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Cerebral Microbleeds
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Book description

Stroke is a leading cause of death and disability throughout the world. About one in three symptomatic strokes are due to disease of small perforating arteries; however, most effective interventions are targeted at disease of large arteries. The underlying mechanisms and treatment of small vessel disease remain poorly understood. Microbleeds have emerged as a critical imaging marker of small vessel disease, being found in all types of stroke. With increasing evidence that microbleeds are caused by hypertensive arteriopathy and cerebral amyloid angiopathy, they are likely to play a strong future role in increasing our understanding of the causes of small vessel disease and the potential link between cerebrovascular disease and neurodegeneration. Cerebral Microbleeds summarizes our current knowledge, bringing together expert research from global authorities in the field. This authoritative and systematic text will be of interest to all clinical researchers and physicians in the fields of stroke and cognitive impairment.

Reviews

'Cerebral Microbleeds: Pathophysiology to Clinical Practice is a 198-page textbook that covers the entire current state of knowledge on microbleeds, ranging from the historical perspective to current imaging methods and histopathology … David Werring has succeeded in assembling virtually all authorities on cerebral microbleeds to share their knowledge and views on this emerging topic. This has yielded a comprehensive overview that is of interest both to the uninitiated student wanting to know what all the fuss is about and to the more experienced neuroscientist working in the field of cerebral small vessel disease.'

Source: The Lancet

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Contents


Page 1 of 2


  • Chapter 6 - Histopathologyof cerebral microbleeds
    pp 49-64
  • View abstract

    Summary

    This chapter describes the development of knowledge concerning microaneurysmal and small hemorrhagic lesions in relation to intracerebral hemorrhage (ICH) and small vessel diseases, which may be relevant in understanding the origin of radiologically defined cerebral microbleeds (CMBs). The hypothesis that has arisen from the work of Jean-Martin Charcot and Charles-Joseph Bouchard is that pathological changes (degenerative or inflammatory, and often associated with arterial hypertension) in small caliber arterioles (up to approximately 300 µm) cause weakening of the wall and microaneurysm formation, which subsequently may rupture to cause ICH. Cerebral microbleeds are particularly common in ICH suggesting that they may provide clues to the underlying cause and could potentially shed light on the role of microaneurysms. Cerebral amyloid angiopathy is now recognized as a common disorder of elderly populations and is characterized by the deposition of amyloid in cerebral cortical and leptomeningeal small vessels.
  • Chapter 8 - Relationship of cerebral microbleeds to other imaging findings
    pp 71-78
  • View abstract

    Summary

    Of the metals that are commonly present in the human brain, it is considered that only iron in the form of ferritin and hemosiderin is present in sufficient quantities and appropriate oxidation state to be visualized by magnetic resonance imaging (MRI). Histology has shown that cerebral microbleeds (CMBs) contain hemosiderin deposits, a paramagnetic substance. In attempts to quantify the actual susceptibility distribution, many different models have been proposed, which relate measurable MRI effects to the underlying susceptibility distribution. However, for the detection of CMBs it is probably sufficient to use qualitative techniques with a high sensitivity to magnetic field inhomogeneities to provide information on the location and approximate size of the CMB. This chapter describes some possible technical developments to discriminate between some of the different origins of signal loss. The introduction of higher-field scanners and the development of new sequences can provide increased sensitivity for the detection of CMBs.
  • Chapter 9 - Cerebral microbleeds in healthypopulations
    pp 79-86
  • View abstract

    Summary

    Susceptibility-weighted imaging (SWI) has proven to be a very sensitive technique for the identification of cerebral microbleeds (CMBs). Increased sensitivity to CMBs may allow assessment of the rate of microhemorrhage development or regression, allowing more precise analysis of the natural history of disease, or better assessment of response to therapy. Early recognition may be advantageous to patients treated with anticoagulant or aspirin therapy in that they are at increased risk for subsequent and possibly fatal hemorrhage. There are in the order of 1.4 million people a year affected by traumatic brain injury (TBI). For these patients, computed tomography (CT) is the mainstay of imaging in the emergency setting and does a good job detecting major bleeds. Radiation damage to blood vessels and radiation necrosis can result from treating tumors and disease with potentially damaging doses of radiation. Future semiautomated methods hold promise for evaluating large numbers of patients using SWI.
  • Chapter 10 - Cerebral microbleeds in relation to cerebrovasculardisease
    pp 87-98
  • View abstract

    Summary

    Cerebral microbleeds (CMBs) are an increasingly common radiological finding in stroke, neurological and general medical practice. There are two published CMB rating scales that have been validated in hospital cohorts of stroke patients. The rating scales are the microbleed anatomical rating scale (MARS) and the brain observer micro bleed scale (BOMBS). This chapter considers the radiological criteria for defining CMBs and then discusses these standardized rating scales. The potential for automatically detecting and mapping CMBs in future is discussed briefly in the chapter. Mapping CMBs gives information on the burden of CMBs in different anatomical regions in the brain. Quantifying the number of CMBs may be relevant in exploring their relationship with other quantitative imaging or clinical data and for prognostic purposes. Although visual rating scales can improve the reliability of identifying and mapping CMBs, more sophisticated automated methods are under investigation.
  • Chapter 11 - Cerebral microbleeds in relation to hypertensivearteriopathy
    pp 99-108
  • View abstract

    Summary

    The cerebral microbleed (CMB) mimics form two types: those that contain blood products and those that do not (resembling CMBs because of shared signal intensity and morphology on gradient-recalled echo (GRE) MRI). This chapter describes both types, and outlines how these can be differentiated from true CMBs. It suggests a topographical approach to the recognition of CMB mimics on brain imaging. The GRE sequences used in the detection of CMBs are sensitive not only to blood breakdown products (deoxyhemoglobin, methemoglobin, hemosiderin and ferritin) but also to other paramagnetic substances such as calcium, manganese and iron, all of which may appear as foci of low signal. In lobar regions of the brain, common CMB mimics include vascular flow voids and hypointensities arising from partial volume artefact. The development of susceptibility-weighted imaging (SWI) has improved the detection of structures containing extravascular blood products, as well as those containing venous deoxygenated blood.
  • Chapter 12 - Cerebral microbleeds in relation to cerebral amyloidangiopathy
    pp 109-116
  • View abstract

    Summary

    This chapter describes the vascular pathologies that underlie cerebral microbleeds (CMBs), concentrating on the two commonest disorders: hypertensive small vessel disease (SVD) and cerebral amyloid angiopathy (CAA). It also describes the process of blood degradation, and the correlation of imaging with histological findings. The chapter concentrates on hypertensive arteriopathy and CAA, which is usually diagnosed following symptomatic lobar intracerebral hemorrhage (ICH). Hypertensive arteriopathy is thought to be caused by a forced dilation of resistance vessels: that is, those vessels that regulate the blood supply volume to the distal capillary bed. The first event in a hemorrhage is the extravasation of all constituents of blood along with plasma. Extravasation may occur by rhexis (rupture of a vessel wall) or by diapedesis affecting arterioles, veins or capillaries. From the perspective of neuroimaging, CMBs are focal deposits of hemosiderin and can be visualized with MRI.
  • Chapter 14 - Cerebral microbleeds in relation to braintrauma
    pp 125-134
  • View abstract

    Summary

    Cerebral microbleeds (CMBs) reflect an underlying angiopathy currently thought to result mainly from hypertension or from the deposition of beta-amyloid in small and micro vessel walls. This chapter describes the prevalence of, and risk factors for, CMBs and methodological issues related to their study. CMBs can be present in up to 80% of a clinical hemorrhagic stroke sample. Most studies with a reasonable distribution of subject age and sample size show CMB prevalence increases with age. There is robust evidence that high blood pressure, measured in different ways, is a risk factor for CMB. Most genetic diseases with increased susceptibility to CMBs are rare. The only candidate susceptibility gene identified as risk modifying is APOE. Research on risk factors for CMBs will bring into better focus issues related to comorbidity with other vascular and neurodegenerative lesions and location and number of lesions.
  • Chapter 15 - Cerebral microbleeds inCADASIL
    pp 135-141
  • View abstract

    Summary

    Cerebral microbleeds (CMB) are considered a marker of an underlying hemorrhage-prone small vessel vasculopathy. The brain changes that accompany CMB may be a direct consequence of the CMB, of an underlying vasculopathy, or of risk factors associated with CMB or the underlying vasculopathies that cause CMB. This chapter reviews data associating CMBs with other neuroimaging findings. The relationships between CMBs and brain infarcts, hemorrhage and brain atrophy is discussed in general and in the context of specific small vessel diseases. CMBs are more frequent in patients with neuroimaging findings of white matter lesions (WML) and lacunar infarctions. By contrast, CMBs are not independently associated with brain atrophy, probably because the actual tissue damage directly caused by CMBs is minimal. These observations are consistent with the concept that CMBs are one of several neuroimaging markers of small vessel arterial disease.
  • Chapter 16 - Miscellaneous conditions associated with cerebralmicrobleeds
    pp 142-151
  • View abstract

    Summary

    This chapter summarizes the current knowledge on prevalence and characteristics of cerebral microbleeds (CMBs) in normal individuals. The most solid knowledge on CMBs comes from the population-based studies, in particular those that have included higher age groups and have used a sensitive technique to detect CMBs. The four population-based studies with reported findings on CMBs in normal individuals are the Austrian Stroke Prevention Study, the Framingham Study, the Age Gene/Environment Susceptibility (AGES)-Reykjavik study (AGES-R) and the Rotterdam Scan Study. A pioneering study from Japan studied the prevalence of CMBs in 450 neurologically healthy Japanese adults with a mean age of 52.9 years. The overall incidence was 3.1% (14/450), and lesions detected were closely related to hypertension and heavy cigarette smoking. Patterns of risk factors and comorbidities are different between regions, and one can assume that such factors should also affect prevalence rates of CMBs.
  • Chapter 18 - Other clinical manifestations of cerebralmicrobleeds
    pp 159-164
  • View abstract

    Summary

    This chapter provides an overview of the prevalence and associations, temporal evolution and prognostic significance of cerebral microbleeds (CMBs) in patients with cerebrovascular diseases. The spatial distribution of microbleeds, as markers of small vessel microhemorrhagic or microaneurysmal lesions, may be of particular interest in attempts to understand the causes of macroscopic intracerebral hemorrhage (ICH) in life. Cerebral amyloid angiopathy is an important cause of primary ICH, particularly of lobar location. Chronic hypertension has been repeatedly identified as a strong influence on the frequency and extent of CMBs, in patients with established stroke as well as in healthy subjects without stroke. Hypertension is an important risk factor for CMBs. As CMBs reflect the bleeding tendency of the brain through fragile microvascular walls, interest has increased in utilizing CMBs in risk stratification of hemorrhagic complications for patients with antithrombotic treatment.
  • Chapter 19 - Cerebral microbleeds and antithrombotictreatment
    pp 165-172
  • View abstract

    Summary

    This chapter reviews the pathophsyiology and pathology of hypertensive arteriopathy of the brain and its relationship to neuroimaging findings, particularly cerebral microbleeds (CMBs). The prevalence of hypertension is highly age dependent. Hypertension-related cerebral diseases include hypertensive encephalopathy, stroke and vascular cognitive impairment. Although the term arteriopathy includes both arteries and arterioles, the chapter focuses on the intrinsic vascular pathology of arterioles in hypertension. Intracranial atherosclerosis of large arteries is more common in hypertension. The presence of hypertensive arteriolosclerosis must be inferred indirectly. Hypertension is a common age-related disease that is accompanied by loss of vascular integrity, with leakage of red blood cells and perivascular hemosiderin deposition. Cerebral microbleeds caused by hypertensive arteriopathy may be seen in the deep hemispheric regions, brainstem, cerebellum and cerebral lobes; however, the pattern of purely lobar CMBs strongly suggests cerebral amyloid angiopathy (CAA) rather than hypertensive arteriopathy.

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