Progressive Cortical Neuronal Damage and Extracranial-Intracranial Bypass Surgery in Patients with Misery Perfusion.

BACKGROUND AND PURPOSE: Misery perfusion may cause selective neuronal damage in atherosclerotic ICA or MCA disease. Bypass surgery can improve misery perfusion and may prevent neuronal damage. On the other hand, surgery conveys a risk for neuronal damage. The purpose of this retrospective study was to determine whether progression of cortical neuronal damage in surgically treated patients with misery perfusion is larger than that in surgically treated patients without misery perfusion or medically treated patients with misery perfusion. MATERIALS AND METHODS: We evaluated the distribution of benzodiazepine receptors twice by using PET and 11C-labeled flumazenil in 18 surgically treated patients with atherosclerotic ICA or MCA disease (9 with misery perfusion and 9 without) and no perioperative stroke before and after bypass surgery; in 8 medically treated patients with misery perfusion and no intervening ischemic event; and in 7 healthy controls. We quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the MCA distribution and compared changes in the benzodiazepine receptor index among the 3 groups. RESULTS: The change in the benzodiazepine receptor index in surgically treated patients with misery perfusion (27.5 ± 15.6) during 7 ± 5 months was significantly larger than that in surgically treated patients without misery perfusion (-5.2 ± 9.4) during 6 ± 4 months (P < .001) and in medically treated patients with misery perfusion (3.2 ± 15.4) during 16 ± 6 months (P < .01). CONCLUSIONS: Progression of cortical neuronal damage in surgically treated patients with misery perfusion and no perioperative stroke may occur and may be larger than that in medically treated patients with misery perfusion and no intervening ischemic event.

Chronic hemodynamic compromise and cerebral ischemic events in asymptomatic or remote symptomatic large-artery intracranial occlusive disease.

BACKGROUND AND PURPOSE: In asymptomatic or remote symptomatic LAICOD, the risk of ischemic events is low in general, but there may be a subgroup of higher risk patients who require aggressive medical management. The purpose of this study was to determine whether chronic hemodynamic compromise is a predictor of ischemic events in asymptomatic or remote symptomatic LAICOD. MATERIALS AND METHODS: We prospectively studied 51 asymptomatic, 19 coexistent asymptomatic, and 19 remote (>6 months) symptomatic patients with atherosclerotic intracranial internal carotid artery or middle cerebral artery disease by using (15)O-PET. MP was defined as decreased CBF, increased OEF, and a decreased CBF/CBV ratio. All patients were followed up for 2 years or until occurrence of stroke or TIA or death. RESULTS: Bypass surgery was performed in 4 patients (2 with MP). Three cerebral ischemic events (1 TIA in an asymptomatic patient, 1 stroke, and 1 TIA in a remote symptomatic patient) occurred in the vascular territory ipsilateral to LAICOD. Kaplan-Meier analysis with censoring at the time of bypass surgery revealed that the incidence of ipsilateral ischemic events in patients with MP (2/5) was significantly higher than that in patients without MP (1/84) (log-rank test; P < .0001). The relative risk conferred by MP was 83.1 (95% confidence interval, 6.8-1017.4; P < .001). The incidence of ipsilateral ischemic events in patients with decreased CBF/CBV (2/9) was also significantly higher than that of patients without it (1/80) (P = .0001). CONCLUSIONS: Chronic hemodynamic compromise may be a predictor of ischemic events in both asymptomatic and remote symptomatic LAICOD.

Pattern of collaterals, type of infarcts, and haemodynamic impairment in carotid artery occlusion.

BACKGROUND: In internal carotid artery (ICA) occlusion, increased oxygen extraction fraction (OEF) indicates inadequate collateral blood flow distal to the occlusion, which may be caused by poor function of collateral pathways. In ICA occlusion, the circle of Willis may be the major collateral pathway, while the collaterals through the ophthalmic artery and leptomeningeal vessels may be recruited when collateral flow through the circle of Willis is inadequate. Conversely, ischaemic lesions may affect the adequacy of collateral blood flow by reducing the metabolic demand of the brain. OBJECTIVE: To determine whether the pattern of collateral pathways and the type of infarcts are independent predictors of OEF in ICA occlusion. METHODS: We studied 42 patients with symptomatic ICA occlusion. The presence of Willisian, ophthalmic, or leptomeningeal collaterals was evaluated by conventional four vessel angiography. The infarcts on magnetic resonance imaging were categorised as territorial, border zone (external or internal), striatocapsular, lacunar, and other white matter infarcts. The value of OEF in the affected hemisphere was measured with positron emission tomography as an index of haemodynamic impairment. RESULTS: Using multivariate analysis, the presence of any ophthalmic or leptomeningeal collaterals and the absence of striatocapsular infarcts were significant and independent predictors of increased OEF. CONCLUSIONS: In patients with symptomatic ICA occlusion, the supply of collateral flow, which is affected by the pattern of collateral pathways, and the metabolic demand of the brain, which is affected by the type of infarct, may be important factors determining the severity of haemodynamic impairment.

Oxygen extraction fraction and acetazolamide reactivity in symptomatic carotid artery disease.

OBJECTIVE: It has been proposed that cerebral blood flow (CBF) response to acetazolamide may be reduced according to the degree of autoregulatory vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the CBF response may be absent in regions with increased OEF where vasodilation may be maximal in response to reduced perfusion pressure. The objective of this study was to test this hypothesis. METHODS: Positron emission tomography (PET) was used to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide was measured. The correlation between the change in CBF during acetazolamide administration and the baseline value of OEF in the affected hemisphere was examined. RESULTS: The baseline OEF value was inversely and non-linearly correlated with the percentage change in CBF during acetazolamide administration (R(2) = 0.25, p = 0.02). There was an upward trend of OEF with diminishing acetazolamide response below a critical level around zero response. Acetazolamide response less than 6.65% over baseline (sensitivity 100%, specificity 89%, positive predictive value 50%, negative predictive value 100%) was established as most helpful in predicting abnormally high OEF. CONCLUSIONS: The inverse, non-linear relationship between OEF and CBF response to acetazolamide suggests that these two measurements may not identify haemodynamic impairment in the same patients.

Effects of acetazolamide on cerebral blood flow, blood volume, and oxygen metabolism: a positron emission tomography study with healthy volunteers.

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

Quantitative comparison of the bolus and steady-state methods for measurement of cerebral perfusion and oxygen metabolism: positron emission tomography study using 15O-gas and water.

To evaluate a new simplified bolus method for measurement of cerebral perfusion and metabolism, the parametric images with that method were compared with those obtained from the conventional steady-state method with 15O-gas. The new method also provided images of arterial blood volume (V0), which is a different parameter from cerebral blood volume (CBV) obtained using a C15O technique. Seven healthy volunteers and 10 patients with occlusive cerebrovascular diseases underwent positron emission tomography (PET) scans with both methods. Three-weighted integration was applied to calculate regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) in the bolus method. Global and regional CBF and CMRO2 in volunteers were compared between the two methods and used as control data. Regional values in patients also were evaluated to observe differences between the bilateral hemispheres. Both rCBF and rCMRO2 were linearly well correlated between the two methods, although global difference in CMRO2 was significant. The difference in each parametric image except for V0 was significant between the bilateral hemispheres in patients. The bolus method can simplify oxygen metabolism studies and yield parametric images comparable with those with the steady-state method, and can allow for evaluation of V0 simultaneously. Increase in CBV without a change in V0 suggested the increase might mainly be caused by venous dilatation in the ischemic regions.