Yasunori Suga

Postoperative Cortical Neural Loss Associated With Cerebral Hyperperfusion and Cognitive Impairment After Carotid Endarterectomy 123I-iomazenil SPECT Study

Background and Purpose— Although cerebral hyperperfusion after carotid endarterectomy (CEA) often impairs cognitive function, MRI does not always demonstrate structural brain damage associated with postoperative cognitive impairment. The purpose of the present study was to determine whether postoperative cortical neural loss, which can be detected by 123I-iomazenil single-photon emission CT, is associated with cerebral hyperperfusion after CEA and whether it correlates with postoperative cognitive impairment. Methods— In 60 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>70%), cerebral blood flow was measured using N-isopropyl-p-[123I]-iodoamphetamine single-photon emission CT before and immediately after CEA and on the third postoperative day. The distribution of benzodiazepine receptor binding potential in the cerebral cortex was assessed using 123I-iomazenil single-photon emission CT before and 1 month after surgery and was analyzed using 3-dimensional stereotactic surface projection. Neuropsychological testing was also performed preoperatively and at the first postoperative month. Results— Post-CEA hyperperfusion and postoperative cognitive impairment were observed in 9 patients (15%) and 8 patients (13%), respectively. Post-CEA hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 2.765 to 148.804; P=0.0031). Post-CEA hyperperfusion (95% CIs, 1.183 to 229.447; P=0.0370) and postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 1.003 to 77.381; P=0.0496) were also significantly associated with postoperative cognitive impairment. Conclusions— Cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment.

Magnetic resonance imaging in patients with cerebral hyperperfusion and cognitive impairment after carotid endarterectomy

OBJECT Cerebral hyperperfusion after carotid endarterectomy (CEA) impairs cognitive function and is often detected on cerebral blood flow (CBF) imaging. The purpose of the present study is to investigate structural brain damage seen on magnetic resonance (MR) images obtained in patients with cerebral hyperperfusion and cognitive impairment after CEA. METHODS One hundred and fifty-eight patients with ipsilateral internal carotid artery stenosis (> or = 70%) underwent CEA. Neuropsychological testing was performed preoperatively and at the 1st postoperative month. Cerebral blood flow was measured using single-photon emission computed tomography before, immediately after, and 3 days after surgery. Magnetic resonance imaging was performed before and 1 day after surgery. In patients with post-CEA hyperperfusion (defined as a CBF increase > or = 100% compared with preoperative values) on CBF imaging, MR images were also obtained on the 3rd postoperative day, the day on which hyperperfusion syndrome developed, and 1 month after the operation. RESULTS The incidence of postoperative cognitive impairment was significantly higher in patients with post-CEA hyperperfusion on CBF imaging (12 [75%] of 16 patients) than in those without (6 [4%] of 142 patients; p < 0.0001). Only 1 of 5 patients with cerebral hyperperfusion syndrome developed reversible brain edema in the cerebral hemisphere ipsilateral to the CEA on MR images obtained on the day hyperperfusion syndrome occurred. However, postoperative cognitive impairment developed in all 5 patients with cerebral hyperperfusion syndrome regardless of the presence or absence of new lesions on MR images. In addition, postoperative cognitive impairment developed in 5 (45%) of 11 patients with asymptomatic cerebral hyperperfusion on CBF imaging despite the absence of new lesions on any postoperative MR images. CONCLUSIONS Although cerebral hyperperfusion syndrome after CEA sometimes results in reversible brain edema visible on MR imaging, postoperative cerebral hyperperfusion -- even when asymptomatic -- often results in impaired cognitive function without structural brain damage on MR imaging.

Preoperative Cerebral Hemodynamic Impairment and Reactive Oxygen Species Produced During Carotid Endarterectomy Correlate With Development of Postoperative Cerebral Hyperperfusion

Background and Purpose— The purpose of the present study was to determine whether preoperative cerebral hemodynamic impairment and reactive oxygen species produced during carotid endarterectomy (CEA) correlate with development of postoperative cerebral hyperperfusion. Methods— Concentrations of malondialdehyde-modified low-density lipoprotein (MDA-LDL), a biochemical marker of oxidative damage, were measured in serum samples obtained from 90 patients undergoing CEA for ipsilateral ICA stenosis (>70%). Serum samples were obtained from a venous catheter inserted into the ipsilateral jugular bulb before clamping of the internal carotid artery (ICA), 10 minutes after clamping of the ICA, and 5 and 20 minutes after declamping of the ICA. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were also measured using single-photon emission computed-tomography before CEA. In addition, CBF was measured postoperatively. Results— Hyperperfusion (CBF increase >100% compared with preoperative values) was observed immediately after CEA in 12 patients (13%). Logistic regression analysis demonstrated that reduced preoperative CVR (95% CIs, 1.053 to 1.453; P=0.0097) and an increase in MDA-LDL (calculated as a percentage of the preclamp values) after ICA declamping (95% CIs, 0.862 to 0.980; P=0.0098) were significantly associated with development of postoperative cerebral hyperperfusion among the variables tested. Ten of 11 patients with reduced preoperative CVR and increased MDA-LDL after ICA declamping developed post-CEA hyperperfusion, and 2 of these patients developed cerebral hyperperfusion syndrome. Conclusions— Both preoperative cerebral hemodynamic impairment and reactive oxygen species produced during surgery correlate with development of cerebral hyperperfusion after CEA.

Postcarotid endarterectomy improvement in cognition is associated with resolution of crossed cerebellar hypoperfusion and increase in 123I-iomazenil uptake in the cerebral cortex: a SPECT study.

Background: The purpose of the present study was to investigate whether resolution of crossed cerebellar hypoperfusion (CCH) and increase in 123I-iomazenil (IMZ) uptake in the ipsilateral cerebral cortex after carotid endarterectomy (CEA) are associated with postoperative improvement of cognitive function. Methods: Neuropsychological testing was performed preoperatively and after 1 postoperative month in 79 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≧70%). Brain perfusion single photon emission computed tomography (SPECT) using N-isopropyl-p-123I-iodoamphetamine and 123I-IMZ SPECT were also performed before and after surgery. Data were analyzed using a three-dimensional stereotaxic region of interest template. Results: Seven patients (9%) showed improvement in postoperative cognitive function. All the 7 patients exhibited both postoperative increase in blood flow in the ipsilateral cerebral cortex and resolution of CCH. Five patients (6%) had a postoperative hemispheric increase in 123I-IMZ uptake, and cognitive function improved in all of these 5 patients. Analysis by a receiver operating characteristic (ROC) curve was used to estimate the ability to discriminate between patients with and without postoperative cognitive improvement. The area under the ROC curve was significantly greater when analyzing the magnitude of postoperative resolution of CCH (0.991; 95% CI 0.984–1.001) or postoperative hemispheric increase in 123I-IMZ uptake (0.981; 95% CI 0.972–0.999) when compared with the magnitude of postoperative increase in cerebral blood flow (0.929; 95% CI 0.886–0.971) (p < 0.05). Conclusions: Resolution of CCH and increase in 123I-IMZ uptake in the ipsilateral cerebral cortex after CEA is associated with postoperative improvement in cognitive function. These results may indicate that cognitive impairment is related to a state of potentially reversible central benzodiazepine receptor downregulation in the cortex in response to transient ischemic attack or minor stroke.

Intraoperative Microemboli and Low Middle Cerebral Artery Blood Flow Velocity Are Additive in Predicting Development of Cerebral Ischemic Events After Carotid Endarterectomy

Background and Purpose— Microemboli generated during dissection of the carotid arteries in patients undergoing carotid endarterectomy result in postoperative cerebral ischemic events. The purpose of this study was to determine whether these events correlate with middle cerebral artery blood flow velocity. Methods— One hundred sixty-three patients with ipsilateral internal carotid artery stenosis (>70%) underwent carotid endarterectomy under transcranial Doppler monitoring of mean blood flow velocity and microembolic signals in the ipsilateral middle cerebral artery. Results— Logistic regression analysis of several variables demonstrated that only middle cerebral artery mean blood flow velocity during carotid dissection was significantly associated with new postoperative neurological deficits in patients with microembolic signals during carotid dissection (95% CI, 1.069 to 1.528; P=0.0072). The combination of low middle cerebral artery mean blood flow velocity (≤28 cm/s) and microembolic signals ≥10 during carotid dissection resulted in improved specificity and positive predictive value for the development of new postoperative neurological deficits when compared with either criterion used alone. Conclusions— Intraoperative microemboli and low middle cerebral artery mean blood flow velocity are additive in predicting the development of cerebral ischemic events after carotid endarterectomy.

Significance of postoperative crossed cerebellar hypoperfusion in patients with cerebral hyperperfusion following carotid endarterectomy: SPECT study

PurposeCerebral hyperperfusion after carotid endarterectomy (CEA) results in cerebral hyperperfusion syndrome and cognitive impairment. The goal of the present study was to clarify the clinical significance of postoperative crossed cerebellar hypoperfusion (CCH) in patients with cerebral hyperperfusion after CEA by assessing brain perfusion with single-photon emission computed tomography (SPECT).MethodsBrain perfusion was quantitatively measured using SPECT and the [123I]N-isopropyl-p-iodoamphetamine-autoradiography method before and immediately after CEA and on the third postoperative day in 80 patients with ipsilateral internal carotid artery stenosis (≥70%). Postoperative CCH was determined by differences between asymmetry of perfusion in bilateral cerebellar hemispheres before and after CEA. Neuropsychological testing was also performed preoperatively and at the first postoperative month.ResultsEleven patients developed cerebral hyperperfusion (cerebral blood flow increase of ≥100% compared with preoperative values) on SPECT imaging performed immediately after CEA. In seven of these patients, CCH was observed on the third postoperative day. All three patients with hyperperfusion syndrome exhibited cerebral hyperperfusion and CCH on the third postoperative day and developed postoperative cognitive impairment. Of the eight patients with asymptomatic hyperperfusion, four exhibited CCH despite resolution of cerebral hyperperfusion on the third postoperative day, and three of these patients experienced postoperative cognitive impairment. In contrast, four patients without postoperative CCH did not experience postoperative cognitive impairment.ConclusionsThe presence of postoperative CCH with concomitant cerebral hyperperfusion reflects the development of hyperperfusion syndrome. Further, the presence of postoperative CCH in patients with cerebral hyperperfusion following CEA suggests development of postoperative cognitive impairment, even when asymptomatic.

Concentration of Matrix Metalloproteinase-9 in the Jugular Bulb during Carotid Endarterectomy Correlates with Severity of Intraoperative Cerebral Ischemia

Background: Matrix metalloproteinase (MMP)-9 targets major components of the basal lamina of cerebral blood vessels and is a biochemical marker of blood-brain barrier disruption. The goal of this study was to determine whether plasma concentrations of MMP-9 in the jugular bulb during carotid endarterectomy (CEA) correlate with severity of intraoperative cerebral ischemia. Methods:In 41 patients undergoing CEA for ipsilateral internal carotid artery (ICA) stenosis, plasma samples for measurement of MMP-9 concentration were intraoperatively obtained from a venous catheter inserted into the ipsilateral jugular bulb. Transcranial cerebral oxygen saturation using near-infrared spectroscopy was also monitored intraoperatively to assess the severity of the ischemic insult during ICA clamping. Results: The MMP-9 concentrations were significantly higher after ICA declamping than before ICA clamping (p = 0.0023). A strong linear correlation was observed between the severity of the ischemic insult during carotid clamping and the increase in MMP-9 levels after ICA declamping (r = 0.776; p < 0.0001). At the postoperative neurological assessment, 3 patients showed transient minor neurological deficits. The MMP-9 level in the jugular bulb after ICA declamping was increased in patients with postoperative transient neurological deficits relative to those without. Conclusions: The concentration of MMP-9 in the jugular bulb during CEA correlates with the severity of intraoperative cerebral ischemia.

Early post-ischemic hyperemia on transcranial cerebral oxygen saturation monitoring in carotid endarterectomy is associated with severity of cerebral ischemic insult during carotid artery clamping.

Abstract Background and objective: In animal models, the magnitude of early post-ischemic hyperemia tends to correlate with the duration and intensity of prior ischemic insult. The aim of this study was to determine whether early post-ischemic hyperemia in human brain during carotid endarterectomy (CEA) is associated with the severity of cerebral ischemic insult during clamping of the internal carotid artery (ICA). Methods: Transcranial cerebral oxygen saturation using near-infrared spectroscopy was monitored intraoperatively in 171 patients undergoing CEA for ipsilateral ICA stenosis (>70%) to assess the intensity of cerebral hemispheric ischemia during ICA clamping and the magnitude of early post-ischemic hyperemia after ICA declamping. Results: Early post-ischemic hyperemia peaked within 3 minutes after ICA declamping and resolved at 20 minutes after ICA declamping. A significant correlation was observed between the magnitude of early post-ischemic hyperemia and the intensity of cerebral ischemia (r=0.697; p<0.0001). Eight patients recovered from anesthesia with a new minor neurological deficit on the side contralateral to the CEA (4.7%). Analysis by receiver operating characteristics (ROC) curve was used to estimate the ability to discriminate between patients with and without post-operative development of new neurological deficits. Area under the ROC curve was significantly greater when analysing the magnitude of early post-ischemic hyperemia (1.00; 95% CI: 0.99–1.00) when compared with the intensity of cerebral ischemia (0.93; 95% CI: 0.89–0.98) (p<0.01). Conclusion: Early post-ischemic hyperemia in CEA is correlated with the severity of cerebral ischemic insult during clamping of the ICA.

Contents Vol. 25, 2008

S 13th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics and 5th National Congress of the Italian Society of Neurosonology and Cerebral Hemodynamics Genova, Italy, May 10–13, 2008 Editors: M. Del Sette (Genova); C. Gandolfo (Genova); K. Niederkorn (Graz); D. Russell (Oslo)