Cerebral microbleeds: a new dilemma in stroke medicine

摘要

Cerebral microbleeds (CMBs) are an increasingly common neuroimaging finding in the context of ageing, cerebrovascular disease and dementia, with potentially important clinical relevance. Perhaps the most pressing clinical question is whether CMBs are associated with a clinically important increase in the risk of intracerebral haemorrhage (ICH), the most feared complication in patients treated with thrombolytic or antithrombotic (antiplatelet and anticoagulant) drugs. This review will summarize the evidence available regarding CMBs as an indicator of future ICH risk in stroke medicine clinical practice. Previous SectionNext Section Introduction In the mid-1990s reports began to appear of small haemorrhagic lesions on magnetic resonance imaging (MRI) studies. Scharf et al.1 described black dots of signal loss on T2-weighted MRI in patients with spontaneous intracerebral haemorrhage (ICH) and termed these ‘haemorrhagic lacunes’. Subsequent studies using T2*-weighted gradient-echo (T2*-GRE) MRI – a technique with greater sensitivity to the signal loss from magnetic ‘susceptibility’ effects of blood breakdown products – detected small round black dots which have become known as ‘cerebral microbleeds’ (CMBs).2 Because CMBs reflect small areas of haemorrhage, and are common in both ischaemic stroke and ICH,3 they have caused concern regarding the risk of future ICH, especially in patients receiving antithrombotic therapy. Although randomized controlled prospective data are lacking, observational data suggest that CMBs are indeed related to an increased future stroke risk, particularly for ICH. Here, we review the available evidence with reference to common clinical scenarios including those where the optimum management may be uncertain. Previous SectionNext Section Pathology, detection and definition of CMBs Before considering their clinical significance, it is necessary to briefly discuss aspects of CMB pathology, detection and classification. CMBs are small perivascular haemosiderin-deposits (usually within macrophages) in the brain, generally associated with local vessel wall damage.4 Histopathological analyses of the brains of patients with spontaneous ICH or Alzheimer's disease have shown that CMBs are located in proximity to vessels affected by two types of sporadic small vessel disease: (a) hypertensive arteriopathy and (b) cerebral amyloid angiopathy (CAA).5 CMBs are found throughout the brain, including cortical grey and white matter, the basal ganglia and brainstem (Figure?1). A large number of cross-sectional studies have confirmed important risk factors and associations for CMBs, including age, hypertension, history of stroke (both ischaemic and haemorrhagic) and neuroimaging markers of small vessel disease including white matter changes and lacunar infarcts.6,7 There is increasing (albeit largely indirect) evidence that the distribution of CMBs reflects the underlying type of microangiopathy (Figure?1). Strictly lobar CMBs are considered likely to be due to CAA, because of their association with known risk factors for CAA including apolipoprotein E e4 genotype.8 Furthermore, an in vivo positron emission tomography amyloid-β imaging study using the ligand Pittsburgh compound B, found that CMBs in patients with CAA corresponded to local regions of high amyloid-β concentration.9 By contrast, deep CMBs are considered most likely to be due to hypertensive arteriopathy because of their associations with hypertension and other imaging manifestations of hypertensive small vessel disease.10 In clinical practice these arteriopathies (CAA and hypertension-related) are frequently likely to coexist and interact. Diagnostic criteria for CAA have been developed (the ‘Boston criteria’) (Table?1) with the aim of diagnosing CAA in vivo without recourse to tissue biopsy. These criteria include the presence of strictly lobar ICH, including CMBs, and have been shown to have very high specificity.11 However, the sensitivity of these criteria