Makindo Medical Notes

Related Subjects: |Neurological History taking |Causes of Stroke

Introduction

Cerebral microbleeds (CMBs) are small, chronic deposits of hemosiderin (an iron-storage complex) found within the brain parenchyma. They are the result of leakage from small blood vessels and are associated with various neurological conditions. Due to their superparamagnetic properties, these hemosiderin deposits are detectable using specific magnetic resonance imaging (MRI) sequences sensitive to magnetic susceptibility effects.

About

• CMBs are increasingly recognized for their clinical significance in conditions such as dementia, ischemic and hemorrhagic stroke, and normal aging.
• They are considered biomarkers of small vessel disease and indicate microangiopathic changes within the brain.
• Detection has improved with advanced MRI techniques, particularly those that exploit magnetic susceptibility differences.

Etiology

• CMBs represent small foci of chronic blood product deposition in normal or near-normal brain tissue.
• They result from structural abnormalities in small vessels, leading to blood leakage and hemosiderin deposition.
• Size definitions vary but typically range from a minimum of 2 mm up to a maximum diameter of 5-10 mm.

Common Causes

• Normal Aging: The prevalence of CMBs increases with age due to cumulative vascular changes.
• Hypertensive Vasculopathy: Chronic hypertension causes lipohyalinosis and fibrinoid necrosis of small penetrating arteries, leading to microbleeds, especially in deep brain regions like the basal ganglia, thalamus, brainstem, and cerebellum.
• Cerebral Amyloid Angiopathy (CAA): Deposition of amyloid-beta in vessel walls weakens them, leading to microbleeds predominantly in lobar cortical regions, particularly the occipital lobe.
• Alzheimer's Disease: Associated with both CAA and neurodegeneration, increasing the likelihood of microbleeds.
• Traumatic Brain Injury: Diffuse axonal injury from head trauma can cause microhemorrhages due to shearing forces on vessels.
• Hemorrhagic Transformation of Ischemic Stroke: Reperfusion injury can lead to microbleeds in ischemic areas.
• Other Causes:
• Metastatic melanoma (due to hemorrhagic metastases)
• Cavernous malformations
• Anticoagulant or antithrombotic therapy
• Radiation-induced vasculopathy

Imaging and Investigations

Detection of cerebral microbleeds relies on MRI sequences sensitive to magnetic susceptibility effects caused by hemosiderin deposits.

• T2*-Weighted Gradient Echo (GRE) MRI: An early technique sensitive to magnetic susceptibility, revealing microbleeds as hypointense (dark) lesions due to the "blooming" effect.
• Susceptibility Weighted Imaging (SWI): A more advanced MRI sequence combining magnitude and phase information to enhance sensitivity to venous blood, iron, and calcium. SWI is more sensitive than T2* GRE in detecting microbleeds.
• Size and Appearance: Microbleeds appear as small, rounded or ovoid hypointense foci without surrounding edema or mass effect.
• Blooming Effect: Hemosiderin deposits cause a signal void larger than their actual size due to magnetic susceptibility, which is more pronounced on T2* and SWI sequences.

Clinical Significance

• Risk of Hemorrhagic Stroke: The presence of multiple microbleeds is associated with an increased risk of intracerebral hemorrhage, especially in patients with hypertension or cerebral amyloid angiopathy.
• Anticoagulation Considerations: Microbleeds may influence decisions regarding anticoagulant therapy due to the potential increased risk of bleeding.
• Cognitive Impairment: CMBs are linked to cognitive decline and may contribute to the pathology of vascular dementia and Alzheimer's disease.
• Small Vessel Disease Indicator: Serve as markers for underlying cerebral small vessel disease, which can manifest as lacunar strokes, white matter hyperintensities, and vascular cognitive impairment.
• Predictive Value: Location and number of CMBs can help predict future cerebrovascular events and guide clinical management.

Microbleed Distribution Patterns

• Lobar Regions: Microbleeds in cortical-subcortical areas are often associated with cerebral amyloid angiopathy.
• Deep Brain Structures: Microbleeds in the basal ganglia, thalamus, and brainstem are typically related to hypertensive vasculopathy.
• Infratentorial Regions: Microbleeds in the cerebellum and brainstem may also be linked to hypertension or other vasculopathies.

Management Implications

• Risk Assessment: Identification of CMBs can influence stroke prevention strategies and management of hypertension.
• Medication Decisions: May affect the use of antithrombotic or thrombolytic therapies due to bleeding risk considerations.
• Monitoring Progression: Serial imaging can track the development of new microbleeds or growth of existing ones.
• Patient Counseling: Informing patients about the implications of CMBs and lifestyle modifications to reduce vascular risk factors.

Comparing T2* GRE and SWI

SWI provides greater sensitivity and detail in detecting cerebral microbleeds compared to T2*-weighted GRE sequences. The image on the right demonstrates more extensive visualization of cerebral amyloid angiopathy (CAA) and microbleeds.

Comparison of T2*-weighted GRE (left) and SWI (right) imaging in detecting cerebral microbleeds associated with CAA. Image courtesy of Wikimedia Commons (Link).

Limitations and Considerations

• False Positives: Certain structures or conditions can mimic microbleeds on MRI, such as:
  • Calcifications
  • Iron deposits (e.g., in neurodegenerative diseases)
  • Vessel flow voids
• Standardization: Variability in MRI protocols and definitions of microbleed size can affect detection rates and comparisons across studies.
• Clinical Correlation: Not all microbleeds are symptomatic, and their clinical relevance should be interpreted in the context of the patient's overall condition.

Conclusion

Cerebral microbleeds are important neuroimaging findings that provide insights into underlying small vessel pathology and cerebrovascular risk. Advanced MRI techniques like SWI enhance their detection, contributing to better risk stratification and management of patients with neurological conditions. Ongoing research aims to further understand the implications of CMBs in disease progression and treatment outcomes.

References

• Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8(2):165-174.
• Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822-838.
• Yakushiji Y, Noguchi T, Hara M, et al. Distribution of cerebral microbleeds in patients with Alzheimer's disease: a 7 T MRI study. J Alzheimers Dis. 2012;31(1):29-37.
• Shams S, Martola J, Cavallin L, et al. SWI or T2*: which MRI sequence to use in the detection of cerebral microbleeds? The MAGNO-SCANS study. PLoS One. 2015;10(3):e0119892.