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Microbleeds versus macrobleeds: evidence for distinct entities
Steven M Greenberg1, R N Kaveer Nandigam, Pilar Delgado
1MGH Stroke Research Center, Harvard Medical School, Boston, MA 02114, USA. sgreenberg@partners.org
Background And Purpose:
Small, asymptomatic microbleeds commonly accompany larger symptomatic macrobleeds. It is unclear whether microbleeds and macrobleeds represent arbitrary categories within a single continuum versus truly distinct events with separate pathophysiologies.
Methods:
We performed 2 complementary retrospective analyses. In a radiographic analysis, we measured and plotted the volumes of all hemorrhagic lesions detected by gradient-echo MRI among 46 consecutive patients with symptomatic primary lobar intracerebral hemorrhage diagnosed as probable or possible cerebral amyloid angiopathy. In a second neuropathologic analysis, we performed blinded qualitative and quantitative examinations of amyloid-positive vessel segments in 6 autopsied subjects whose MRI scans demonstrated particularly high microbleed counts (>50 microbleeds on MRI, n=3) or low microbleed counts (<3 microbleeds, n=3).
Results:
Plotted on a logarithmic scale, the volumes of 163 hemorrhagic lesions identified on scans from the 46 subjects fell in a distinctly bimodal distribution with mean volumes for the 2 modes of 0.009 cm(3) and 27.5 cm(3). The optimal cut point for separating the 2 peaks (determined by receiver operating characteristics) corresponded to a lesion diameter of 0.57 cm. On neuropathologic analysis, the high microbleed-count autopsied subjects showed significantly thicker amyloid-positive vessel walls than the low microbleed-count subjects (proportional wall thickness 0.53+/-0.01 versus 0.37+/-0.01; P<0.0001; n=333 vessel segments analyzed).
Conclusions:
These findings suggest that cerebral amyloid angiopathy-associated microbleeds and macrobleeds comprise distinct entities. Increased vessel wall thickness may predispose to formation of microbleeds relative to macrobleeds.
Insights
Cerebral amyloid angiopathy-associated microbleeds and macrobleeds appear to be distinct conditions, not a single continuum. Thicker vessel walls may contribute to microbleed formation in this condition.
Area of Science:
- Neurology
- Radiology
- Pathology
Background:
- Small, asymptomatic microbleeds often coexist with larger symptomatic macrobleeds.
- The relationship between microbleeds and macrobleeds in cerebral amyloid angiopathy (CAA) remains unclear, questioning if they are part of a single spectrum or distinct pathological events.
Purpose of the Study:
- To investigate whether microbleeds and macrobleeds in CAA represent distinct entities or a continuous spectrum.
- To explore potential pathophysiological differences between microbleeds and macrobleeds in CAA.
Main Methods:
- Retrospective analysis of gradient-echo MRI scans from 46 patients with symptomatic lobar intracerebral hemorrhage due to probable or possible CAA.
- Radiographic analysis of hemorrhagic lesion volumes and neuropathologic examination of amyloid-positive vessel segments in autopsied subjects with high versus low microbleed counts.
Main Results:
- Hemorrhagic lesion volumes exhibited a bimodal distribution, suggesting two distinct size categories.
- Neuropathologic analysis revealed significantly thicker amyloid-positive vessel walls in autopsied subjects with a high microbleed burden compared to those with a low burden.
Conclusions:
- Findings suggest that microbleeds and macrobleeds in CAA are distinct entities.
- Increased cerebral amyloid angiopathy vessel wall thickness may be a predisposing factor for microbleed development.
