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on September 24, 2009

Stroke. 2009
Published online before print September 24, 2009, doi: 10.1161/STROKEAHA.109.560011
A more recent version of this article appeared on December 1, 2009
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Submitted on June 9, 2009
Revised on August 16, 2009
Accepted on August 28, 2009

Hemodynamic Compromise as a Cause of Internal Border-Zone Infarction and Cortical Neuronal Damage in Atherosclerotic Middle Cerebral Artery Disease

Hiroshi Yamauchi MD, PhD*; Ryuichi Nishii MD, PhD; Tatsuya Higashi MD, PhD; Shinya Kagawa MS; and Hidenao Fukuyama MD, PhD

From the Human Brain Research Center (H.Y., H.F.), Kyoto University Graduate School of Medicine, Kyoto, Japan; and the Research Institute (R.N., T.H., S.K.), Shiga Medical Center, Moriyama, Japan.

* To whom correspondence should be addressed. E-mail: yamauchi{at}kuhp.kyoto-u.ac.jp.

Background and Purpose—Hemodynamic compromise due to atherosclerotic middle cerebral artery (MCA) disease may induce internal border-zone infarction and cortical neuronal damage. This study aimed to determine whether internal border-zone infarction is associated with increased oxygen extraction fraction (OEF) and a decrease in central benzodiazepine receptors (BZRs) in the overlying cerebral cortex in atherosclerotic MCA disease.

Methods—We measured the OEF by using positron emission tomography and 15O gas in 100 nondisabled patients with atherosclerotic MCA disease in the chronic stage. On MRI, the infarcts were categorized as territorial, border-zone (external or internal), deep perforator, and superior perforator infarcts. In 62 patients, BZRs were measured using 11C-flumazenil. By using 3-dimensional stereotactic surface projections, the abnormally decreased BZR index ("BZR index") [(the extent of the pixels with Z score more than 2 compared with controls)x(average Z score in those pixels)] was calculated. In the hemisphere affected by MCA disease, the type of infarcts was correlated with the value of OEF or BZR index in the cerebral cortex of the MCA distribution.

Results—Compared with patients without internal border-zone infarcts, those with these infarcts (n=18) had significantly increased OEF and significantly high BZR index. Multivariate analysis revealed that internal border-zone infarction was independently associated with increased OEF and high BZR index.

Conclusions—In atherosclerotic MCA disease, internal border-zone infarction is associated with increased OEF and a decrease in BZRs in the overlying cerebral cortex, suggesting that hemodynamic compromise may induce internal border-zone infarction and cortical neuronal damage.


Key words: benzodiazepine receptor • internal border-zone infarction • middle cerebral artery disease • positron emission tomography