Extracranial Carotid Plaque Calcification and Cerebrovascular Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less clear. As a result, we performed a systematic review and meta-analysis to evaluate the association between extracranial carotid artery plaque calcification burden and ipsilateral cerebrovascular ischemic events. METHODS: A comprehensive literature search was performed in the following databases: Ovid MEDLINE(R) 1946 to July 6, 2022; OVID Embase 1974 to July 6, 2022; and The Cochrane Library (Wiley). We performed meta-analyses including studies in which investigators performed a computed tomography assessment of calcification volume, percentage, or other total calcium burden summarizable in a single continuous imaging biomarker and determined the association of these features with the occurrence of ipsilateral stroke or transient ischemic attack. RESULTS: Our overall meta-analysis consisted of 2239 carotid arteries and 9 studies. The presence of calcification in carotid arteries ipsilateral to ischemic stroke or in stroke patients compared with asymptomatic patients did not demonstrate a significant association with ischemic cerebrovascular events (relative risk of 0.75 [95% CI, 0.44-1.28]; P=0.29). When restricted to studies of significant carotid artery stenosis (>50%), the presence of calcification was associated with a reduced risk of ischemic stroke (relative risk of 0.56 [95% CI, 0.38-0.85]; P=0.006). When the analysis was limited to studies of patients with mainly nonstenotic plaques, there was an increased relative risk of ipsilateral ischemic stroke of 1.72 ([95% CI, 1.01-2.91]; P=0.04). Subgroup meta-analyses of total calcium burden and morphological features of calcium showed wide variability in their strength of association with ischemic stroke and demonstrated significant heterogeneity. CONCLUSIONS: The presence of calcification in carotid plaque confers a reduced association with ipsilateral ischemic events, although these results seem to be limited among carotid arteries with higher degrees of stenosis. Adoption of carotid calcification measures in clinical decision-making will require additional studies providing more reproducible and standardized methods of calcium characterization and testing these imaging strategies in prospective studies.

Association between high-risk extracranial carotid plaque and covert brain infarctions and cerebral microbleeds.

PURPOSE: Covert brain infarctions (CBIs) and cerebral microbleeds (CMBs) represent subclinical sequelae of ischemic and hemorrhagic cerebral small vessel disease, respectively. In addition to thromboembolic stroke, carotid atherosclerosis has been associated with downstream vascular brain injury, including inflammation and small vessel disease. The specific plaque features responsible for this are unknown. We aimed to determine the association of specific vulnerable carotid plaque features to CBIs and CMBs to better understand the relation of large and small vessel disease in a single-center retrospective observational study. METHODS: Intraplaque hemorrhage (IPH) and plaque ulceration were recorded on carotid MRA and total, cortical, and lacunar CBIs and CMBs were recorded on brain MR in 349 patients (698 carotid arteries). Multivariable Poisson regression was performed to relate plaque features to CBIs and CMBs. Within-subject analysis in those with unilateral IPH and ulceration was performed with Poisson regression. RESULTS: Both IPH and plaque ulceration were associated with total CBI (prevalence ratios (PR) 3.33, 95% CI: 2.16-5.15 and 1.91, 95% CI: 1.21-3.00, respectively), after adjusting for stenosis, demographic, and vascular risk factors. In subjects with unilateral IPH, PR was 2.83, 95% CI: 1.76-4.55, for CBI in the ipsilateral hemisphere after adjusting for stenosis. Among those with unilateral ulceration, PR was 1.82, 95% CI: 1.18-2.81, for total CBI ipsilateral to ulceration after adjusting for stenosis. No statistically significant association was seen with CMBs. CONCLUSION: Both IPH and plaque ulceration are associated with total, cortical, and lacunar type CBIs but not CMBs suggesting that advanced atherosclerosis contributes predominantly to ischemic markers of subclinical vascular injury.

Association between Extracranial Carotid Artery Plaque and Cognitive Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or carotid stenosis; however, there is evidence that carotid plaque may contribute to dementia, perhaps via microembolic phenomena. OBJECTIVES: We sought to evaluate the role of carotid plaque in contributing to cognitive impairment by performing a systematic review and meta-analysis to summarize the association between extracranial carotid plaque and cognitive dysfunction and dementia. METHODS: We performed a comprehensive literature search evaluating the association of extracranial carotid plaque with cognition. We included studies measuring carotid plaque on ultrasound, computed tomography, or MR and also evaluated cognition through neuropsychological testing. Meta-analyses with assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. RESULTS: After screening 1,674 studies, we included 40 for systematic review and 16 and 7 studies for two meta-analyses with a total of 19,029 and 27,325 patients, respectively. We found a positive relationship between the presence of extracranial carotid plaque and cognitive dysfunction with a pooled random-effects odds ratio (OR) of 1.83 (95% CI, 1.50, 2.24) and a pooled random-effects hazard ratio (HR) of 1.47 (95% CI, 1.15, 1.89), respectively. A sensitivity analysis of only longitudinal studies found a persistent positive association. Measures of heterogeneity showed moderate heterogeneity in each meta-analysis, respectively (I-squared statistic = 57% and 70%). CONCLUSION: The presence of extracranial carotid plaque is significantly associated with cognitive dysfunction and dementia in both cross-sectional and longitudinal analyses. After further confirmation, our results support carotid plaque being a potentially modifiable risk factor in the development of dementia.

Optimal Management of Asymptomatic Carotid Stenosis in 2021: The Jury is Still Out. An International, Multispecialty, Expert Review and Position Statement.

OBJECTIVES: The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement is to reconcile the conflicting views on the topic. MATERIALS AND METHODS: A literature review was performed with a focus on data from recent studies. RESULTS: Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients < 75 years and microembolic signals on transcranial Doppler. There is growing evidence that 80-99% ACS indicate a higher stroke risk than 50-79% stenoses. CONCLUSIONS: Although aggressive risk factor control and BMT should be implemented in all ACS patients, several high-risk features that may increase the risk of a future cerebrovascular event are now documented. Consequently, some guidelines recommend a prophylactic carotid intervention in high-risk patients to prevent future cerebrovascular events. Until the results of the much-anticipated randomized controlled trials emerge, the jury is still out regarding the optimal management of ACS patients.

Differentiation of symptomatic and asymptomatic carotid intraplaque hemorrhage using 3D high-resolution diffusion-weighted stack of stars imaging.

Ischemic events related to carotid disease are far more strongly associated with plaque instability than stenosis. 3D high-resolution diffusion-weighted (DW) imaging can provide quantitative diffusion measurements on carotid atherosclerosis and may improve detection of vulnerable intraplaque hemorrhage (IPH). The 3D DW-stack of stars (SOS) sequence was implemented with 3D SOS acquisition combined with DW preparation. After simulation of signals created from 3D DW-SOS, phantom studies were performed. Three healthy subjects and 20 patients with carotid disease were recruited. Apparent diffusion coefficient (ADC) values were statistically analyzed on three subgroups by using a two-group comparison Wilcoxon-Mann-Whitney U test with p values less than 0.05: symptomatic versus asymptomatic; IPH-positive versus IPH-negative; and IPH-positive symptomatic versus asymptomatic plaques to determine the relationship with plaque vulnerability. ADC values calculated by 3D DW-SOS provided values similar to those calculated from other techniques. Mean ADC of symptomatic plaque was significantly lower than asymptomatic plaque (0.68 ± 0.18 vs. 0.98 ± 0.16 x 10-3  mm2 /s, p < 0.001). ADC was also significantly lower in IPH-positive versus IPH-negative plaque (0.68 ± 0.13 vs. 1.04 ± 0.11 x 10-3  mm2 /s, p < 0.001). Additionally, ADC was significantly lower in symptomatic versus asymptomatic IPH-positive plaque (0.57 ± 0.09 vs. 0.75 ± 0.11 x 10-3  mm2 /s, p < 0.001). Our results provide strong evidence that ADC measurements from 3D DW-SOS correlate with the symptomatic status of extracranial internal carotid artery plaque. Further, ADC improved discrimination of symptomatic plaque in IPH. These data suggest that diffusion characteristics may improve detection of destabilized plaque leading to elevated stroke risk.

Carotid artery plaque characteristics: current reporting practices on CT angiography.

PURPOSE: Extracranial ICA imaging has largely focused on the degree of luminal stenosis, but recent advances suggest specific plaque features are crucial in stroke risk assessment. We evaluated the current state of reporting carotid plaque features on neck CTAs at an academic institution. METHODS: In this retrospective observational study, we included neck CTAs performed on patients over age 50 with any reported carotid plaque. We evaluated reports for mention of the following: degree of luminal stenosis, soft plaque, calcified plaque, plaque thickness, quantification of soft and calcified plaque, plaque ulceration, and increased risk associated with specific features. We used Fisher's exact test to compare how often each feature was mentioned. RESULTS: We included a total of 651 reports from unique patients (mean age, 68.1 ± 13.3 years). A total of 639 reports (98.1%) explicitly mentioned degree of stenosis per NASCET criteria. Specific plaque features were less frequently characterized: soft plaque in 116 (17.8%); calcified plaque in 166 (25.5%); quantification of the amount of soft plaque and calcified plaque in 24 (3.7%) and 16 (2.5%) reports, respectively; plaque thickness in 12 (1.8%); plaque ulceration in 476 (73.1%); and increased risk associated with plaque in 2 (0.3%). Degree of stenosis was statistically more likely to be mentioned than any other plaque feature (p < 0.001). CONCLUSION: Currently, nearly all reports mention the degree of luminal stenosis on neck CTAs while a significant minority mention specific plaque features. Despite mounting evidence of the importance of carotid plaque features in stroke risk assessment, radiology reports do not routinely report these findings.

Reclassification of Ischemic Stroke Etiological Subtypes on the Basis of High-Risk Nonstenosing Carotid Plaque.

Background and Purpose- Carotid artery plaque with <50% luminal stenosis may be an underappreciated stroke mechanism. We assessed how many stroke causes might be reclassified after accounting for nonstenosing plaques with high-risk features. Methods- We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results- Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2-6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4-3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1-2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4-3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7-3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions- High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

Carotid Plaque Positron Emission Tomography Imaging and Cerebral Ischemic Disease.

Background and Purpose- The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18F-fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18F-FDG or 18F-NaF uptake and recent or future cerebral ischemic events. Methods- A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen's d metric. Results- After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18F-FDG uptake than asymptomatic arteries (Cohen's d =0.492; CI=0.130-0.855; P=0.008) as well as significant heterogeneity (Cochran's Q =31.5; P=0.0005; I2=68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions- Recent ipsilateral cerebral ischemia may be associated with increased carotid 18F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18F-FDG or 18F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.

Angiographic Blush after Mechanical Thrombectomy is Associated with Hemorrhagic Transformation of Ischemic Stroke.

BACKGROUND AND PURPOSE: Risk factors for hemorrhagic transformation of ischemic stroke after mechanical thrombectomy (MT) are not well established. We conducted a study to determine if prominent angiographic cerebral vascularity following recanalization with thrombectomy (angiographic blush) is associated with hemorrhagic transformation. METHODS: Using the Cornell AcutE Stroke Academic Registry, we identified stroke patients who had thrombectomy and achieved recanalization of anterior circulation large-vessel occlusion between 2012 and 2015. The exposure variable was presence of angiographic blush after recanalization, defined as capillary blush with or without early venous drainage. The primary outcome was volume of hemorrhagic transformation on brain imaging after thrombectomy, as determined by semiautomated volumetric analysis on computed tomography or magnetic resonance imaging among those adjudicated to have hemorrhagic conversion by neuroradiology investigators blinded to angiography results. Using a doubly robust estimator with propensity scores and outcome regression adjusting for demographics and known risk factors for hemorrhagic transformation, we evaluated whether angiographic blush after recanalization is associated with an increased volume of hemorrhagic transformation. RESULTS: Among 48 eligible patients, 31 (64.6%) had angiographic blush and 26 (54.2%) had radiographic hemorrhagic transformation (mean volume, 7.6 ml). Patients with angiographic blush averaged lower thrombolysis in cerebral infarction scores and more often received intravenous thrombolysis. In adjusted analysis, angiographic blush was associated with an increased volume of hemorrhagic transformation: mean volume, 10.3ml (95% CI, 3.7-16.9 ml) with blush versus 1.8ml (95% Confidence Interval (CII = Confidence Interval), 0.1-3.4 ml) without (P = .01). CONCLUSIONS: Presence of angiographic blush after MT was independently associated with the volume of hemorrhagic transformation.

Magnetic resonance spectroscopy abnormalities in traumatic brain injury: A meta-analysis.

BACKGROUND AND PURPOSE: Despite traumatic brain injury (TBI) being common, evaluation with imaging remains challenging. Magnetic resonance spectroscopy (MRS) shows promise in detecting changes of brain metabolite concentrations following TBI; however, currently there are only small studies available without conclusive evidence of the technique's efficacy. The purpose of this systematic review and meta-analysis was to evaluate the association between TBI and MRS metabolite changes. MATERIALS & METHODS: A comprehensive literature search was performed looking for studies reporting brain metabolite concentrations in both TBI and control subjects. Included studies reported values for both adult TBI and control subjects. Cumulative and subgroup meta-analyses were performed using a random effects model. RESULTS: The literature search returned an initial 898 manuscripts, of which 36 (which included 748 unique subjects) met study criteria. Cumulatively, NAA/Cr ratios in TBI patients showed a significant decrease as compared to controls (standardized mean deviation [SMD]=-0.88, P<0.0001). When broken into subgroups by severity, the severe and mixed TBI subgroups showed decreases, but the mild TBI (mTBI) subgroup did not. When stratified by time, a significant decrease was seen in the subacute and chronic phases but not the acute phase. Cumulative post-TBI Cho/Cr levels were increased compared to controls (SMD=0.69, P=0.0002). Significant changes were seen in all subgroups except the mild and mixed mTBI subgroups and the acute phase subgroup. CONCLUSION: Current evidence shows that MRS is able to detect changes to metabolites following TBI, but not in patients with mTBI or in the acute stage.

Neutrophil-Lymphocyte Ratio and Perihematomal Edema Growth in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Although preclinical studies have shown inflammation to mediate perihematomal edema (PHE) after intracerebral hemorrhage, clinical data are lacking. Leukocyte count, often used to gauge serum inflammation, has been correlated with poor outcome but its relationship with PHE remains unknown. Our aim was to test the hypothesis that leukocyte count is associated with PHE growth. METHODS: We included patients with intracerebral hemorrhage admitted to a tertiary-care stroke center between 2011 and 2015. The primary outcome was absolute PHE growth during 24 hours, calculated using semiautomated planimetry. Linear regression models were constructed to study the relationship between absolute and differential leukocyte counts (monocyte count and neutrophil-lymphocyte ratio) and 24-hour PHE growth. RESULTS: A total of 153 patients were included. Median hematoma and PHE volumes at baseline were 14.4 (interquartile range, 6.3-36.3) and 14.0 (interquartile range, 5.9-27.8), respectively. In linear regression analysis adjusted for demographics and intracerebral hemorrhage characteristics, absolute leukocyte count was not associated with PHE growth (ß, 0.07; standard error, 0.15; P=0.09). In secondary analyses, neutrophil-lymphocyte ratio was correlated with PHE growth (ß, 0.22; standard error, 0.08; P=0.005). CONCLUSIONS: Higher neutrophil-lymphocyte ratio is independently associated with PHE growth. This suggests that PHE growth can be predicted using differential leukocyte counts on admission.

The Association between Carotid Artery Atherosclerosis and Silent Brain Infarction: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid atherosclerosis is responsible for ~20% of ischemic strokes, but it is unclear whether carotid disease is associated with the presence of downstream silent brain infarction (SBI). We performed a systematic review and meta-analysis to study the relationship between SBI and 2 separate manifestations of carotid atherosclerosis, carotid intima-media thickening (IMT) and luminal stenosis. METHODS: Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database were searched with an additional search of references and citing articles of target studies. Articles were included if they reported an association between carotid IMT or stenosis and magnetic resonance imaging-defined SBI, excluding SBIs found after carotid intervention. RESULTS: We pooled 7 studies of carotid IMT reporting on 1469 subjects with SBI and 5102 subjects without SBI. Subjects with SBI had a larger mean IMT than subjects without SBI (pooled standardized mean difference, .37; 95% confidence interval [CI], .23-.51; P < .0001). We pooled 11 studies of carotid stenosis reporting on 12,347 subjects (2110 subjects with carotid stenosis and 10,237 subjects without carotid stenosis). We found a higher prevalence of SBI among subjects with carotid stenosis (30.4% versus 17.4%). Our pooled random-effects analysis showed a significant positive relationship between carotid stenosis and SBI (odds ratio, 2.78; 95% CI, 2.19-3.52; P < .0001). CONCLUSIONS: Two forms of atherosclerotic disease, carotid IMT and stenosis, are both significantly associated with SBI. This review highlights a lack of consistent definitions for carotid disease measures and little evidence evaluating SBI prevalence downstream from carotid stenosis.

Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis.

OBJECTIVE: Because some cryptogenic strokes may result from large-artery atherosclerosis that goes unrecognized as it causes <50% luminal stenosis, we compared the prevalence of nonstenosing intracranial atherosclerotic plaques ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using imaging biomarkers of calcium burden. METHODS: In a prospective stroke registry, we identified patients with cerebral infarction limited to the territory of one internal carotid artery (ICA). We included patients with stroke of undetermined etiology and, as controls, patients with cardioembolic stroke. We used noncontrast computed tomography to measure calcification in both intracranial ICAs, including qualitative calcium scoring and quantitative scoring utilizing the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed-rank sum test for nonparametric paired data was used to compare the calcium burden in the ICA upstream of the infarction versus the ICA on the unaffected side. RESULTS: We obtained 440 calcium measures from 110 ICAs in 55 patients. Among 34 patients with stroke of undetermined etiology, we found greater calcium in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale score, 6.7 ± 4.6) compared with the contralateral side (5.4 ± 4.1) (P = .005). Among 21 patients with cardioembolic stroke, we found no difference in calcium burden ipsilateral to the infarction (6.7 ± 5.9) versus the contralateral side (7.3 ± 6.3) (P = .13). The results were similar using quantitative calcium measurements, including the AJ calcium scores. CONCLUSION: In patients with strokes of undetermined etiology, the burden of calcified intracranial large-artery plaque was associated with downstream cerebral infarction.

Silent Brain Infarction in Patients With Asymptomatic Carotid Artery Atherosclerotic Disease.

BACKGROUND AND PURPOSE: The relationship between carotid atherosclerosis and ipsilateral silent brain infarction (SBI) is unclear. We tested the hypothesis that extracranial internal carotid artery (ICA) stenosis is associated with a greater prevalence of SBI in the cerebral hemisphere ipsilateral to ICA disease compared with the unaffected, contralateral side. METHODS: We identified patients with unilateral extracranial ICA stenosis ≥50% on angiography by standard imaging criteria. We included patients with recent brain magnetic resonance imaging who had no previous history of stroke or transient ischemic attack. Blinded readers ascertained the presence of anterior circulation SBIs. SBI was defined as either a cavitary lacunar infarction in the white or deep gray matter or cortical infarction defined by T2 hyperintense signal in cortical gray matter. The Wilcoxon signed-rank test was used to compare SBI in the cerebral hemispheres and Cohen κ to assess inter-rater reliability of SBI evaluation. RESULTS: Among 104 patients, we found a higher prevalence of SBIs ipsilateral to ICA disease (33%) compared with the contralateral side (20.8%; P=0.0067). There was no significant difference in the prevalence of lacunar SBIs (including both white and deep gray matter) between hemispheres (P=0.109), but there was a significantly higher prevalence of cortical SBIs occurring downstream from ICA disease (P=0.0045). High inter-rater reliability was observed (κ=0.818). CONCLUSIONS: Patients with asymptomatic ICA disease demonstrate a higher prevalence of SBI downstream from their ICA atherosclerotic disease compared with the contralateral side but only of the cortical and not lacunar SBI subtype.

Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Ultrasonographic plaque echolucency has been studied as a stroke risk marker in carotid atherosclerotic disease. We performed a systematic review and meta-analysis to summarize the association between ultrasound-determined carotid plaque echolucency and future ipsilateral stroke risk. METHODS: We searched the medical literature for studies evaluating the association between carotid plaque echolucency and future stroke in asymptomatic patients. We included prospective observational studies with stroke outcome ascertainment after baseline carotid plaque echolucency assessment. We performed a meta-analysis and assessed study heterogeneity and publication bias. We also performed subgroup analyses limited to patients with stenosis ≥50%, studies in which plaque echolucency was determined via subjective visual interpretation, studies with a relatively lower risk of bias, and studies published after the year 2000. RESULTS: We analyzed data from 7 studies on 7557 subjects with a mean follow-up of 37.2 months. We found a significant positive relationship between predominantly echolucent (compared with predominantly echogenic) plaques and the risk of future ipsilateral stroke across all stenosis severities (0% to 99%; relative risk, 2.31; 95% confidence interval, 1.58-3.39; P<0.001) and in subjects with ≥50% stenosis (relative risk, 2.61; 95% confidence interval, 1.47-4.63; P=0.001). A statistically significant increased relative risk for future stroke was preserved in all additional subgroup analyses. No statistically significant heterogeneity or publication bias was present in any of the meta-analyses. CONCLUSIONS: The presence of ultrasound-determined carotid plaque echolucency provides predictive information in asymptomatic carotid artery stenosis beyond luminal stenosis. However, the magnitude of the increased risk is not sufficient on its own to iden tify patients likely to benefit from surgical revascularization.

Detection of Symptomatic Carotid Plaque Using Source Data from MR and CT Angiography: A Correlative Study.

BACKGROUND: Carotid plaque MRI has been a useful method to characterize vulnerable atherosclerotic plaque elements. Recent investigations have suggested that source images from CT angiography (CTA) and MR angiography (MRA) can identify the simple high-risk features of symptom-producing carotid artery plaque. We studied the correlation and relative diagnostic accuracies of CTA and MRA source images in detecting symptomatic carotid artery plaque. METHODS: Subjects were eligible if they had carotid stenosis between 50 and 99% and had MRA and CTA exams performed within 10 days of one another. We measured the soft (non-calcified) plaque and hard (calcified) plaque thickness on CTA axial source images and intraplaque high-intensity signal (IHIS) on 3D-time-of-flight MRA source images in subjects. We assessed whether a correlation existed between increasing CTA soft plaque thicknesses and the presence of MRA IHIS using the Student's t-test. We calculated the differences in sensitivity and specificity measures of CTA and MRA source-imaging data with the occurrence of recent ipsilateral stroke or transient ischemic attack (TIA) as the reference standard. We also performed logistic regression analyses to evaluate the predictive strength of plaque showing both IHIS and increased CTA soft plaque thickness in predicting symptomatic disease status. RESULTS: Of 1994 screened patients, 48 arteries met the final inclusion criteria with MRA and CTA performed within 10 days of one another. The mean and median time between CTA and MRA exams were 2.0 days and 1 day, respectively. A total of 34 of 48 stenotic vessels (70.8%) were responsible for giving rise to ipsilateral stroke or TIA. CTA mean soft plaque thickness was significantly greater (4.47 vs. 2.30 mm, p < 0.0001) in patients with MRA-defined IHIS, while CTA hard plaque thickness was significantly greater (2.09 vs. 1.16 mm, p = 0.0134) in patients without MRA evidence of IHIS. CTA soft plaque thickness measurements were more sensitive than MRA IHIS (91.2 vs. 67.6%, p = 0.011) in detecting symptomatic plaque, while differences in specificity were not significantly different (p = 0.1573). In the subset of patients with both IHIS on MRA and plaque thickness >2.4 mm on CTA, the odds ratio of detecting symptomatic plaque, corrected for stenosis severity, was 45.3 (p < 0.0005). CONCLUSIONS: Unprocessed source images from CTA and MRA, which are routinely evaluated for clinical studies demonstrate the highly correlated presence of IHIS and increasing soft plaque thickness. In particular, plaque that shows high-risk features on both MRA and CTA are very strongly associated with symptom-producing carotid plaque. With further validation, such techniques are promising practical methods of extracting risk information from routine neck angiographic imaging.

Evaluation of computed tomography angiography plaque thickness measurements in high-grade carotid artery stenosis.

BACKGROUND AND PURPOSE: Increasing evidence suggests that carotid artery imaging can identify vulnerable plaque elements that increase stroke risk. We correlated recently proposed markers, soft and hard plaque thickness measurements on axial computed tomography angiography source images, with symptomatic disease status (ipsilateral stroke or transient ischemic attack) in high-grade carotid disease. METHODS: Soft plaque and hard plaque thickness were measured with a recently validated technique using computed tomography angiography source images in subjects with ≥70% extracranial carotid artery stenosis. Logistic regression analyses were used to assess the strength of association between soft and hard plaque thickness measurements and previous stroke or transient ischemic attack. Receiver operating characteristic analysis was also performed. RESULTS: Compared with asymptomatic subjects, those with symptomatic carotid disease had significantly larger soft plaque and total plaque thickness measurements and smaller hard plaque thickness measurements. Each 1-mm increase in soft plaque resulted in a 2.7 times greater odds of previous stroke or transient ischemic attack. Soft plaque thickness measurements provided excellent discrimination between symptomatic and asymptomatic disease, with receiver operating characteristic analysis showing an area under the curve of 0.90. A cutoff of 3.5-mm maximum soft plaque thickness provided a sensitivity of 81%, specificity of 83%, positive predictive value of 85%, and a negative predictive value of 78%. CONCLUSIONS: Increasing maximum soft plaque thickness measurements are strongly associated with symptomatic disease status in carotid artery stenosis. Prospective validation of these results may translate into a widely accessible stroke risk stratification tool in high-grade carotid artery atherosclerotic disease.

Management Patterns and Outcomes After Traumatic Brain Injury With Associated Blunt Cerebrovascular Injury.

BACKGROUND AND OBJECTIVES: Although blunt cerebrovascular injuries (BCVIs) are relatively common in patients with traumatic brain injuries (TBIs), uncertainty remains regarding optimal management strategies to prevent neurological complications, morbidity, and mortality. Our objectives were to characterize common care patterns; assess the prevalence of adverse outcomes, including stroke, functional deficits, and death, by BCVI grade; and evaluate therapeutic approaches to treatment in patients with BCVI and TBI. METHODS: Patients with TBI and BCVI treated at our Level I trauma center from January 2016 to December 2020 were identified. Presenting characteristics, treatment, and outcomes were captured for univariate and multivariate analyses. RESULTS: Of 323 patients with BCVI, 145 had Biffl grade I, 91 had grade II, 49 had grade III, and 38 had grade IV injuries. Lower-grade BCVIs were more frequently managed with low-dose (81 mg) aspirin ( P < .01), although all grades were predominantly treated with high-dose (150-600 mg) aspirin ( P = .10). Patients with low-grade BCVIs had significantly fewer complications ( P < .01) and strokes ( P < .01). Most strokes occurred in the acute time frame (<24 hours), including 10/11 (90.9%) grade IV-related strokes. Higher BCVI grade portended elevated risk of stroke (grade II odds ratio [OR] 5.3, grade III OR 12.2, and grade IV OR 19.6 compared with grade I; all P < .05). The use of low- or high-dose aspirin was protective against mortality (both OR 0.1, P < .05). CONCLUSION: In patients with TBI, BCVIs impart greater risk for stroke and other associated morbidities as their severity increases. It may prove difficult to mitigate high-grade BCVI-related stroke, considering most events occur in the acute window. The paucity of late time frame strokes suggest that current management strategies do help mitigate risks.

Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with subsequent ischemic events. METHODS: We performed a comprehensive literature search evaluating the association of carotid plaque composition on MRI with ischemic outcomes. We included cohort studies examining intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap with mean follow-up of ≥1 month and an outcome measure of ipsilateral stroke or transient ischemic attack. A meta-analysis using a random-effects model with assessment of study heterogeneity and publication bias was performed. RESULTS: Of the 3436 articles screened, 9 studies with a total of 779 subjects met eligibility for systematic review. The hazard ratios for intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap as predictors of subsequent stroke/transient ischemic attack were 4.59 (95% confidence interval, 2.91-7.24), 3.00 (95% confidence interval, 1.51-5.95), and 5.93 (95% confidence interval, 2.65-13.20), respectively. No statistically significant heterogeneity or publication bias was present in the 3 main meta-analyses performed. CONCLUSIONS: The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque is associated with increased risk of future stroke or transient ischemic attack in patients with carotid atherosclerotic disease. Dedicated MRI of plaque composition offers stroke risk information beyond measurement of luminal stenosis in carotid atherosclerotic disease.

Association Between Spotty Calcification in Nonstenosing Extracranial Carotid Artery Plaque and Ipsilateral Ischemic Stroke.

Background Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with <50% luminal stenosis of the extracranial carotid arteries. Methods and Results We used data from the CAESAR (Cornell Acute Stroke Academic Registry), a prospective registry of all patients with acute ischemic stroke admitted to our institution. We included patients who met criteria for cryptogenic stroke and underwent computed tomography angiography and brain magnetic resonance imaging. Patients with extracranial carotid artery stenosis ≥50% and patients with posterior or bilateral anterior circulation infarcts were excluded. We examined the carotid bifurcations for spotty calcifications, defined as ≥1 contiguous regions of luminal calcification ≤3 mm along the long axis of the vessel. We also measured low-density plaque and maximum plaque thickness. The eligible cohort consisted of 117 patients with a mean age of 66.7±1.65 years with a median National Institute of Health Stroke Scale stroke at the time of arrival of 6 (range, 3-13). The number of spotty calcifications present within a low-density plaque was significantly associated with ipsilateral infarction (0.3±0.8 versus 0.1±0.4, P=0.02). Maximum plaque thickness was also significantly associated with ipsilateral infarction (1.4 mm ±1.5 versus 1.0 mm ±1.1, P=0.004). Conclusions Spotty calcifications associated with low-density plaque and maximum plaque thickness were associated with ipsilateral ischemic stroke in patients with nonstenotic carotid atherosclerosis, suggesting a role as imaging markers of high-risk plaque.