Cerebral Microbleeds: A Review of Clinical, Genetic, and Neuroimaging Associations

Paul A Yates,Christopher C Rowe,Colin L Masters,Kathryn A Ellis,Patricia M Desmond,Victor L Villemagne

doi:10.3389/fneur.2013.00205

Abstract

Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer’s disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using 11C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage – particularly in the setting of anticoagulation – and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.

Highlights

Symptomatic Intracerebral Hemorrhage (ICH) affects 30–40 per 10,000 annually [1], and can have devastating clinical outcomes [2]
MB in deep subcortical or infratentorial areas are usually associated with the presence of hypertensive disease or vascular risk factors (VRF) [16, 34], with lipohyalinosis being the predominant finding at post-mortem [33]
Mutations associated with microbleeds in familial conditions include NOTCH-3 in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) [53], APP E693Q and D694N in Dutch-type [40, 54] or Iowatype [55] cerebral amyloid angiopathy (CAA), and APP and presenilin mutations in familial Alzheimer’s disease (AD) [56, 57]

Summary

INTRODUCTION

Symptomatic Intracerebral Hemorrhage (ICH) affects 30–40 per 10,000 annually [1], and can have devastating clinical outcomes [2]. Presence of hypertensive arteriolosclerosis and cerebral amyloid angiopathy (CAA) are contributory in an estimated 78–88% of primary ICH [9] In both of these conditions, prior to emergence of symptomatic ICH, there may be evidence of smaller, possibly subclinical hemorrhages, reflective of underlying vascular fragility. These lesions, termed cerebral “microbleeds” (microbleeds) may be an indicator of increased risk for future macroscopic hemorrhage [10, 11]. MB in deep subcortical or infratentorial areas are usually associated with the presence of hypertensive disease or vascular risk factors (VRF) [16, 34], with lipohyalinosis being the predominant finding at post-mortem [33]. Mutations associated with microbleeds in familial conditions include NOTCH-3 in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) [53], APP E693Q and D694N in Dutch-type [40, 54] or Iowatype [55] CAA, and APP and presenilin mutations in familial AD [56, 57]

MICROBLEEDS AND NEUROIMAGING

Findings

CONCLUSION