Blood markers for the diagnosis and prognosis of stroke William Nichol Whiteley PhD by Research University of Edinburgh 2010 Whiteley W.N . Blood Markers in Stroke University of Edinburgh 2010 Table of contents Table of contents ................................................................................................................... 2 Table of tables........................................................................................................................ 7 Table of figures.................................................................................................................... 11 Abstract................................................................................................................................. 14 Declaration........................................................................................................................... 17 Publications and awards relating to the work of this thesis......................................... 18 Abbreviations ...................................................................................................................... 21 Acknowledgments and my contribution to the work of the thesis ............................. 24 Chapter 1. Introduction ............................................................................................... 26 The importance of diagnosis and prognosis ............................................................... 26 Aims of the thesis............................................................................................................ 26 Stroke and population health........................................................................................ 27 The definition of stroke .................................................................................................. 27 Stroke subtypes ............................................................................................................... 28 The clinical diagnosis of stroke ..................................................................................... 29 Difficulties of acute imaging.......................................................................................... 33 Potential advantages of blood markers for stroke diagnosis.................................... 35 Predicting outcome after stroke.................................................................................... 37 Blood markers in improving prediction of stroke outcome...................................... 39 2 Whiteley W.N . Blood Markers in Stroke University of Edinburgh 2010 Chapter 2. Blood markers in the diagnosis of ischaemic stroke: a systematic review ................................................................................................................. 40 Introduction ..................................................................................................................... 40 Methods............................................................................................................................ 41 Results............................................................................................................................... 43 Discussion ........................................................................................................................ 46 Tables................................................................................................................................ 52 Figures .............................................................................................................................. 60 Chapter 3. Validation of clinical scores for the diagnosis of stroke and transient ischaemic attack: BBISS, a prospective cohort study ..................................................... 63 Introduction ..................................................................................................................... 63 Methods............................................................................................................................ 64 Results............................................................................................................................... 78 Discussion ........................................................................................................................ 82 Tables................................................................................................................................ 87 Figures ............................................................................................................................ 102 Chapter 4. Blood markers of inflammation, thrombosis, thrombolysis, cardiac strain, neural and glial damage and the diagnosis of acute cerebrovascular diseases in an emergency department: BBISS, a prospective cohort study ............................. 107 Introduction ................................................................................................................... 107 Methods.......................................................................................................................... 109 Results............................................................................................................................. 121 Discussion ...................................................................................................................... 127 3 Whiteley W.N . Blood Markers in Stroke University of Edinburgh 2010 Chapter 5. Blood markers for the prognosis of ischaemic stroke: a systematic review 146 Introduction ................................................................................................................... 146 Methods.......................................................................................................................... 146 Results............................................................................................................................. 148 Discussion ...................................................................................................................... 150 Conclusions.................................................................................................................... 155 Tables.............................................................................................................................. 157 Figures ............................................................................................................................ 159 Chapter 6. Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin 6................................................... 164 Introduction ................................................................................................................... 164 Methods.......................................................................................................................... 165 Results............................................................................................................................. 170 Discussion ...................................................................................................................... 173 Tables.............................................................................................................................. 178 Figures ............................................................................................................................ 184 Chapter 7. Plasma and serum markers of inflammation, thrombolysis, thrombosis, cardiac strain, neural and glial damage and poor outcome after acute cerebrovascular disease: BBISS, a prospective cohort study ...................................... 188 Introduction ................................................................................................................... 188 Methods.......................................................................................................................... 189 Results............................................................................................................................. 196 Discussion ...................................................................................................................... 201 4 Whiteley W.N . Blood Markers in Stroke University of Edinburgh 2010 Tables.............................................................................................................................. 207 Figures ............................................................................................................................ 225 Chapter 8. The association of circulating inflammatory markers with recurrent vascular events after stroke: ESS, a prospective cohort study.................................... 233 Introduction ................................................................................................................... 233 Methods.......................................................................................................................... 234 Results............................................................................................................................. 237 Discussion ...................................................................................................................... 241 Conclusion ..................................................................................................................... 244 Tables.............................................................................................................................