Microbleeds versus macrobleeds: evidence for distinct entities.
OBJECTIVE
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.
Greenberg
Steven M
SM
MGH Stroke Research Center, Harvard Medical School, Boston, MA 02114, USA. sgreenberg@partners.org
Nandigam
R N Kaveer
RN
Delgado
Pilar
P
Betensky
Rebecca A
RA
Rosand
Jonathan
J
Viswanathan
Anand
A
Frosch
Matthew P
MP
Smith
Eric E
EE
D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications*; D002536:Cerebral Arteries / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000209:etiology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012189:Retrospective Studies