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April 09, 2013; 80 (15) Article

Estimating cerebral microinfarct burden from autopsy samples

M. Brandon Westover, Matt T. Bianchi, Chunhui Yang, Julie A. Schneider, Steven M. Greenberg
First published March 13, 2013, DOI: https://doi.org/10.1212/WNL.0b013e31828c2f52
M. Brandon Westover
From the Hemorrhagic Stroke Research Program (M.B.W., M.T.B., S.M.G.), Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston; and Rush Alzheimer's Disease Center (C.Y., J.A.S.), Department of Pathology, Rush University Medical Center, Chicago, IL.
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Matt T. Bianchi
From the Hemorrhagic Stroke Research Program (M.B.W., M.T.B., S.M.G.), Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston; and Rush Alzheimer's Disease Center (C.Y., J.A.S.), Department of Pathology, Rush University Medical Center, Chicago, IL.
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Chunhui Yang
From the Hemorrhagic Stroke Research Program (M.B.W., M.T.B., S.M.G.), Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston; and Rush Alzheimer's Disease Center (C.Y., J.A.S.), Department of Pathology, Rush University Medical Center, Chicago, IL.
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Julie A. Schneider
From the Hemorrhagic Stroke Research Program (M.B.W., M.T.B., S.M.G.), Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston; and Rush Alzheimer's Disease Center (C.Y., J.A.S.), Department of Pathology, Rush University Medical Center, Chicago, IL.
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Steven M. Greenberg
From the Hemorrhagic Stroke Research Program (M.B.W., M.T.B., S.M.G.), Department of Neurology, Massachusetts General Hospital, and Harvard Medical School, Boston; and Rush Alzheimer's Disease Center (C.Y., J.A.S.), Department of Pathology, Rush University Medical Center, Chicago, IL.
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Citation
Estimating cerebral microinfarct burden from autopsy samples
M. Brandon Westover, Matt T. Bianchi, Chunhui Yang, Julie A. Schneider, Steven M. Greenberg
Neurology Apr 2013, 80 (15) 1365-1369; DOI: 10.1212/WNL.0b013e31828c2f52

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Abstract

Objective: To estimate whole-brain microinfarct burden from microinfarct counts in routine postmortem examination.

Methods: We developed a simple mathematical method to estimate the total number of cerebral microinfarcts from counts obtained in the small amount of tissue routinely examined in brain autopsies. We derived estimates of total microinfarct burden from autopsy brain specimens from 648 older participants in 2 community-based clinical-pathologic cohort studies of aging and dementia.

Results: Our results indicate that observing 1 or 2 microinfarcts in 9 routine neuropathologic specimens implies a maximum-likelihood estimate of 552 or 1,104 microinfarcts throughout the brain. Similar estimates were obtained when validating in larger sampled brain volumes.

Conclusions: The substantial whole-brain burden of cerebral microinfarcts suggested by even a few microinfarcts on routine pathologic sampling suggests a potential mechanism by which these lesions could cause neurologic dysfunction in individuals with small-vessel disease. The estimation framework developed here may generalize to clinicopathologic correlations of other imaging-negative micropathologies.

GLOSSARY

CI=
confidence interval;
DWI=
diffusion-weighted imaging;
MAP=
Memory and Aging Project;
ML=
maximum likelihood;
ROS=
Religious Orders Study

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Editorial, page 1358

  • Received August 6, 2012.
  • Accepted in final form November 13, 2012.
  • © 2013 American Academy of Neurology
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