Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic moyamoya disease: subanalysis of a prospective cohort.

OBJECTIVE: Adult patients with ischemic moyamoya disease (MMD) who receive treatment with antiplatelet drugs reportedly show improvements in neuropsychological test scores after around 2 years. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, results in better improvement of cognitive function among non-surgical adult patients showing ischemic MMD without severe hemodynamic compromise. METHODS: Sixty-six patients without cerebral misery perfusion on 15O gas positron emission tomography were treated with pharmacotherapy alone. Patients ≥50 years old and <50 years old initially received clopidogrel and cilostazol, respectively. Any patient suffering side effects of the antiplatelet drug switched to the other antiplatelet drug. Neuropsychological tests were performed at study entry and at the end of the 2-year follow-up, and differences in each neuropsychological test score between the two time points (second test score - first test score) were calculated and defined as Δ scores. RESULTS: Among the five neuropsychological tests, Δ scores for two tests were significantly greater in patients treated with cilostazol (n = 36) than in those treated with clopidogrel (n = 30), and Δ scores of the remaining three tests did not differ between patient groups. Based on Δ scores, 15 patients (23%) were defined as showing interval cognitive improvement. On multivariate analysis, cilostazol administration (95% confidence interval, 1.19-193.98; P = 0.0361) represented an independent predictor of interval cognitive improvement. CONCLUSIONS: Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic MMD.

Comparison of Effects between Clopidogrel and Cilostazol on Cerebral Perfusion in Nonsurgical Adult Patients with Symptomatically Ischemic Moyamoya Disease: Subanalysis of a Prospective Cohort.

BACKGROUND AND PURPOSE: Adult patients with symptomatically ischemic moyamoya disease (MMD) initially undergo medical treatment alone including antiplatelet drugs when symptomatic cerebral hemispheres do not exhibit hemodynamic compromise. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, provides better improvement of cerebral perfusion in such patients. METHODS: All patients without cerebral misery perfusion on 15O gas positron emission tomography (PET) did not undergo revascularization surgery and were treated with medication alone, including antiplatelet therapy. Patients ≥50years and <50years initially received clopidogrel and cilostazol, respectively. When a patient suffered side effects of an antiplatelet drug, they were switched to the other antiplatelet drug. Cerebral blood flow (CBF) in the symptomatic hemisphere was measured at inclusion and at 2years after inclusion using 15O gas PET. RESULTS: Of 68 patients, 31 and 38 were treated with clopidogrel and cilostazol, respectively, for 2years after inclusion. For patients treated with clopidogrel, CBF did not differ between first and second PET. For patients treated with cilostazol, CBF was significantly greater in the second PET than in the first PET. On multivariate analysis, cilostazol administration was an independent predictor of CBF improvement in the symptomatic hemisphere (95% confidence interval, 1.34-139.20; P =.0271). CONCLUSIONS: Cilostazol improves cerebral perfusion better than clopidogrel in adult patients with symptomatically ischemic MMD not accompanied by misery perfusion.

Accuracy of brain perfusion single-photon emission computed tomography for detecting misery perfusion in adult patients with symptomatic ischemic moyamoya disease.

OBJECTIVE: The purpose of the present study was to determine how accurately relative cerebral blood flow (RCBF) and relative cerebrovascular reactivity (RCVR) to acetazolamide assessed using brain perfusion single-photon emission computed tomography (SPECT) detected misery perfusion identified on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). METHODS: Oxygen extraction fraction (OEF), RCBF, and RCVR were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine SPECT without and with acetazolamide challenge, respectively, in 45 patients. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories in the symptomatic cerebral hemisphere and in the ipsilateral cerebellar hemisphere using a three-dimensional stereotaxic ROI template. For RCBF and RCVR to acetazolamide, the ratio of the MCA ROI to cerebellar ROI was calculated. Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest and lowest OEF value (two ROIs per patient) was selected for analyses. RESULTS: A significant square or linear correlation was observed between the OEF and RCBF (correlation coefficient, 0.780) or RCVR (correlation coefficient, - 0.345), respectively. The area under the receiver operating characteristic curve for detecting misery perfusion (OEF > 51.3%) was significantly greater for the RCBF than for the RCVR (difference between areas, 0.221; p < 0.0001). Sensitivity, specificity, and positive- and negative-predictive values for the RCBF for detecting misery perfusion were 100, 91, 67, and 100%, respectively. The specificity and positive-predictive value did not differ between the combination of the RCBF and RCVR and the CBF ratio alone. CONCLUSIONS: RCBF assessed using brain perfusion SPECT detects misery perfusion with high sensitivity, a high negative-predictive value, and a low positive-predictive value in adult patients with ischemic MMD. The accuracy of RCVR to acetazolamide assessed using brain perfusion SPECT is lower than that of RCBF.

Preoperative brain temperature imaging on proton magnetic resonance spectroscopy predicts hemispheric ischemia during carotid endarterectomy for unilateral carotid stenosis with inadequate collateral blood flow.

Objective Preoperative magnetic resonance (MR) angiography sometimes shows the absence of collateral flow via the circle of Willis. This study examined whether brain temperature (BT) imaging on multi-voxel proton MR spectroscopy after this finding increases the accuracy of predicting hemispheric ischemia during internal carotid artery (ICA) clamping during endarterectomy for patients with symptomatic unilateral carotid stenosis. Methods In 52 patients with ICA stenosis (≥70%) and absence of collateral blood flow via the circle of Willis on preoperative MR angiography, BT imaging was displayed using proton multi-voxel MR spectroscopy. The difference between BTs in the affected and contralateral hemispheres (BTaffected hemisphere - BTcontralateral hemisphere) in the deep white matter of the centrum semiovale was calculated and defined as hemispheric ΔBT. Development of cerebral hemispheric ischemia during ICA clamping was determined from intraoperative electroencephalography (EEG). Results Multivariate analysis revealed that high preoperative hemispheric ΔBT was significantly associated with development of EEG-defined hemispheric ischemia (95% confidence intervals [CIs], 5.376-15.452; p = 0.006). The positive-predictive value for development of EEG-defined hemispheric ischemia was significantly greater for preoperative hemispheric ΔBT following preoperative MR angiography (95%CI, 42-87%) than for preoperative MR angiography alone (95%CI, 13-37%). Conclusions For patients without collateral flow via the circle of Willis, BT imaging increases the predictive accuracy for development of hemispheric ischemia during ICA clamping during CEA.

Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease.

The present study examined whether preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease. Among 65 adult patients with ischemic moyamoya disease, 19 had misery perfusion in the precentral region on preoperative 15O positron emission tomography and underwent arterial bypass surgery for that region. Brain technetium-99 m-labeled ethyl cysteinate dimer single-photon emission computed tomography (SPECT) was preoperatively performed with and without hyperventilation challenge and relative cerebrovascular contractile reactivity to hypocapnia (RCVCRhypocap) (%/mmHg) was calculated in the precentral region. Development of cerebral hyperperfusion syndrome was determined using perioperative changes of symptoms and brain N-isopropyl-p-[123I]-iodoamphetamine SPECT performed after surgery. RCVCRhypocap was significantly lower in the 6 patients with cerebral hyperperfusion syndrome (-2.85 ± 1.10%/mmHg) than in the 13 patients without cerebral hyperperfusion syndrome (0.18 ± 1.97%/mmHg; p = 0.0050). Multivariate analysis demonstrated low RCVCRhypocap as an independent predictor of cerebral hyperperfusion syndrome (95% confidence interval, 0.04-0.96; p = 0.0433). Preoperatively reduced cerebrovascular contractile reactivity to hypocapnia by hyperventilation is associated with development of cerebral hyperperfusion syndrome after arterial bypass surgery for adult patients with cerebral misery perfusion due to ischemic moyamoya disease.