Metabolic biomarker responses in acute cerebral events
File(s)
Author(s)
Coupland, Alexander P
Type
Thesis
Abstract
Aims
The aims of this study were to identify a potential blood biomarker for acute stroke and additionally to identify biomarkers capable of differentiating hyper-acute ischaemic from haemorrhagic stroke using metabonomic techniques.
Methodology
Following ethical approval participants were recruited from the hyper-acute stroke unit at Charing Cross Hospital and acute blood samples taken from patients who were suspected of having an acute stroke. Serum was extracted and frozen prior to MS and NMR analysis. Sub-acute TIA patients were used as a comparative group and patients with known atherosclerotic disease as a non-acute control group. A total of 90 participants were recruited for analysis.
Positive and negative mode reverse phase UPLC-MS and additionally 1H-NMR spectroscopy were used to analyse prepared serum samples. Modelling was performed using OPLS-DA and CA-PLS techniques where appropriate following permutation analysis to detect discriminatory metabolites between participant groups.
Results
Positive mode mass spectrometry detected metabolites that could differentiate between participants who had suffered an acute cerebral ischaemic event (inclusive of stroke and acute TIA) and those participants that were known to have established atherosclerotic disease. The metabolites detected include phosphatidylcholines, sphingomyelins and a ganglioside. Unfortunately, due to a relatively small sample size the CA-PLS false discovery rate analysis found the initial results to lack statistical significance (Q value = 0.95). It was not possible to metabolically differentiate between acute ischaemic and haemorrhagic strokes.
Conclusion
Despite the relatively small sample size leading to a confirmed false discovery rate analysis the initial findings of elevated phosphatidylcholines, sphingomyelins and the peripheral detection of a ganglioside in relation to acute cerebral ischaemia is promising and follows a trend in the published literature. Further studies with a larger sample size, rigorous follow up and temporal trend analysis using dedicated lipidomic techniques may find a sensitive diagnostic serological biomarker for hyper-acute stroke and transient ischaemic attack.
The aims of this study were to identify a potential blood biomarker for acute stroke and additionally to identify biomarkers capable of differentiating hyper-acute ischaemic from haemorrhagic stroke using metabonomic techniques.
Methodology
Following ethical approval participants were recruited from the hyper-acute stroke unit at Charing Cross Hospital and acute blood samples taken from patients who were suspected of having an acute stroke. Serum was extracted and frozen prior to MS and NMR analysis. Sub-acute TIA patients were used as a comparative group and patients with known atherosclerotic disease as a non-acute control group. A total of 90 participants were recruited for analysis.
Positive and negative mode reverse phase UPLC-MS and additionally 1H-NMR spectroscopy were used to analyse prepared serum samples. Modelling was performed using OPLS-DA and CA-PLS techniques where appropriate following permutation analysis to detect discriminatory metabolites between participant groups.
Results
Positive mode mass spectrometry detected metabolites that could differentiate between participants who had suffered an acute cerebral ischaemic event (inclusive of stroke and acute TIA) and those participants that were known to have established atherosclerotic disease. The metabolites detected include phosphatidylcholines, sphingomyelins and a ganglioside. Unfortunately, due to a relatively small sample size the CA-PLS false discovery rate analysis found the initial results to lack statistical significance (Q value = 0.95). It was not possible to metabolically differentiate between acute ischaemic and haemorrhagic strokes.
Conclusion
Despite the relatively small sample size leading to a confirmed false discovery rate analysis the initial findings of elevated phosphatidylcholines, sphingomyelins and the peripheral detection of a ganglioside in relation to acute cerebral ischaemia is promising and follows a trend in the published literature. Further studies with a larger sample size, rigorous follow up and temporal trend analysis using dedicated lipidomic techniques may find a sensitive diagnostic serological biomarker for hyper-acute stroke and transient ischaemic attack.
Version
Open Access
Date Issued
2020-12
Date Awarded
2021-06
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
License URL
Advisor
Davies, Alun
Thapar, Ankur
Holmes, Elaine
Sponsor
Imperial Private Healthcare
Graham Dixon Charitable Trust
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)