Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance

<p>Abstract</p> <p>Background</p> <p>A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (<it>C</it>_out) or its reciprocal the outflow resistance (<it>R</it>_out), with or without using the baseline resting pressure, <it>P</it>_r. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating <it>C</it>_out using two different analyses, with or without <it>P</it>_r, the limitations could be explored. The aim of this study was to compare the <it>C</it>_out estimates, and investigate what effect <it>P</it>_rhad on the results.</p> <p>Methods</p> <p>Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3 ± 10.8 years (mean ± SD)). The analysis was performed without (<it>C</it>_{excl Pr}) and with (<it>C</it>_{incl Pr}) P_r. The estimates were compared using Bland-Altman plots and paired sample <it>t</it>-tests (<it>p </it>< 0.05 considered significant).</p> <p>Results</p> <p>Mean <it>C</it>_out for the 63 patients was: <it>C</it>_{excl Pr}= 7.0 ± 4.0 (mean ± SD) μl/(s kPa) and <it>C</it>_{incl Pr} = 9.1 ± 4.3 μl/(s kPa) and <it>R</it>_out was 19.0 ± 9.2 and 17.7 ± 11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r = 0.79, n = 63, <it>p </it>< 0.01). The difference, Δ<it>C</it>_out= -2.1 ± 2.7 μl/(s kPa) between methods was significant (<it>p </it>< 0.01) and Δ<it>R</it>_outwas 1.2 ± 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between Δ<it>C</it>_outand <it>C</it>_out.</p> <p>Conclusions</p> <p>The difference between <it>C</it>_outestimates, obtained from analyses with or without <it>P</it>_r, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent <it>C</it>_outas possible causes for the deviation from the CSF absorption model seen in some patients.</p

Clinical Applications of Neuromonitoring Following Acute Brain Injury

Various invasive and non-invasive cranial monitoring techniques can be applied clinically to describe the extent to which cerebral hemodynamics and subsequently, patient outcome, have been impacted following acute brain injury (ABI). This Ph.D. thesis examines both prospective and retrospective patient data in both neurocritical and general intensive care patients. Thirty neurotrauma patients and forty general intensive care patients with neurological complications were prospectively monitored after ABI. Retrospective patient data was harvested from a database of 1,023 traumatic brain injury (TBI) patients with invasive intracranial pressure (ICP), arterial blood pressure (ABP), and transcranial Doppler ultrasonography (TCD) recordings. Data analysis focused on ICP microsensor accuracy, compensatory reserve, the pulsatility of brain signals (ICP and TCD), and cerebral arterial blood volume (CaBV) based on TCD. The main results are summarized below: I. Intracranial hypertension has a profound negative influence on cerebrovascular parameters and patient outcome. II. ICP microsensor accuracy is limited, with an average error of approximately ± 6.0 mm Hg. III. ICP weighted with the compensatory reserve better predicts outcome than mean ICP alone. IV. ICP and TCD pulsatility are functions of mean ICP and cerebral perfusion pressure (CPP). V. Continuous blood flow forward (CFF) and pulsatile blood flow forward (PFF) models can approximate CaBV with derived TCD signals; CFF best models TCD pulsatility. VI. The pressure reactivity index (PRx) and the pulse amplitude index (PAx) can be estimated non-invasively using slow waves of TCD estimated by CaBV with similar outcome-predictive power. VII. Multi-parametric TCD-based monitoring of general intensive care patients is clinically feasible; the joint estimation of autoregulation, dysautonomia, non-invasive ICP, and critical closing pressure is possible. The culmination of these projects should have an impact on current monitoring practices in ABI patients, emphasizing the continued validation and refinement of TCD methodology in clinical neurosciences

Computational methods toward early detection of neuronal deterioration

In today's world, because of developments in medical sciences, people are living longer, particularly in the advanced countries. This increasing of the lifespan has caused the prevalence of age-related diseases like Alzheimer’s and dementia. Researches show that ion channel disruptions, especially the formation of permeable pores to cations by Aβ plaques, play an important role in the occurrence of these types of diseases. Therefore, early detection of such diseases, particularly using non-invasive tools can aid both patients and those scientists searching for a cure. To achieve the goal toward early detection, the computational analysis of ion channels, ion imbalances in the presence of Aβ pores in neurons and fault detection is done. Any disruption in the membrane of the neuron, like the formation of permeable pores to cations by Aβ plaques, causes ionic imbalance and, as a result, faults occur in the signalling of the neuron.The first part of this research concentrates on ion channels, ion imbalances and their impacts on the signalling behaviour of the neuron. This includes investigating the role of Aβ channels in the development of neurodegenerative diseases. Results revealed that these types of diseases can lead to ionic imbalances in the neuron. Ion imbalances can change the behaviour of neuronal signalling. Therefore, by identifying the pattern of these changes, the disease can be detected in the very early stages. Then the role of coupling and synchronisation effects in such diseases were studied. After that, a novel method to define minimum requirements for synchronicity between two coupled neurons is proposed. Further, a new computational model of Aβ channels is proposed and developed which mimics the behaviour of a neuron in the course of Alzheimer's disease. Finally, both fault computation and disease detection are carried out using a residual generation method, where the residuals from two observers are compared to assess their performance

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 145

This bibliography lists 301 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1975

Readings in Advanced Pharmacokinetics

This book, “Readings in Advanced Pharmacokinetics - Theory, Methods and Applications”, covers up to date information and practical topics related to the study of drug pharmacokinetics in humans and in animals. The book is designed to offer scientists, clinicians and researchers a choice to logically build their knowledge in pharmacokinetics from basic concepts to advanced applications. This book is organized into two sections. The first section discusses advanced theories that include a wide range of topics; from bioequivalence studies, pharmacogenomics in relation to pharmacokinetics, computer based simulation concepts to drug interactions of herbal medicines and veterinary pharmacokinetics. The second section advances theory to practice offering several examples of methods and applications in advanced pharmacokinetics

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 183

This bibliography lists 273 reports, articles, and other documents introduced into the NASA scientific and technical information system in July 1978

SPECTRAL DOMAIN OCT DOPPLER ASSESSES AQUEOUS OUTFLOW

Glaucoma is the second leading cause of blindness worldwide, affecting approximately 67 million people and costing the US healthcare system an estimated $2.5 billion annually. The greatest risk factor for the diagnosis and progression of glaucoma is high eye pressure. All glaucoma medications and procedures are designed to reduce eye pressure, slowing disease progression and preserving vision. The eye’s aqueous humor nourishes avascular tissues in the anterior segment. It also maintains the eye’s geometry by pressurizing the globe, facilitating its ability to focus light on the retina. The balance between aqueous humor production and uptake is responsible for the pressure within the eye. Most glaucoma medications are designed to reduce pressure by increasing aqueous humor outflow, and surgeries are designed to enhance or bypass exiting outflow pathways. But, the effects of medications and procedures on a patient by patient basis on outflow remain speculative. Here, techniques for the non-invasive direct mapping and measurement of aqueous humor outflow in the living human eye are proposed. Mapping provides morphometric insights and measurements of the components of the outflow system, while the flow technique is the first to provide direct measurements of outflow, free of the assumptions plaguing other modalities. “Virtual casting” of the outflow system yields 3D maps from which terminal branches are identified. Doppler measurements quantify velocity within those branches. Total aqueous humor outflow is determined by integrating calculated flow across all identified terminal branches. These technologies can be adapted to existing FDA approved OCT clinical scanners. Clinical application of these technologies may improve the management of glaucoma by reducing the time needed to determine and implement optimal therapeutic strategies, thereby preserving vision in glaucoma patients

Aerospace Medicine and Biology: A cumulative index to a continuing bibliography

This publication is a cumulative index to the abstracts contained in Supplements 138 through 149 of AEROSPACE MEDICINE AND BIOLOGY: A CONTINUING BIBLIOGRAPHY. It includes three indexes -- subject, personal author, and corporate source