OBJECTIVE Distal cerebral embolization is a known complication of carotid interventions. Here we prospectively investigate whether subclinical microembolization seen on post-operative MRI leads to cognitive deficits in a cohort of patients undergoing carotid revascularization procedures. METHODS Patients undergoing carotid interventions and eligible for MRI scanning were recruited to participate. Among 247 patients who received both preoperative and postoperative MRI evaluations, a total of 51 patients also completed neuropsychological testing prior to and at one month following the procedures. Cognitive evaluation included the Rey Auditory Verbal Learning Test (RAVLT) for memory evaluation and the Mini-Mental State Examination (MMSE) for general cognitive impairment screening. RESULTS All 51 patients (16 CAS and 35 CEA) were male with a mean age of 71 years, ranging 54 to 89 years. Among them, 27 patients (53%) were symptomatic preoperatively including 11 patients who had prior stroke and 16 patients who had prior TIA. The majority of the patients had significant medical comorbidities including hypertension (96%), diabetes (31.3%), coronary artery disease (47%), and COPD (15.7%). Two patients (4%) had prior ipsilateral CEA and 8 had contralateral carotid occlusion (15.7%). Memory decline evident on RAVLT was identified in 21 patients including 8 CAS patients and 13 CEA patients. Eleven patients had evidence of procedure-related microemboli. Although there was no significant difference in baseline cognitive function or memory change between CEA and CAS cohort, the CAS cohort had significantly higher incidence of microembolic lesions. Multivariate regression analysis showed that procedure-related microembolization was associated with memory decline (P=0.016) as evident by change in RAVLT. Prior history of neurologic symptom was significantly associated with poor baseline cognitive function (MMSE) (P=0.03) and overall cognitive deterioration (change in MMSE) (P=0.026) as determined by Wilcoxon Rank Sum test and linear regression analysis respectively. CONCLUSIONS Although both CEA and CAS are effective in stroke prevention with minimal neurologic complication, neurocognitive effects remain uncertain. Procedure-associated microembolization and pre-existing neurologic symptoms are associated with poor baseline cognitive function and memory decline following the procedures. Further comprehensive cognitive evaluation to determine the benefit of carotid interventions is warranted.

OBJECTIVE Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts. METHODS 119 patients including 46% symptomatic patients who underwent carotid revascularization were recruited. Neuropsychological testing was administered preoperatively and at 1, 6, and 12 months postoperatively. Rey Auditory Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effort. All patients also received 3T brain MRIs with a diffusion-weighted sequence (DWI) preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures. RESULTS A total 587 DWI lesions were identified on 3T MRI in 81.7% of CAS and 36.4% of CEA patients with a total volume of 29327mm3. Among them, 54 DWI lesions were found in CEA patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarct (OR: 6.6 [2.1–20.4], p<.01) and infarct volume (P=.004). Diabetes and contralateral carotid severe stenosis/occlusion had a trend of positive association with infarct volume, while systolic blood pressure more or equal to 140mmHg had a negative association (P=.1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall following carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short and long-term RAVLT changes (P<0.05). CONCLUSIONS Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlates with long-term cognitive changes, suggesting that micro-embolization should be considered as a surrogate measure for carotid disease management.

Background and aims Resistin has been associated with atherosclerotic inflammation and cardiovascular complications. We and others have previously shown that PKC-epsilon (PKCε) is involved in resistin-induced smooth muscle cell (VSMC) dysfunction at a high pathological concentration. This study aimed to evaluate the role and potential pathways of resistin at a physiological concentration, in atherosclerosis-related inflammation. Methods Plasma from patients with atherosclerosis was analyzed for resistin concentration. Patients were divided into tertiles based on resistin levels and cytokines were compared between tertiles. Macrophages were then treated with resistin in the presence or absence of PKCε inhibitor and/or TLR4 blocking-antibody, and their inflammatory state was evaluated with ELISA, RT-PCR, immunocytochemistry, and Western blot. Results We observed significant associations between plasma resistin levels and TNF-α, IL-6, IL-12, MIP-1α, MIP-1β, and CD40L. Our in vitro analyses revealed that resistin activated PKCε via TLR4. This was followed by NF-kB activation and induction of a pro-inflammatory phenotype in macrophages, significantly upregulating CD40, downregulating CD206 and stimulating gene expression and secretion of the inflammatory cytokines, for which we found association in our plasma analysis. Resistin also induced persistent TRAM and CD40L upregulation up to 36 hours after resistin treatment. PKCε and TLR4 inhibitors suppressed gene expression to levels similar to control, especially when used in combination. Conclusions Resistin, at a physiological concentration, exacerbates the inflammatory response of macrophages. PKCε is a key upstream mediator in resistin-induced inflammation that may interact synergistically with TLR4 to promote NF-kB activation, while TRAM is an important signal. PKCε and TRAM may represent novel molecular targets for resistin-associated chronic atherosclerotic inflammation.

This is the largest prospective study evaluating SPY technology in peripheral vascular interventions. Our study shows that SPY is a valuable tool in visualizing real-time procedural outcomes and providing additionally useful information on regional tissue perfusion. Further investigation is warranted to standardize outpatient use and to determine threshold values that predict wound healing.

OBJECTIVE Carotid interventions are important in helping to reduce the risk of stroke for patients with high-grade carotid artery stenosis; however, incidence of subclinical cerebral microemboli can occur during these procedures. Previously, associations have been found between incidence of microemboli and postoperative decline in memory. We therefore sought to determine whether this decline persisted long-term and to assess changes in other cognitive domains. METHODS Patients were prospectively recruited under an IRB-approved protocol at a single academic center. Neuropsychological testing was administered preoperatively and at 1 month and 6 month intervals postoperatively. Cognitive domains that were evaluated included verbal memory, visual memory, psychomotor speed, dexterity, and executive function. Diffusion weighted MRI (DWI) sequencing was performed preoperatively and within 48 hours postoperatively to identify procedure-related microemboli. Univariate and multivariate regression models were used to identify relationships between microembolization, demographics, and cognition. RESULTS 80 patients were included; all were male and average age was 69 years. Forty patients underwent CAS and 40 CEA. 45% were diabetic, 50% had CAD, and 41% had prior neurologic symptoms. 45 (56%) of the patients had new postoperative microemboli. Microembolization was significantly more common in the CAS cohort (P<.005). Univariate analysis demonstrated that patients with procedure-related embolization showed decline 1 month postoperatively in verbal memory and Trail Making A measures. Multivariate analysis demonstrated that procedure-related embolization (OR: 2.8, P=.04) and pre-op symptomatic stenosis (OR: 3.2, P=.026) were independently predictors of decline for the RAVLT Short Delay measure at 1 month; however, at 6 months there was no significant relationship between emboli and decline on RAVLT Short Delay, while age (OR: 1.1, P=.005) and COPD (OR: 7.1, P=.018) were significantly associated with decline at 6 months following intervention. CONCLUSIONS Microembolization that is associated with carotid artery intervention predicts short-term cognitive decline. However, some of these cognitive deficits persist at 6 months following intervention, and further investigation is warranted to determine individual patient risk factors that may impact recovery.