ULH) structure, where the helix axis is aligned in a single direction parallel to the device substrates, is not compatible with a uniform surface alignment and an unwinding of the helical structure is expected at the interface. Fluorescence confocal polarizing microscopy experiments are performed on the interface between a bulk ULH and a uniform aligning surface (for both planar and homeotropic alignments). The results are analyzed in the framework of a finite difference numerical simulation based on the Frank elastic distortion, to determine relevant director structures.

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