Joseph Zurica

Neuropsychological dysfunction in the absence of structural evidence for cerebral ischemia after uncomplicated carotid endarterectomy.

OBJECTIVE: Neurocognitive dysfunction has been shown to occur in roughly 25% of patients undergoing carotid endarterectomy (CEA). Despite this, little is known about the mechanism of this injury. Recently, several groups have shown that new diffusion weighted imaging (DWI)-positive lesions are seen in 20% of patients undergoing CEA. We investigated to what degree neurocognitive dysfunction was associated with new DWI lesions. METHODS: Thirty-four consecutive patients undergoing CEA were subjected to pre- and postoperative cognitive evaluation with a battery of neuropsychological tests. Postoperative magnetic resonance imaging was performed in all patients within 24 hours of surgery. Lesions that showed high signal on DWI and restricted diffusion on apparent diffusion coefficient maps but no abnormal high signal on the fluid-attenuated inversion recovery images were considered hyperacute. RESULTS: Cognitive dysfunction was seen in eight (24%) patients. New hyperacute DWI lesions were seen in three (9%). Only one (13%) of the patients with cognitive dysfunction had a new DWI lesion. Two thirds of the new DWI lesions occurred in the absence of cognitive deterioration. Patients with cognitive dysfunction had significantly longer carotid cross-clamp times. CONCLUSION: Neurocognitive dysfunction after CEA does not seem to be associated with new DWI positive lesions.

Comparison of Electrophysiologic Monitors With Clinical Assessment of Level of Sedation

OBJECTIVE To assess the correlation between 2 clinical sedation scales and 2 electroencephalographic (EEG)-based monitors used during surgical procedures that required mild to moderate sedation. PATIENTS AND METHODS Patients scheduled for elective surgery participated in this Institutional review board-approved study from March 2003 to February 2004. Level of sedation was determined both clinically using the Ramsay and the Observers Assessment of Alertness/Sedation scales and with 2 EEG measures (the Bispectral Index version XP [BIS XP] or the Patient State Analyzer [PSA 4000]). Correlation between these 2 measures of sedation were tested using nonparametric statistical tests. RESULTS The BIS XP monitor was used in 26 patients, and the PSA 4000 monitor was used in 24 patients. The Ramsay and Observers Assessment of Alertness/Sedation scores correlated with each other (r = -0.96; P < .001) and with both the BIS XP (r = -0.89 and r = 0.91, respectively; P < .001) and the PSA 4000 (r = -0.80 and r = 0.80, respectively; P < .001) values. However, this correlation was strongest only at the extremes. Between the BIS XP and PSA 4000 values of 61 and 80, the clinical sedation scores varied greatly. CONCLUSION On the basis of our results, these EEG-based monitors cannot reliably distinguish between light and deep sedation.

Predictors of neurocognitive decline after carotid endarterectomy

OBJECTIVE:Although the incidence of stroke after carotid endarterectomy (CEA) is low (1–3%), approximately 25% of patients experience subtle declines in postoperative neuropsychometric function. No studies have investigated the risk factors for this neurocognitive change. We sought to identify predictors of postoperative neurocognitive dysfunction. METHODS:We enrolled 186 CEA patients, with both symptomatic and asymptomatic stenosis, to undergo a battery of neuropsychometric tests preoperatively and on postoperative Days 1 and 30. Neurocognitive dysfunction was defined as a two standard deviation decline in performance compared with a similarly aged control group of lumbar laminectomy patients. Univariate logistic regression was performed for age, sex, obesity, smoking, symptomatology, diabetes mellitus, hypertension, hypercholesterolemia, use of statin medication, previous myocardial infarction, previous CEA, operative side, duration of surgery, duration of carotid cross-clamp, and weight-adjusted doses of midazolam and fentanyl. Variables achieving univariate P < 0.10 were included in a multivariate analysis. Data is presented as (odds ratio, 95% confidence interval, P-value). RESULTS:Eighteen and 9% of CEA patients were injured on postoperative Days 1 and 30, respectively. Advanced age predicted neurocognitive dysfunction on Days 1 and 30 (1.93 per decade, 1.15–3.25, 0.01; and 2.57 per decade, 1.01–6.51, 0.049, respectively). Additionally, diabetes independently predicted injury on Day 30 (4.26, 1.15–15.79, 0.03). CONCLUSIONS:Advanced age and diabetes predispose to neurocognitive dysfunction after CEA. These results are consistent with risk factors for neurocognitive dysfunction after coronary bypass and major stroke after CEA, supporting an underlying ischemic pathophysiology. Further work is necessary to determine the role these neurocognitive deficits may play in appropriately selecting patients for CEA.

APOE-ε4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy

Background: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-ε4 allele has been associated with worse outcome following stroke. Objective: To investigate the ability of APOE-ε4 to predict post-CEA neurocognitive dysfunction. Methods: Seventy-five patients with CEA undergoing elective CEA were prospectively recruited in this nested cohort study and demographic variables were recorded. Patients were evaluated before and 1 month after surgery with a standard battery of five neuropsychological tests. APOE genotyping was performed by restriction fragment length polymorphism analysis in all patients. Neuropsychological deficits were identified by comparing changes (before to 1 month post-operation) in individual performance on the test battery. Logistic regression was performed for APOE-ε4 and previously identified risk factors. Results: Twelve of 75 (16%) CEA patients possessed the APOE-ε4 allele. Eight of 75 (11%) patients experienced neurocognitive dysfunction on postoperative day 30. One month post-CEA, APOE-ε4–positive patients were more likely to be cognitively injured (42%) than APOE-ε4–negative patients (5%) (p = 0.002). In multivariate analysis, the presence of the APOE-ε4 allele increased the risk of neurocognitive dysfunction at 1 month 62-fold (62.28, 3.15 to 1229, p = 0.007). Diabetes (51.42, 1.94 to 1363, p = 0.02), and obesity (24.43, 1.41 to 422.9, p = 0.03) also predisposed to injury. Conclusion: The APOE-ε4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.

Post-carotid endarterectomy neurocognitive decline is associated with cerebral blood flow asymmetry on post-operative magnetic resonance perfusion brain scans

Abstract Objective: Up to 25% of patients experience subtle declines in post-operative neurocognitive function following, otherwise uncomplicated, carotid endarterectomy (CEA). We sought to determine if post-CEA neurocognitive deficits are associated with cerebral blood flow (CBF) abnormalities on post-operative MR perfusion brain scans. Methods: We enrolled 22 CEA patients to undergo a battery of neuropsychometric tests pre-operatively and on post-operative day 1 (POD 1). Neurocognitive dysfunction was defined as a two standard deviation decline in performance in comparison to a similarly aged control group of lumbar laminectomy patients. All patients received MR perfusion brain scans on POD 1 that were analysed for asymmetries in CBF distribution. One patient experienced a transient ischemic attack within 24 hours before the procedure and was excluded from our analysis. Results: Twenty-nine percent of CEA patients demonstrated neurocognitive dysfunction on POD 1. One hundred percent of those patients with cognitive deficits demonstrated CBF asymmetry, in contrast to only 27% of those patients without cognitive impairment. Post-CEA cognitive dysfunction was significantly associated with CBF abnormalities (RR=3.75, 95% CI: 1.62–8.67, p=0.004). Conclusion: Post-CEA neurocognitive dysfunction is significantly associated with post-operative CBF asymmetry. These results support the hypothesis that post-CEA cognitive impairment is caused by cerebral hemodynamic changes. Further work exploring the relationship between CBF and post-CEA cognitive dysfunction is needed.

A study of cognitive dysfunction in patients having carotid endarterectomy performed with regional anesthesia.

BACKGROUND: In previous studies, we found that approximately 25% of patients having carotid endarterectomy with general anesthesia (CEA general) develop cognitive dysfunction compared with a surgical control Group 1 day and 1 mo after surgery. In this study, we tested the hypothesis that patients having CEA with regional anesthesia (CEA regional) will develop significant cognitive dysfunction 1 day after surgery compared with a control group of patients receiving sedation 1 day after surgery. We did not study persistence of dysfunction. METHODS: To test this hypothesis, we enrolled 60 patients in a prospective study. CEA regional was performed with superficial and deep cervical plexus blocks in 41 patients. The control group consisted of 19 patients having coronary angiography or coronary artery stenting performed with sedation. A control group is necessary to account for the “practice effect” associated with repeated cognitive testing. The patients from the CEA regional group were enrolled at New York Medical Center and the control group at Columbia-Presbyterian Medical Center. The cognitive performance of all patients was evaluated using a previously validated battery of neuropsychometric tests. Differences in performance, 1 day after compared with before surgery, were evaluated by both event-rate and group-rate analyses. RESULTS: On postoperative day 1, 24.4% of patients undergoing CEA regional had significant cognitive dysfunction, where “significant” was defined as a total deficit score ≥2 SD worse than the mean performance in the control group. CONCLUSIONS: Patients undergoing CEA regional had an incidence of cognitive dysfunction which was not different than patients having CEA general as previously published and compared with a contemporaneously enrolled group.

Intraoperative magnesium infusion during carotid endarterectomy: a double-blind placebo-controlled trial.

OBJECT Recent data from both experimental and clinical studies have supported the use of intravenous magnesium as a potential therapy in the setting of cerebral ischemia. This study assessed whether intraoperative magnesium therapy improves neuropsychometric testing (NPT) following carotid endarterectomy (CEA). METHODS One hundred eight patients undergoing CEA were randomly assigned to receive placebo infusion or 1 of 3 magnesium-dosing protocols. Neuropsychometric testing was performed 1 day after surgery and compared with baseline performance. Assessment was also performed on a set of 35 patients concurrently undergoing lumbar laminectomy to serve as a control group for NPT. A forward stepwise logistic regression analysis was performed to evaluate the impact of magnesium therapy on NPT. A subgroup analysis was then performed, analyzing the impact of each intraoperative dose on NPT. RESULTS Patients treated with intravenous magnesium infusion demonstrated less postoperative neurocognitive impairment than those treated with placebo (OR 0.27, 95% CI 0.10-0.74, p = 0.01). When stratified according to dosing bolus and intraoperative magnesium level, those who were treated with low-dose magnesium had less cognitive decline than those treated with placebo (OR 0.09, 95% CI 0.02-0.50, p < 0.01). Those in the high-dose magnesium group demonstrated no difference from the placebo-treated group. CONCLUSIONS Low-dose intraoperative magnesium therapy protects against neurocognitive decline following CEA.

High dose magnesium infusions are not associated with increased pressor requirements after carotid endarterectomy.

INTRODUCTION:Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of α-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy. METHODS:Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups. RESULTS:All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P < 0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered. CONCLUSION:There were no significant differences detected in the 1) percentage of patients requiring pressor support, 2) the duration of postoperative pressor support, or 3) the amount of phenylephrine support needed between controls and magnesium treated patients. The percentage of patients requiring pressure support depended on the minimum systolic blood pressure ordered after surgery.

A novel quantification method for determining previously undetected silent infarcts on MR-perfusion in patients following carotid endarterectomy

The purpose of this paper is to evaluate the post-operative Magnetic Resonance Perfusion (MRP) scans of patients undergoing carotid endarterectomy (CEA), using a novel image-analysis algorithm, to determine if post-operative neurocognitive decline is associated with cerebral blood flow changes. CEA procedure reduces the risk of stroke in appropriately selected patients with significant carotid artery stenosis. However, 25% of patients experience subtle cognitive deficits after CEA compared to a control group. It was hypothesized that abnormalities in cerebral blood flow (CBF) are responsible for these cognitive deficits. A novel algorithm for analyzing MR-perfusion (MRP) scans to identify and quantify the amount of CBF asymmetry in each hemisphere was developed and to quantify the degree of relative difference between three corresponding vascular regions in the ipsilateral and contralateral hemispheres, the Relative Difference Map (RDM). Patients undergoing CEA and spine surgery (controls) were examined preoperatively, and one day postoperatively with a battery of neuropsychometric (NPM) tests, and labeled “injured” patients with significant cognitive deficits, and “normal” if they demonstrated no decline in neurocognitive function. There are apparently significant RDM differences with MRP scans between the two hemispheres in patients with cognitive deficits which can be used to guide expert reviews of the imagery. The proposed methodology aids in the analysis of MRP parameters in patients with cognitive impairment.