High-grade Internal Carotid Artery Stenosis Research Articles

MR Angiography at 3 Tesla to Assess Proximal Internal Carotid Artery Stenoses: Contrast-Enhanced or 3D Time-of-Flight MR Angiography?

The aim of this study was to compare the diagnostic accuracy of 3D time-of-flight (TOF-MRA) and contrast-enhanced (CE-MRA) magnetic resonance angiography at 3T for detection and quantification of proximal high-grade stenosis using multidetector computed tomography angiography (MDCTA) as reference standard. The institutional ethics committee approved this prospective study. A total of 41 patients suspected of having internal carotid artery (ICA) stenosis underwent both MDCTA and MRA. CE-MRA and TOF-MRA were performed using a 3.0-T imager with a dedicated eight-element cervical coil. ICA stenoses were measured according to the North American Symptomatic Carotid Endarterectomy Trial criteria and categorized as 0-25 % (minimal), 25-50 % (mild), 50-69 % (moderate), 70-99 % (high grade), and 100 % (occlusion). Sensitivity and specificity for the detection of high-grade ICA stenoses (70-99 %) and ICA occlusions were determined. In addition, intermodality agreement was assessed with κ-statistics for detection of high-grade ICA stenoses (70-99 %) and ICA occlusions. A total of 80 carotid arteries of 41 patients were reviewed. Two previously stented ICAs were excluded from analysis. On MDCTA, 7 ICAs were occluded, 12 ICAs presented with and 63 without a high-grade ICA stenosis (70-99 %). For detecting 70-99 % stenosis, both 3D TOF-MRA and CE-MRA were 91.7 % sensitive and 98.5 % specific, respectively. Both MRA techniques were highly sensitive (100 %), and specific (CE-MRA, 100 %; TOF-MRA, 98.7 %) for the detection of ICA occlusion. However, TOF-MRA misclassified one high-grade stenosis as occlusion. Intermodality agreement for detection of 70-99 % ICA stenoses was excellent between TOF-MRA and CE-MRA [κ = 0.902, 95 % confidence interval (CI) = 0.769-1.000], TOF-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000), and CE-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000). Both 3D TOF-MRA and CE-MRA at 3T are reliable tools for detecting high-grade proximal ICA stenoses (70-99 %). 3D TOF-MRA might misclassify pseudo-occlusions as complete occlusions. If there are no contraindications for CE-MRA, CE-MRA is recommended as primary MR imaging modality.

Wall shear stress distribution at the carotid bifurcation: influence of eversion carotid endarterectomy

To test the feasibility of four-dimensional (4D) flow MRI to quantify the systolic wall shear stress (WSSsystole) and oscillatory shear index (OSI) in high-grade internal carotid artery (ICA) stenosis before and after endarterectomy (CEA). Twenty patients with ≥60 % ICA stenosis were prospectively and consequently included. Four-dimensional flow MRI was used to measure individual time-resolved 3D blood flow velocities. Segmental WSSsystole and OSI were derived at eight wall segments in analysis planes positioned along the ICA, common (CCA) and external carotid artery (ECA). Regional WSSsystole of all patients decreased after CEA (P < 0.05). Changes were most prominent at the ICA bulb but remained unchanged in the CCA and ECA. OSI was significantly lower after CEA in the lateral vessel walls (P < 0.05). For analysis planes at the stenosis in- and outlet, a reduction of mean WSSsystole by 32 % and 52 % (P < 0.001) and OSI distal to the stenosis (40 %, P = 0.01) was found after CEA. Our findings show the potential of in vivo 4D flow MRI to quantify haemodynamic changes in wall shear stress even in patients with complex flow conditions.

Abstract TP139: Usefulness of Staged Angioplasty for Carotid Artery Stenting

Introduction: Hyperperfusion syndrome is one of the most serious complications after carotid revascularization. We report the efficacy of staged angioplasty (SAP) for patients with severely impaired cerebral vasoreactivity. Methods: From April 2008 to March 2012, seventeen of 83 patients with high-grade internal carotid artery stenosis were considered at high risk of postoperative hyperperfusion based on the results of preoperative single-photon emission computed tomography (SPECT) with acetazolamide. They were treated with SAP which consists of mild balloon angioplasty (1st stage) and carotid artery stenting one month later (2nd stage). Rest 123I-IMP SPECT was performed to evaluate hyperperfusion just after the procedure of each stage. Results: Before we induced SAP procedure, 1.9%(3 of 158) of patients treated with CAS had a hemorrhagic complication due to hyperperfusion. None of 17 patients treated with SAP had hyperperfusion phenomenon on SPECT, and a hemorrhagic complication. The mean rate of stenosis was 91% before treatment, 70% after 1st stage, 21% after 2nd stage. Although stenosis had been worsened during the period between 1st and 2nd stages in four patients, all patients showed satisfactory recovery of cerebral blood flow after 2nd stage. Conclusions: In selected patients, SAP is effective and relatively safe to decrease hyperperfusion syndrome after procedures. However, method to choose high-risk patient for postoperative hyperperfusion and protocol of treatment are still controversial.

Abstract TP168: Angiography-Like Grading of Carotid Artery Stenosis with B-Flow Ultrasound: 3D-Ultrasound Supported Comparison with Computer Tomography Angiography Results in a High Accuracy

Background: Evaluation of various imaging modalities for grading internal carotid artery (ICA) stenosis can be performed by comparison of minimal lumen diameters (MLD) as well as percent ICA-stenosis calculated with a healthy distal reference segment (NASCET method). The two dimensional B-Flow (BF) ultrasound (US) imaging method displays stenoses in a similar fashion as reference methods like multi-slice CT-angiography (MS CTA) and in part like catheter angiography. Aim: to evaluate the accuracy of BF-US carotid stenosis grading at NASCET locations adjusted with 3D-color-Doppler ultrasound by comparison with MSCTA. Methods: Patients were screened by doppler US velocity criteria after informed consent. 3D-US was made for distance taking and search for anatomical markers. CTA were compared with BF-US in 91 ICA stenoses of 69 patients at identical projections of longitudinal sections. 58 low to high grade ICA stenoses were imaged by selective angiography and compared with CTA. Diameters of stenosed ICA were rendered coaxial on CTA. Angiography was made with AXIOM (Siemens, Germany), MSCTA with SOMATOM (Siemens, Germany); Ultrasound Logic 9 with 8 Mhz linear scanner for BF-US and a 10 Mhz 3D-US probe, GE, USA. All readings were by two independent observers for each technique. Quantitative angiography was done with MEDIS software (Netherlands), Bland-Altman analysis and statistics with SPSS (USA). Identical planes were finally confirmed by overlay technique of BF with 3D-US and CTA in addtition to the use of anatomical markers. Results: Degree of stenosis was slightly understimated by CTA compared with angiography with mean differences (±SD) of -0.4% (±6.1%) for longitudinal sections. In this cohort, discrimination of binary 50% NASCET stenosis with BF-US had a 90% sensitivity, 94% specifity and an accuracy of 91%; discrimination of binary 70% NASCET stenosis with BF-US had a sensitivity of 88%, specifity of 93% and an accuracy of 92%. Conclusion: diagnostic performance of CTA proved to be excellent compared with angiography and 3D-US adjusted BF-US measurements were highly accurate, when using corresponding projections. BF-US may be a valuable additional tool for screening and confirmation of CAS for therapeutic stratification.

Overexpression of microRNA-145 in atherosclerotic plaques from hypertensive patients

Background: MicroRNAs (miRNAs) are endogenous, non-coding, short, single-stranded RNAs and represent a new class of gene regulators. Recent evidence supports a role for miRNAs in cardiovascular pathophysiology and atherosclerosis development. We have previously demonstrated that miR-145 is widely expressed in human atherosclerotic lesions and its downregulation has been correlated with vascular smooth muscle cell dedifferentiation, a cardinal step in the development of atherosclerosis. However, no evidences are available at this time about modulation of miR-145 in the setting of hypertension. Thus, the aim of this study was to investigate the expression of miR-145 in complicated hypertension.Materials and methods: Atherosclerotic plaques were obtained from 22 patients undergoing carotid endarterectomy for high-grade internal carotid artery stenosis. Plaques were subdivided into hypertension (n = 15) and control (n = 7) groups according to the presence or absence of hypertension (as defined by blood pressure > 140/90 mmHg or current antihypertensive treatment). In study plaques, miR-145 values were evaluated using real-time PCR. The level of induction has been tested by using ΔΔ cycle threshold method.Results: We found that miR-145 was significantly more expressed in atherosclerotic plaques of hypertensive patients than in control plaques (1.201 ± 0.260 vs 0.483 ± 0.148 fold induction ± SE; p = 0.026). Moreover, a post-hoc analysis showed that treatment with angiotensin receptor blockers may be associated with the maximum increase in miR-145 levels, although these data did not show any statistical significance probably due to the limited sample size.Conclusions: To the best of our knowledge, this study is the first demonstration that hypertension may upregulate miR-145 expression in human atherosclerotic plaques. Future investigations will be necessary to establish the molecular readout of miR-145 upregulation in atherosclerotic lesions in hypertension.

Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion

Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk. We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model. Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99-7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method. CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.

Quantitative High-Field Diffusion Tensor Imaging of Cerebral White Matter in Asymptomatic High-Grade Internal Carotid Artery Stenosis

Background: Recently, several studies using diffusion-sensitized MRI reported changes in patients with high-grade internal carotid artery stenosis (ICAS) suggestive of subtle brain tissue damage. We used diffusion tensor imaging (DTI) to investigate the microstructural cerebral white matter integrity in asymptomatic patients with high-grade ICAS. Methods: In 15 asymptomatic patients with unilateral high grade (>70%) ICAS, we used 3T MRI including DTI. We used a region-of-interest approach comparing quantitative DTI metrics between both hemispheres including the so-called border zones. MR images were also assessed for periventricular white matter lesions (PWML) as well as collaterals via the circle of Willis. Results: There was no significant intraindividual difference of fractional anisotropy or mean diffusivity values between the hemispheres for any region. PWML was graded 0° in 6 patients, I° in 9 and II° in 2. Conclusions: In clinically asymptomatic patients with high-grade unilateral ICAS, there was no difference between the DTI parameters of the affected and the unaffected hemisphere. These findings contrast with other studies in asymptomatic high-grade ICAS, which is likely due to patient selection. These findings argue against concomitant chronic tissue integrity changes and implicate the benignity of asymptomatic carotid artery disease in individual patients.

Abstract 2633: Coated-Platelet Levels are Elevated in Symptomatic Carotid Stenosis Patients and Associated with Stroke Recurrence

Background: Coated-platelets are a subset of platelets with high procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels, expressed as percentages of the total platelet population, are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage compared to controls. Because of these findings, we investigated whether coated-platelets are elevated in patients with symptomatic carotid stenosis compared to controls and if there is an association between coated-platelet levels and stroke recurrence among subjects with carotid stenosis. Methods: Coated-platelet levels were determined in 40 consecutive patients with acute stroke due to ipsilateral high-grade internal carotid artery stenosis and 60 gender-frequency-matched controls without history of stroke. The neurologist establishing the diagnosis was unaware of the patient's coated-platelet levels, and the individuals performing the coated-platelet assay were not aware of the clinical diagnosis. Stroke recurrence data were obtained through stroke clinic visits or telephone interviews performed at 1month following the initial infarct. The distribution of baseline characteristics was compared between patients and controls using either a t-test for continuous measures or a Chi-square test (or Fisher’s exact test) for categorical measures. Linear regression models were fit to explore the association between carotid stenosis status and coated-platelet levels with and without adjustment for confounding factors. Percentages of subjects who developed a recurrent stroke at one month were compared using Fisher’s exact test. Results: Coated-platelet levels (mean±SD) were significantly higher in patients with symptomatic carotid stenosis compared to controls (41.3±15.5% vs. 30.1±13.4%, p=0.0002). The estimated difference remained significant after adjustment for demographics, medication use and co-morbidities (p=0.0003). Among the 40 carotid stenosis patients, the cumulative incidence of recurrent stroke at 1 month was 18% (95% CI:9-34%, 7 recurrences). Patients were then analyzed according to quartiles of coated-platelet levels (split at ≤32%, 32.1-42.4%, 42.5-51%, &gt;51%). The 1-month stroke recurrence percentages differed significantly between the coated-platelet quartiles (p=0.041), with 50% recurrence percentage (n=5) among patients in the highest quartile compared to 10% among those in the first (n=1) and third (n=1) quartiles and 0% among those in the second quartile. Conclusions: Coated-platelet levels are higher in patients with symptomatic high-grade carotid stenosis compared to controls and are associated with early stroke recurrence in this patient population. Additional study of coated-platelets in carotid stenosis is warranted.

Abstract 2912: Quantitative T2'-Imaging detects Increased Oxygen Extraction in High-Grade Internal Carotid and Middle Cerebral Artery Stenosis

Background and Purpose: Quantitative T2'-imaging (qT2') detects regional changes in the relation of oxygenated and deoxygenated hemoglobine (Hb) using their different signal characteristics in gradient echo imaging. In contrast to classical T2* imaging, T2’-imaging is corrected for spin-spin effects. Regional differences in Hb oxygenation might reflect areas with increased oxygen extraction for compensation of reduced perfusion pressure. The aim of the study was to investigate qT2’-imaging in perfusion-restricted areas in patients with high-grade stenoses of brain-supplying arteries. We hypothesized that T2’-values are lower in perfusion-restricted areas as compared to normal perfused tissue. Methods: 18 patients (15 men, 3 women; mean age 54 years, SD±12.8) with sonographic unilateral symptomatic or asymtpomatic high-grade extracranial ICA stenosis/occlusion (&gt;70%, NASCET criteria), or MR-angiographic proven unilateral high-grade (&gt;50%) intracranial ICA or proximal MCA stenosis/occlusion were included. Patients with significant bilateral stenoses were excluded. MRI comprised perfusion-weighted imaging and quantitative, motion corrected T2’-imaging. Time-to-peak (TTP)- and mean-transit-time (MTT)-maps were thresholded for different degrees of perfusion delays (e.g. &gt;0 sec, &gt;2 sec) in relation to the contralateral, healthy hemisphere. Mean T2’-values in perfusion-restricted areas were compared to T2'-values in corresponding contralateral or ipsilateral, normoperfused areas. Data are given as mean (+−SD). Results: Mean size of perfusion-restricted areas in TTP-maps (TTP-delay &gt;0 sec) was 10.8 ml (+−6.3) and 11.5 ml (+−6.2) in MTT-maps (MTT-delay &gt;0 sec) decreasing to 4.5 ml (+−4.7) in areas with a TTP-delay &gt;4 sec and 6.9 ml (+−5.5) in areas with a MTT-delay &gt;4 sec, respectively. T2'-values were significantly (p&lt;0.01) lower in all perfusion-restricted compared to corresponding contralateral brain areas: For TTP-delay &gt;0 sec, T2’-values were (ipsilateral) 115.2 ms (+−9) vs. (contralateral) 125.4 ms (+− 11.5). For MTT-delay &gt;0 sec T2’-values were (ipsilateral) 114.5 ms (+−9.1) vs. (contralateral) 127.7 ms (+− 9.5). Differences in T2’-values increased with the severity of the hypoperfusion. Ipsilateral T2’-values outside the perfusion-disturbed areas did not differ from contralateral T2’-values. Conclusions: Motion-corrected T2'-imaging detects areas with increased oxygen extraction within perfusion-restricted tissue in patients with high-grade occlusive vessel disease. T2’-imaging may add important information on the severity of the perfusion-disturbance with respect to its metabolic consequences. Its general suitability and its value for clinical decision making needs further evaluation as well as a thorough comparison with the current gold standard for the assessment of cerebral oxygen consumption, PET.

Abstract 3772: High Precision and Accuracy of B-flow Ultrasound Morphometry of Internal Carotid Artery Stenosis: Improved Non-invasive Stenosis Grading

Background: Evaluation of various imaging modalities for grading internal carotid artery (ICA) stenosis can be performed by comparison of minimal lumen diameters (MLD) as well as percent ICA-stenosis calculated with a healthy distal reference segment (NASCET method). The new B-Flow (BF) ultrasound (US) imaging method displays stenosis in a similar fashion as reference methods like catheter angiography (A) and multi-slice CT-angiography (MS CTA). Aim: to evaluate the accuracy of MSCTA by using multiplanar reformation (MPR) for measuring ICA stenosis compared with of A as well as accuracy and precision of BF-US compared with MSCTA at corresponding projections and locations. Methods and patients: CTA of ICA were compared with A in 37 low to high grade ICA stenoses of patients screened by doppler US velocity criteria. CTA were compared with US in 80 ICA stenoses of 63 patients in a similar fashion at identical projections. Diameters of stenosed ICA were rendered coaxial on CTA. A was made with AXIOM (Siemens, Germany), MSCTA with SOMATOM (Siemens, Germany); Ultrasound Logic 9 with 6-8 Mhz linear scanner, GE, USA. All readings were by two independent observers for each technique. Quantitative A was done with MEDIS software (Netherlands), Bland-Altman analysis and statistics with SPSS (Germany). Identical planes were confirmed by overlay technique. Results: MLD was slightly overestimated by CTA compared with angiography with mean differences (±SD) of 0.093 ± 0.25 mm for longitudinal sections. Pearson correlation coefficient (PCC) was 0.95. NASCET stenosis grade showed no bias between CTA and A (-0,5%±6.23% SD) and resulted in a PCC 0.93 for MPR's compared with A. MLD was slightly underestimated by parasaggital section (PSS) BF-US (0.031mm ± 0.23mm SD) compared with CTA, PCC = 0.96. NASCET ICA-stenoses were slightly underestimated by CTA, with mean differences of 1,16% ± 6,04% (SD), PCC was 0.92. In this cohort, discrimination of binary 50% NASCET stenosis with PSS BF-US had a 87%sensitivity, 86% specifity and an accuracy of 86%; discrimination of binary 70% NASCET stenosis with PSS BF-US had a sensitivity of 92%, specifity of 90% and an accuracy of 90%. Conclusion: diagnostic performance of CTA proved to be excellent compared with angiography and PSS 2D BF-US was highly accurate, when using corresponding projections. 2D BF-US may be a valuable additional tool for screening and confirmation of CAS for therapeutic stratification.

Functional assessment of high‐grade ICA stenosis with duplex ultrasound and transcranial Doppler

Background:Duplex ultrasound (DUS) has shown a >90% accuracy compared to angiography, concerning the degree of internal carotid artery (ICA) stenosis. However, uncertainty may occur in a severe stenosis, in which peak systolic velocity (PSV) may decrease owing to high flow resistance or high backward pressure. We investigated intracranial collateral flows using transcranial Doppler (TCD) to further evaluate the hemodynamic significance of high-grade ICA stenosis.Methods:In this retrospective study, 320 consecutive symptomatic patients were examined. The degree of ICA stenosis and collateral capacity in the circle of Willis was investigated by DUS and TCD. In addition, magnetic resonance angiography (MRA) was added in a subgroup of 204 patients. The criterion for hemodynamic significant ICA stenosis was established collateral flow.Results:In 91% of all symptomatic vessels (291 vessels), an ICA stenosis of ≥70% was found. Established collateral flow always indicated precerebral carotid artery disease of ≥70%. Furthermore, in 11% of the whole study material, collateral reserve capacity was found despite high-grade (≥70%) ICA stenosis. PSV in ICA <2·5 m s−1 was combined with established collateral flow and MRA stenosis of ≥70% in 9% (19 arterial systems). In 4%, doubt existed concerning the degree of stenosis after DUS.Conclusion:Transcranial Doppler helps to determine whether an ICA stenosis is of hemodynamic significance and to assess collateral patterns. Established collateral blood flow will help to identify patients with ≥70% (ECST) carotid artery disease. TCD might be of value when flow velocity criteria combined with plaque assessment by DUS are inclusive. Other diagnostic methods may also be considered.

Prevalence of Asymptomatic Carotid Artery Stenosis in the General Population: An Individual Participant Data Meta-Analysis

Conclusion: The prevalence of severe asymptomatic internal carotid artery (ICA) stenosis in the general population ranges from 0% to 3.1%. Summary: The authors sought to determine the prevalence of moderate and severe asymptomatic ICA stenosis using information from four population-based cohort studies. They used pooled cohort data to analyze prevalence of moderate and severe asymptomatic ICA stenosis by age and sex. This was an individual participant data meta-analysis of 23,706 participants from four population-based studies: the Malmo Diet and Cancer Study, Tromoso, Carotid Atherosclerosis Progression Study, and the Cardiovascular Health Study. Moderate asymptomatic ICA stenosis was defined as >50% to 69% stenosis. Severe stenosis was defined as >70% stenosis. Moderate asymptomatic ICA stenosis had a prevalence ranging from 0.2% (95% CI, 0.0%-0.4%) in men aged <50 years to 7.5% (95% CI, 5.2%-10.5%) in men aged ≥80 years. In women, prevalence of asymptomatic ICA stenosis ranged from 0% (95% CI, 0%-0.2%) to 5% (95% CI, 3.1%-7.5%). Severe asymptomatic ICA stenosis ranged from 0.1% to 3.1% (95% CI, 0.0%-0.3%) in men aged <50 years and from 1.7% to 5.3% in men aged >80. In women, the prevalence of severe asymptomatic ICA stenosis increases from 0% (95% CI, 0.0%-0.2%) in those aged <50 years to 0.9% (95% CI, 0.3%-2.4%) in those aged <80 years, respectively. Comment: Screening for asymptomatic ICA stenosis has not been endorsed by the US Preventative Health Services Task Force. There are no data here that will lead to a change in their opinion. Up to age 70 years, the prevalence of high-grade asymptomatic carotid stenosis is <2%. No comorbidity increases that prevalence beyond 2%. Given the relatively benign natural history of asymptomatic ICA stenosis, it seems highly unlikely from these data that screening for asymptomatic high-grade ICA stenosis can be clinically effective or cost-effective in any patient subgroup.

Downward Migration of Carotid Stent on 8 Months Follow-Up Imaging: Possible Stent “Watermelon- Seeding” Effect

One method used to treat atherosclerotic carotid disease is carotid artery stenting (CAS). A rarely encountered limitation of this technique is stent migration. Here, we present a rare case of carotid stent downward migration found on follow-up imaging 8 months post operation. A 70-year-old man presented with aphasia and right-sided weakness secondary to high-grade (99%) proximal left internal carotid artery (ICA) stenosis that was treated with CAS. Stent apposition distally was achieved as well as proximally at the carotid bulb without crossing the bifurcation and without going distally beyond the ICA angulation to avoid kinking. Eight months follow-up computerized axial angiogram showed downward migration of the stent into the common carotid with restenosis distal to the stent. A 6-8 × 40 mm stent was deployed and the stenosed area restented with good results to overlap with the older stent and landed distal to the ICA angulation. Interventionalists should be aware of the rare possibility of migrating downward "watermelon-seeding" of carotid stents. This report may generate the hypothesis that the stent watermelon-seeding effect may be related to proximal placement of a short stent below the ICA angulation and at the carotid bulb in severely stenotic lesion.

Cerebral Infarct in Patients with Bilateral High-Grade Internal Carotid Artery Stenosis: Analysis by Diffusion-Weighted Imaging

Background: Bilateral high-grade internal carotid artery (ICA) stenosis is critical for brain perfusion, and mechanisms of cerebral infarct induced by bilateral high-grade ICA stenosis can be investigated by the infarct patterns on diffusion-weighted imaging (DWI). Methods: From January 2006 to October 2010, we retrospectively enrolled 21 acute infarct patients with bilateral high-grade ICA stenosis. The infarct patterns were divided into territory, cortical border-zone and internal border-zone by DWI. Results: The milder ICA stenosis side had a lower risk of ischemic stroke (4 of 20). None of the 8 patients with bilateral severe ICA stenosis (70–99%) suffered ischemic stroke ipsilateral to the milder ICA stenosis side. No single infarct mechanism was prominent: 10 of 21 infarcts were cortical border-zone pattern, followed by internal border-zone (7 of 21) and territory. The difference in frequency of bilateral severe ICA stenosis between the three infarct mechanisms was not significant (p = 0.856). Conclusions: Cerebral infarcts occurred less frequently in the ipsilateral to milder ICA stenosis side, especially in bilateral severe ICA stenosis. The similar frequencies and hemodynamic status between the three infarct pattern groups indicated that both artery-to-artery emboli and being hemodynamically compromised contribute synergistically to bilateral ICA stenosis.

Innate Immune Activity in Plaque of Patients with Untreated andl-Thyroxine-Treated Subclinical Hypothyroidism

A strong association between subclinical hypothyroidism (SCH) and atherosclerotic diseases, independent of the traditional risk factors, was noted. The objective of the study was to evaluate the association between SCH and the inflammatory potential of atherosclerotic plaques as well as the role of L-T(4) replacement therapy (LTR) on regulation of plaque inflammation. EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES: We examined the differences in macrophage content, proinflammatory cytokine infiltration, and oxidative stress between asymptomatic carotid plaques of patients with and without SCH and LTR. Plaques were obtained from 23 SCH patients with LTR (treated), 34 untreated SCH patients, and 30 control patients without SCH enlisted to undergo carotid endarterectomy for extracranial high-grade (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T lymphocytes, human leukocyte antigen (HLA)-DR(+) cells, nuclear factor-κB (NF-κB), inhibitory-κBβ (IκBβ), TNF-α, nitrotyrosine, matrix metalloproteinase-9 (MMP-9), and collagen content (immunohistochemistry and ELISA). Compared with control plaques, SCH plaques had more macrophages, T lymphocytes, and HLA-DR(+) cells, TNF-α, NF-κB, markers of oxidative stress (nitrotyrosine and O(2-) production), and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBβ levels (P < 0.001). Compared with plaques from treated patients, plaques from untreated patients had more macrophages, T lymphocytes, HLA-DR(+) cells, TNF-α, NF-κB (P < 0.001), nitrotyrosine, O(2-) production, and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBβ levels (P<0.001). These data suggest a potential interplay between SCH and inflammatory activity in atherosclerotic plaque progression toward instability. Moreover, LTR might contribute to plaque stabilization by inhibiting the innate immunity-dependent plaque rupture in patients with SCH.

N-terminal pro B-type natriuretic peptide (NT pro-BNP) is a predictor of long-term survival in male patients of 75 years and older with high-grade asymptomatic internal carotid artery stenosis

Carotid endarterectomy (CEA) is commonly performed for asymptomatic high-grade internal carotid artery (ICA) stenosis to prevent stroke. However, despite advancing age of the society, for patients older than 75 years, there is no recommendation by the European guidelines for CEA, as this age group might not benefit from this intervention due to a limited life expectancy. We assessed N-terminal pro B-type natriuretic peptide (NT pro-BNP) as a predictive marker for long-term survival in this particular patient population in order to stratify patients for an improved surgical outcome. In a nonrandomized single-center clinical trial, we prospectively studied mortality rates of 205 consecutive patients (80 women, 125 men; mean age, 75 ± 10 years) with asymptomatic high-grade ICA stenosis in relation to preoperative plasma NT pro-BNP levels. We estimated cumulative survival over 5 years by Kaplan-Meier curves and established a proportional hazard-model by Cox regression. In male patients, higher levels of preoperative NT pro-BNP levels were associated with a significantly increased long-term mortality. Those 75 years or older had the same survival rate as younger patients, if NT pro-BNP levels were low, making them thus eligible for CEA. The results of our study suggest that preoperative plasma levels of NT pro-BNP are a valuable tool for the stratification of male patients. Male patients older than 75 years with low levels of NT pro-BNP should be referred for carotid revascularization, as they will most likely enjoy the benefit of surgery.

Cognitive dysfunction in patients with asymptomatic ischaemic disturbances of the cerebral circulation and carotid stenosis

BACKGROUND: Impairment of cognitive function is often present in patients with carotid artery stenosis but the details of this dysfunction have rarely been reported. Our purpose was to elucidate the cognitive dysfunction in patients with Asymptomatic Ischaemic Disturbances of the Cerebral Circulation and unilateral asymptomatic severe carotid stenosis using comprehensive neuropsychological testing, and also to identify the specific underlying clinical and neuroimaging factors. METHODS: We analyzed the results of neuropsychological testing, the clinical history, and MR findings in 10 patients with Asymptomatic Ischaemic Disturbances of the Cerebral Circulation and severe (70-99%) stenosis of the extra cranial internal carotid artery (ICA) on Doppler sonography. Cognitive functions were examined. We excluded patients with Asymptomatic Ischaemic Disturbances of the Cerebral Circulation with contra lateral ICA occlusion or severe stenosis. RESULTS: Our neuropsychological testing revealed obvious cognitive deficits in all patients with Asymptomatic Ischaemic Disturbances of the Cerebral Circulation and unilateral asymptomatic severe ICA stenosis. The mean cognitive score on the memory test was also significantly lower in patients with asymptomatic ICA stenosis and score 3 lesions on MRI than in asymptomatic patients and lesions score 1 on MRI (p<0.05). CONCLUSIONS: Cognitive deficits are common in patients with Asymptomatic Ischaemic Disturbances of the Cerebral Circulation and unilateral asymptomatic severe ICA stenosis. Our findings suggest that an additional mechanism beyond the structural lesion such as chronic hypoperfusion may affect cognitive function in patients with high-grade ICA stenosis.

High-Grade Internal Carotid Artery Stenosis and Chronic Brain Damage: A Volumetric Magnetic Resonance Imaging Study

Background: Experimental data suggest that high-grade vascular stenosis may induce chronic cerebral tissue damage. Methods: We tested this hypothesis in 97 patients with a ≧70% unilateral internal carotid artery (ICA) stenosis (mean age: 69.1 ± 10.2 years), comparing intraindividual side-to-side differences in hemispheric brain and white matter hyperintensity (WMH) volumes. Patients with a supratentorial infarct exceeding 1.5 cm in diameter were excluded. Results: Overall, the median WMH volume was greater in the hemisphere ipsilateral to the stenotic ICA (1.13 ± 2.65 vs. 0.77 ± 2.26 cm³; p = 0.005), but there were no differences in hemispheric brain volumes between the stenotic and nonstenotic sides. In the subgroup of patients with moderate and severe WMH (n = 41), the hemispheric volume ipsilateral to the stenotic ICA was significantly smaller (543.46 ± 22.17 vs. 548.66 ± 26.7 cm³; p = 0.03). Multivariate linear regression analysis revealed an independent effect of WMH grade on interhemispheric volume differences relative to the side of stenosis. Conclusions: Chronic tissue damage may occur in a subset of individuals with ≧70% ICA stenosis, globally exhibiting more extensive WMH.

Limb-Shaking Transient Ischaemic Attacks in Patients With Internal Carotid Artery Occlusion: A Case-Control Study

Conclusion: Transient ischemic attacks (TIAs) marked by limb-shaking are associated with high-grade carotid stenosis or internal carotid artery occlusion and can be recognized by short duration and precipitation by rising or exercise. They are also accompanied frequently by paresis and indicate an impaired hemodynamic state of the brain. Summary: Case-reports have described limb-shaking as an unusual clinical feature of TIAs (Klijn CJ, et al [Neurology 2000; 55: 1806-12] and Firlik AD, et al [Neurosurgery 1996;39:607-11]). The limb-shaking characterizing these TIAs consists of brief, jerky, and coarse involuntary movements involving an arm or a leg and has been associated with high-grade stenosis or occlusion of the internal carotid artery (ICA). An unanswered question is whether patients with high-grade ICA stenosis or occlusion who have limb-shaking TIAs have a worse hemodynamic flow state than patients with ICA stenosis or occlusion who do not have limb-shaking TIAs. In this study the authors sought to describe clinical characteristics of limb-shaking in patients with TIAs or moderately disabling strokes associated with occlusion of the ICA. They also sought to investigate whether the hemodynamic state of the patients with limb-shaking is worse than in patients with symptomatic ICA occlusion without limb-shaking. The authors studied 34 patients (82% men; mean age, 62 ± 7 years) who had limb-shaking associated with ICA occlusion and 68 age-matched and sex-matched controls who had hemispheric TIAs or minor disabling strokes and ICA occlusion but who did not have limb-shaking. They investigated collateral pathways using contrast angiograms and also studied carbon dioxide reactivity measured by transcranial Doppler imaging. Limb-shaking TIAs were found to last <5 minutes and were often accompanied by paresis of the involved limb. Patients with limb-shaking TIAs compared with controls more frequently had symptoms precipitated by exercise or rising (odds ratio [OR], 14.2; 95% confidence interval [CI], 4.2-47.9). Patients with limb-shaking TIAs also more frequently had recurrent ischemic deficits after ICA occlusion before inclusion in this study (OR, 8.2; 95% CI, 2.3-29.3). Patients with limb-shaking TIA's also tended to have lower carbon dioxide reactivity (mean, 5% ± 16% vs 12% ± 17%; OR. 0.97 per 1% increase; 95% CI, 0.94-1.00). Patients with limb-shaking TIAs had a greater dependence on leptomeningeal collaterals (OR, 6.8; 95% CI, 2.0-22.7). Comment: Limb shaking as a manifestation of a TIA is a relatively unknown to most vascular surgeons. Most of these patients have ICA occlusion; 10% of patients with ICA occlusion will have limb-shaking TIAs. Some of these patients, however, have high-grade ICA stenosis rather than occlusion and therefore are of interest to the peripheral vascular surgeon. It is important to note that this particular form of TIA is likely hemodynamic and not embolic. Patients with limb-shaking TIAs undergoing carotid endarterectomy therefore, perhaps, should be strongly considered for shunting during the performance of the endarterectomy when technically feasible.

Angioplasty and Stent Placement in Symptomatic Internal Carotid Occlusion

Conclusion: Carotid artery angioplasty and stenting can be successfully performed in patients with internal carotid artery pseudo-occlusion or string sign. Summary: This report focuses on carotid angioplasty and stenting in a series of patients in whom the internal carotid artery (ICA) was thought occluded by conventional ultrasound but who actually had string signs. The authors treated 16 patients. Contrast computed tomography (CT) showed a patent distal ICA in 14 of the 16 patients treated. Contrast-enhanced ultrasound imaging also showed patent distal ICAs in 13 cases. This is actually a series of very high-grade ICA stenosis and/or string signs treated with angioplasty and stenting. The authors performed the angioplasty and stent placement under cerebral protection. Duplex imaging was performed at 14 days, 3 months, and every 6 months thereafter. CT scans were obtained at 2 to 9 months, and the mean follow-up period was 9.9 months. Most patients had nonhemispheric symptoms as the indication for treatment. Patients were treated with clopidogrel and aspirin before the procedure and were maintained on clopidogrel 90 days after treatment and on aspirin indefinitely. A 6F sheath was placed in the common carotid artery and the ICA accessed with a 5F diagnostic vertebral catheter. A 0.035-inch hydrophilic guide wire was then passed into the ICA, followed by the catheter. An interceptor filter (Medtronic, Minneapolis, MN) was passed through the catheter and opened in the lumen, and then the catheter was withdrawn. Predilation was performed with a 3-mm balloon through the filter wire, and then a self-expanding stent was placed in the proximal ICA and dilated with a 5-mm balloon. If necessary, a second distal stent was placed. Stent placement was successful in 13 of 16 patients. There were no deaths, conversions, or cardiac complications. One patient had paresis in the upper limb with recovery in 3 months. At follow-up, all 13 patients remained with patent arterial lumens and were symptom free. After 2 to 9 months, so-called string signs had calibers close or equal to those of normal arteries. Comment: The title of this article is misleading. Although conventional duplex ultrasound imaging showed the patients had occluded ICAs, all in fact had patent distal ICAs either by contrast-enhanced ultrasound or contrast CT scanning. The authors of the article, the Journal of Vascular and Interventional Radiology reviewers, and the editors should be ashamed for permitting such a misleading title. What the authors have shown us is that in their institution, conventional duplex ultrasound imaging is likely below standard in distinguishing high-grade carotid stenosis from occlusion. They have shown us that CT angiography and contrast-enhanced ultrasound imaging can detect carotid string signs, something we already knew. They have also shown us that if you can get a wire across a high-grade stenosis, then you can perform angioplasty and stenting, again something we already knew. They have demonstrated that such procedures can be performed, but whether they should be performed is an entirely different question.