Microhemorrhages (MHs), also known as cerebral microbleeds, are tiny deposits of blood breakdown products, primarily hemosiderin, found within the brain tissue. These lesions represent a common form of cerebral small vessel disease, indicating minute leakages from fragile blood vessels. Advances in neuroimaging have transformed the recognition of these silent bleeds into a significant biomarker. While MHs are not typically symptomatic, their presence signals underlying vascular instability and future neurological decline.
Visualizing Microhemorrhages
Identifying these minute lesions requires specialized magnetic resonance imaging (MRI) sequences sensitive to the magnetic properties of iron. Detection typically uses T2-weighted gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI). These sequences make the iron deposits in hemosiderin appear as distinct, small, dark spots because iron dephases the surrounding magnetic field.
The small, spherical appearance of these lesions is often exaggerated on the scan, creating a “blooming effect” that makes them seem larger than they are. Although their actual size is measured in microns, they typically appear on MRI scans as punctate foci between 2 and 10 millimeters in diameter. Modern SWI can detect lesions as small as 1 millimeter, leading to a higher reported prevalence in recent studies.
The location of MHs provides important clues about the underlying cause of vascular damage. Deep lesions, such as those in the basal ganglia, thalamus, and brainstem, are often associated with chronic high blood pressure. In contrast, MHs located in the cerebral cortex and at the gray/white matter junction are typically linked to a different small vessel pathology. This distinction in topography helps neurologists categorize the type of small vessel disease present.
Root Causes and Risk Factors
The formation of MHs is driven by two main pathological processes that weaken small cerebral blood vessels. The most common cause is hypertensive vasculopathy, where chronic, uncontrolled high blood pressure damages deep penetrating arteries. This damage leads to microaneurysms, rupture, and microbleeds primarily located in the deep brain regions. Advanced age is also a risk factor, as the natural stiffening and degeneration of blood vessels increase fragility.
The other major cause is cerebral amyloid angiopathy (CAA), involving the deposition of amyloid-beta protein in the walls of cortical arteries and arterioles. This protein accumulation weakens the vessel structure, making it prone to leakage, and drives microbleeds in the lobar (cortical) regions. Genetic predisposition also plays a role, particularly the APOE e4 allele, which is strongly associated with CAA and a higher burden of lobar microbleeds.
The APOE e4 allele, a known risk factor for Alzheimer’s disease, significantly increases the risk for MHs, especially in individuals with mild cognitive impairment or Alzheimer’s. Certain medical treatments, such as antiplatelet or anticoagulant therapies, do not cause initial vessel damage but act as a secondary risk factor. These medications increase the likelihood of new MHs forming and raise the risk that a microbleed will progress into a larger, symptomatic hemorrhage. Therefore, the decision to use these medications must carefully weigh stroke prevention against the increased bleeding risk posed by existing MHs.
Clinical Relevance: Predicting Neurological Decline
MHs are recognized as a biomarker for predicting future neurological events. Their presence indicates a vulnerable cerebrovascular system and signals an elevated risk for subsequent stroke, including both hemorrhagic and ischemic types.
The risk for symptomatic hemorrhagic stroke, or intracerebral hemorrhage (ICH), is high and increases steeply with the number of MHs. Patients with five or more MHs can have an up to 4.55-fold higher risk for symptomatic ICH compared to those without. The location of the lesions also matters: lobar MHs are more strongly linked to hemorrhagic events, while deep MHs are associated with both hemorrhagic and ischemic stroke.
MHs also serve as a marker for developing or progressing cognitive impairment and are frequently seen in individuals with vascular dementia. In Alzheimer’s disease, the MH count is positively correlated with the accumulation of amyloid-beta and tau pathology. Their strong association with small vessel disease and stroke risk means they contribute significantly to the vascular component of dementia.
Strategies for Mitigation
The primary strategy for mitigating the risk associated with MHs focuses on aggressive management of underlying vascular risk factors. Strict control of blood pressure is paramount, especially in patients with deep-seated MHs resulting from hypertensive vasculopathy. Evidence suggests that maintaining a systolic blood pressure target below 130 mmHg can help prevent the formation of new microbleeds.
The use of antiplatelet and anticoagulant medications presents a complex clinical dilemma. These drugs are often necessary to prevent serious ischemic events, yet they heighten the risk of an existing MH leading to a major hemorrhage. Current guidance suggests that in patients who have experienced an ischemic stroke or transient ischemic attack, the presence of fewer than five MHs should not prevent the use of antiplatelet therapy.
When the MH burden is high (five or more lesions), or when the MHs are exclusively lobar, balancing ischemic and hemorrhagic prevention becomes critical. Physicians must carefully weigh the individual patient’s risk profile, often favoring close monitoring or alternative strategies. Lipid management is also challenging, as some studies suggest that very low levels of LDL cholesterol may paradoxically increase the risk for MHs. The approach to a patient with MHs requires a highly individualized strategy, prioritizing vascular stability while balancing competing risks.