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. 2013 Apr 9;80(15):1365-9.
doi: 10.1212/WNL.0b013e31828c2f52. Epub 2013 Mar 13.

Estimating cerebral microinfarct burden from autopsy samples

Affiliations

Estimating cerebral microinfarct burden from autopsy samples

M Brandon Westover et al. Neurology. .

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.

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Figures

Figure 1
Figure 1. Probability of 2 microinfarcts on routine postmortem examination vs total brain burden
Probability of finding 2 microinfarcts in routine pathologic examination of 9 microtome sections, as a function of the total number of microinfarcts randomly distributed throughout the brain volume, calculated using values from table 1. The light gray region (between 212 and 3,217 microinfarcts) contains values for which the probability exceeds 5%.
Figure 2
Figure 2. Estimate of total brain microinfarct burden vs number found on routine postmortem examination
Maximum likelihood estimates (red filled circles) with 90% confidence intervals of the total number of microinfarcts within the brain volume vs total number of microinfarcts seen in routine pathologic specimens, calculated using values from table 1.

Comment in

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