- Title
- Exploration and application of biochemical markers to aid diagnosis of central nervous system infections
- Creator
- Zhang, Michael
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Introduction: This thesis examines the diagnostic performance of a variety of clinical, serum and CSF markers to predict CNS infections. Many general inflammatory markers have been studied fairly extensively with relation to CNS infections, but the literature on the neural specific markers in CNS infections is still limited and the results are currently far from being conclusive. This thesis aims to explore a variety of inflammatory markers to enhance our understanding of their diagnostic accuracy for CNS infections, and then apply these markers to a cohort of patients to directly compare their diagnostic performance. Methods: This thesis starts by launching a clinicians’ survey to evaluate the contemporary clinical practice patterns for managing possible CNS infections. This thesis then explores the diagnostic accuracy of a variety of clinical features, and general and neural specific markers, in the serum and in the CSF that have been published in the literature. This was accomplished by undertaking a systematic review and meta-analysis of these markers to compare their diagnostic performance for CNS infections. This thesis finally undertook a prospective study to apply multiple general and neural specific markers in the serum and in the CSF on a cohort of patients who were suspected to have CNS infections. Results: The clinician survey demonstrates the diagnostic dilemma and the issues of local clinicians managing patients with suspected CNS infections. The survey results also demonstrate the extent of evidence based medicine that influences these clinicians. The systematic review and meta-analysis of multiple makers for all types of CNS infections shows a higher diagnostic accuracy of CSF markers overall in comparison with clinical features and the serum markers. Serum PCT and serum CRP were found to be excellent general inflammatory markers to distinguish certain types of CNS infections. From this literature review, the literature on the neural specific markers that are used to predict CNS infections are still limited and inconclusive. The prospective cohort study provided further evidence on some of the neural specific markers that were used to investigate patients with possible CNS infections. The higher levels of NSE and S100B in the CSF were reflective of the pathophysiological changes in the event of CNS infection. The results of this study also suggest the impairment of the blood brain barrier in CNS infections, especially in serious infection such as bacterial meningitis and meningoencephalitis. Higher serum S100B and NSE levels in these diagnostic sub-groups is believed to be caused by efflux of S100B and NSE from the intra-thecal space of CNS to systemic circulation as a result of a leaky blood brain barrier in these conditions. Although similar changes of concentration were not evident in this study for GFAP, the serum GFAP levels were very high in deceased patients and in patients with elevated intracranial pressure. Nevertheless, the results of this study did not indicate a superior diagnostic performance for CNS infections of these neural specific markers over other markers. Conclusions: The results from this thesis highlight the challenging problem of predicting CNS infections by using individual markers. Whilst some of the neural specific biomarkers were observed to have higher levels in some patients with CNS infections than in the controls, the results of this and previous studies indicate that, given our best available evidence, the neural specific biomarkers being studied in this project, including S100B, NSE, and GFAP, do not appear to have a greater diagnostic accuracy for CNS infections than the other markers. However, a risk stratification model developed by combining S100B and meningism signs can be a helpful screening tool for the patients suspected to have CNS infections.
- Subject
- CNS infections; diagnosis; biochemical markers; clinicians; systematic review
- Identifier
- http://hdl.handle.net/1959.13/1408465
- Identifier
- uon:35842
- Rights
- Copyright 2019 Michael Zhang
- Language
- eng
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| View Details Download | ATTACHMENT01 | Thesis | 14 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 1 MB | Adobe Acrobat PDF | View Details Download |