title: Microbleeds versus macrobleeds: evidence for distinct entities.
abstract: 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.
authors.affiliation: MGH Stroke Research Center, Harvard Medical School, Boston, MA 02114, USA. sgreenberg@partners.org
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: R N Kaveer
authors.initials: RN
authors.lastname: Nandigam
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
mesh_terms: 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