Cerebral Microbleeds as a Marker of Small Vessel Disease: New Insights from Neuro-imaging and Clinical Studies in Stroke Patients

....................................................................................................................................... 5 LIST OF PUBLICATIONS ..................................................................................................................... 6 TABLE OF CONTENTS........................................................................................................................ 8 LIST OF FIGURES ................................................................................................................................13 LIST OF TABLES ..................................................................................................................................16 ABBREVIATIONS............................................................................................................................. 18 PREFACE......................................................................................................................................... 20 PART 1: INTRODUCTION TO SMALL VESSEL DISEASE AND CEREBRAL MICROBLEEDS...................... 21 CHAPTER 1 SMALL VESSEL DISEASE: DEFINITION AND CLINICAL RELEVANCE................................ 21 1.1 SMALL VESSEL DISEASE: DEFINITIONS AND CLASSIFICATION........................................................................22 1.2 HISTORICAL BACKGROUND .................................................................................................................25 1.2.1 History of lacunes and white matter lesions....................................................................... 25 1.2.2 History of cerebral amyloid angiopathy ............................................................................. 27 1.3 PATHOLOGICAL FEATURES ..................................................................................................................30 1.3.1 Age-related and hypertension-related small vessel arteriopathy ...................................... 30 1.3.2 Cerebral amyloid angiopathy ............................................................................................. 33 1.4 IMAGING SPECTRUM OF SMALL VESSEL DISEASE ......................................................................................39 1.4.1 Recent small subcortical infarcts ........................................................................................ 40 1.4.2 Lacune of presumed vascular origin ................................................................................... 41 1.4.3 White matter hyperintensity of presumed vascular origin................................................. 42 1.4.4 Perivascular space .............................................................................................................. 46 1.4.5 Cerebral microbleeds .......................................................................................................... 47 1.4.6 Brain atrophy...................................................................................................................... 48 1.4.7 Other haemorrhagic brain lesions ...................................................................................... 49 1.5 MECHANISMS OF SMALL VESSEL DISEASE...............................................................................................52 1.6 CLINICAL SPECTRUM OF CEREBRAL SMALL VESSEL DISEASE.........................................................................58 1.6.1 Ischaemic manifestations ................................................................................................... 58 1.6.2 Haemorrhagic manifestations............................................................................................ 60 1.6.3 Cerebral amyloid angiopathy ............................................................................................. 61 1.6.4 Cognitive impairment ......................................................................................................... 66 CHAPTER 2 INTRODUCTION TO CEREBRAL MICROBLEEDS............................................................ 72 2.1 FROM MICROANEURYSMS AND HAEMOSIDERIN DEPOSITS TO CEREBRAL MICROBLEEDS ...................................73 2.1.1 Charcot-Bouchard microaneurysms ................................................................................... 73 2.1.2 The first MRI reports of ‘microbleeds’ ................................................................................ 86