This Article Full Text Full Text (PDF) All Versions of this Article: 40/7/2382    most recent STROKEAHA.109.548974v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Greenberg, S. M. Articles by Smith, E. E. PubMed PubMed Citation Articles by Greenberg, S. M. Articles by Smith, E. E. Related Collections Computerized tomography and Magnetic Resonance Imaging Intracerebral Hemorrhage Pathology of Stroke

(Stroke. 2009;40:2382.)
© 2009 American Heart Association, Inc.

Original Contributions

Microbleeds Versus Macrobleeds

Evidence for Distinct Entities

Steven M. Greenberg, MD, PhD; R. N. Kaveer Nandigam, MD; Pilar Delgado, MD, PhD; Rebecca A. Betensky, PhD; Jonathan Rosand, MD, MSc; Anand Viswanathan, MD, PhD; Matthew P. Frosch, MD, PhD Eric E. Smith, MD, MPH

From the Hemorrhagic Stroke Research Program (S.M.G., R.N.K.N., P.D., J.R., A.V., E.E.S.), Department of Neurology, and the C.S. Kubik Laboratory in Neuropathology (M.P.F.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass; and the Department of Biostatistics (R.A.B.), Harvard School of Public Health, Boston, Mass.

Correspondence to Steven M. Greenberg, MD, PhD, MGH Stroke Research Center, 55 Fruit Street, CPZ 175, Suite 300, Boston, MA 02114. E-mail sgreenberg{at}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 cm³ and 27.5 cm³. 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.

Supplemental Materials and Methods