Selective neuronal damage and chronic hemodynamic cerebral ischemia

OBJECTIVE: In atherothrombotic internal carotid artery or middle cerebral artery (MCA) occlusive disease, chronic hemodynamic compromise may increase the risk for cerebral ischemic damage. To determine whether selective neuronal damage demonstrated as a decrease in central benzodiazepine receptor (BZR) in the normal-appearing cerebral cortex is associated with increased oxygen extraction fraction (OEF) (misery perfusion). METHODS: We measured BZR and OEF using positron emission tomography in 105 nondisabled patients with atherothrombotic internal carotid artery or MCA occlusive disease and no cortical infarction. By using three-dimensional stereotactic surface projections and the stereotactic extraction estimation method, without correction for partial volume effects, the abnormally decreased BZR index [(the extent of the pixels with Z-score more than 2 compared with controls) x (average Z-score in those pixels)] in the cerebral cortex of the MCA distribution with arterial disease was calculated, and it was found to be correlated with the mean hemispheric value of OEF and several clinical variables. RESULTS: All patients had pixels with abnormally decreased BZR, with the extent varying from 0.04 to 60.91%. Multivariate analysis showed that the abnormally decreased BZR index was positively correlated with the value of OEF and the history of stroke, whereas it was negatively correlated with the presence of hypercholesterolemia with statin treatment. Follow-up examinations of 17 patients without ischemic episode showed that a decrease of BZR was associated with an increase of OEF. INTERPRETATION: In atherothrombotic internal carotid artery or MCA occlusive disease, misery perfusion may cause selective neuronal damage, and statins might have beneficial effects against neuronal damage.