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.

Extracranial carotid artery atherosclerotic plaque and APOE polymorphisms: a systematic review and meta-analysis.

Introduction: Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque. Methods: A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an 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 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between ε4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; p = .003]. Additionally, there was a significant association between patients possessing at least one ε4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; p = .03). Lastly, there was no association between ε4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; p = .30). Conclusion: APOE ε4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.

Report from the society of magnetic resonance angiography: clinical applications of 7T neurovascular MR in the assessment of intracranial vascular disease.

In recent years, ultra-high-field magnetic resonance imaging (MRI) applications have been rapidly increasing in both clinical research and practice. Indeed, 7-Tesla (7T) MRI allows improved depiction of smaller structures with high signal-to-noise ratio, and, therefore, may improve lesion visualization, diagnostic capabilities, and thus potentially affect treatment decision-making. Incremental evidence emerging from research over the past two decades has provided a promising prospect of 7T magnetic resonance angiography (MRA) in the evaluation of intracranial vasculature. The ultra-high resolution and excellent image quality of 7T MRA allow us to explore detailed morphological and hemodynamic information, detect subtle pathological changes in early stages, and provide new insights allowing for deeper understanding of pathological mechanisms of various cerebrovascular diseases. However, along with the benefits of ultra-high field strength, some challenges and concerns exist. Despite these, ongoing technical developments and clinical oriented research will facilitate the widespread clinical application of 7T MRA in the near future. In this review article, we summarize technical aspects, clinical applications, and recent advances of 7T MRA in the evaluation of intracranial vascular disease. The aim of this review is to provide a clinical perspective for the potential application of 7T MRA for the assessment of intracranial vascular disease, and to explore possible future research directions implementing this technique.

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 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.

CGRP, Migraine, and Brain MRI in CADASIL: A Pilot Study.

BACKGROUND: Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic implications. The aims of this study were to identify whether MRD or interictal serum CGRP levels impacted neuroimaging findings for those with CADASIL. MATERIALS AND METHODS: A cross-sectional analysis was performed. The primary outcomes were neuroimaging differences associated with MRD among those with migraine or interictal serum CGRP levels of those with and without migraine. MRD was defined by 2 migraine disability scales (Migraine Disability Assessment, Headache Impact Test-6). Retrospective brain magnetic resonance imaging was reviewed (average 1.7 ± 2.0 y before enrollment). Rank-sum and χ 2 tests were used. RESULTS: Those with migraine (n=25, vs. n=14 without) were younger [median 49 (25 to 82) y vs. 60 (31 to 82) y, P <0.007], had fewer cerebral microbleeds (0 to 31 vs. 0 to 50, P =0.02) and less frequently had anterior temporal lobe T2 hyperintensities [68% (17/25) vs 100% (14/14), P =0.02]. MRD scale outcomes had no significant radiographic associations. Interictal serum CGRP did not differ (migraine: n=18, 27.0±9.6 pg/mL vs. no migraine: n=10, 26.8±15.7 pg/mL, P =0.965). CONCLUSIONS: Migraine may forestall microangiopathy in CADASIL, though possibly independent of severity as measured by MRD. Interictal serum CGRP did not differ in our cohort suggesting CGRP may not be vital to migraine pathophysiology in CADASIL. Larger studies are needed to account for age differences.

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.

Calcifying Pseudoneoplasm of the Neuraxis Presenting with Vasogenic Edema and a Perilesional Cyst.

Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are uncommon benign lesions that are rarely diagnosed radiographically. We report an unusual case of a left middle cerebellar peduncle CAPNON with vasogenic edema and a perilesional cyst. The patient was a 36-year-old woman with a 20-year history of left-sided hearing loss that had recently progressed. Computed tomography and magnetic resonance imaging showed a heterogenous calcified lesion with vasogenic edema and a perilesional cyst in the left middle cerebellar peduncle. Although it is a rare radiographic feature of CAPNON, vasogenic edema should be included as a possible feature of this uncommon tumefactive lesion.

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.

The role of cross-sectional imaging of the extracranial and intracranial vasculature in embolic stroke of undetermined source.

Despite an extensive workup, nearly one third of ischemic strokes are defined as Embolic Stroke of Undetermined Source (ESUS), indicating that no clear etiologic cause has been identified. Since large vessel atherosclerotic disease is a major cause of ischemic stroke, we focus on imaging of large vessel atherosclerosis to identify further sources of potential emboli which may be contributing to ESUS. For a stroke to be considered ESUS, both the extracranial and intracranial vessels must have <50% stenosis. Given the recent paradigm shift in our understanding of the role of plaque vulnerability in ischemic stroke risk, we evaluate the role of imaging specific high-risk extracranial plaque features in non-stenosing plaque and their potential contributions to ESUS. Further, intracranial vessel-wall MR is another potential tool to identify non-stenosing atherosclerotic plaques which may also contribute to ESUS. In this review, we discuss the role of cross-sectional imaging of the extracranial and intracranial arteries and how imaging may potentially uncover high risk plaque features which may be contributing to ischemic strokes.

Association of Carotid Intima Media Thickening with Future Brain Region Specific Amyloid-ß Burden.

BACKGROUND: Carotid atherosclerosis is associated with cognitive impairment and dementia, though there is limited evidence of a direct link between carotid disease and amyloid-ß (Aß) burden. OBJECTIVE: We studied the association of baseline and progressive carotid intima media thickness (CIMT) with Aß on 11C-Pittsburgh Compound B (PiB) to determine if those with carotid atherosclerosis would have higher Aß burden. METHODS: We studied 47 participants from the Framingham Offspring cohort with carotid ultrasounds measuring CIMT at their 6th clinic examination (aged 49.5±5.7 years) and an average of 9.6 years later, and PiB imaging measuring Aß on average 22.1 years post baseline. We used multivariate linear regression analyses to relate baseline, follow-up, mean, and progression of internal carotid artery (ICA) and common carotid artery (CCA) CIMT to Aß in brain regions associated with Alzheimer's disease (AD) and related dementias (ADRD), adjusting for age, sex, and other vascular risk factors. RESULTS: Participants with higher mean ICA IMT had more Aß in the precuneus (beta±standard error [ß±SE]: 0.466±0.171 mm, p = 0.01) and the frontal, lateral, and retrosplenial regions (ß±SE: 0.392±0.164 mm, p = 0.022) after adjusting for age, sex, vascular risk factors, and medication use. We did not find an association between any CCA IMT measures and Aß or progression of ICA or CCA IMT and Aß. CONCLUSION: Carotid atherosclerosis, as measured by ICA IMT, is associated with increased Aß burden later in life. These findings support a link between vascular disease and AD/ADRD pathophysiology.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Carotid Artery Stiffness: Imaging Techniques and Impact on Cerebrovascular Disease.

Arterial stiffness is an important measure of vascular aging and atherosclerosis. Though it is measured in many well-known epidemiologic cohort studies, arterial stiffness is often overlooked in routine clinical practice for a number of reasons including difficulties in measurement, variations in definition, and uncertainties surrounding treatment. Central arterial stiffness, a surrogate for aortic stiffness, is the most commonly measured marker of arterial stiffness. In addition to central stiffness, there are also a number of ultrasound based techniques to measure local vascular stiffness, including carotid stiffness. There is evidence that both local carotid stiffness and central arterial stiffness measures are associated with multiple cerebrovascular processes, including stroke and cognitive dysfunction. Mechanistic explanations supporting this association include increased flow load experienced by the cerebral microvasculature leading to cerebral parenchymal damage. In this article, we review definitions of carotid artery stiffness measures and pathophysiologic mechanisms underpinning its association with plaque development and downstream cerebral pathology. We will review the evidence surrounding the association of carotid stiffness measures with downstream manifestations including stroke, cerebral small vessel disease detected on brain MR such as white matter hyperintensities and covert brain infarctions, brain atrophy, and cognitive dysfunction. With consistent definitions, measurement methods, and further scientific support, carotid stiffness may have potential as an imaging-based risk factor for stroke and cognitive decline.

Optimal management of asymptomatic carotid stenosis in 2021: the jury is still out. An international, multispecialty, expert review and position statement.

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 was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. 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. 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.

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.

Asymptomatic Carotid Disease and Cognitive Impairment: What Is the Evidence?

The development of cognitive dysfunction and dementia is a complex, multifactorial process. One of the contributors to various types of cognitive dysfunction is carotid atherosclerosis which can frequently be seen in asymptomatic individuals. There are a number of different manifestations of asymptomatic carotid atherosclerosis including arterial stiffness, carotid intima-media thickening, flow-limiting stenosis, and complex, atherosclerotic plaque. Each of these forms of atherosclerosis may contribute to cerebral parenchymal damage, contributing to cognitive dysfunction. In this review article, we will discuss each of these forms of carotid atherosclerosis, present the potential mechanistic underpinnings behind an association, and then review the scientific evidence supporting potential associations to cognitive dysfunction and dementia.

Carotid Compliance and Parahippocampal and Hippocampal Volume over a 20-Year Period.

INTRODUCTION: We evaluated the association between carotid compliance, a measure of arterial stiffness, to parahippocampal volume (PHV) and hippocampal volume (HV) over 20 years later in the Atherosclerosis Risk in the Community study. METHODS: We included participants with common carotid compliance measurements at visit 1 (1987-1989) and volumetric brain MRI at visit 5 (2011-2013). The primary outcomes are pooled bilateral PHV and HV. We performed linear regression models adjusting for age, sex, vascular risk factors, and total brain volume. RESULTS: Of the 614 participants, higher compliance was correlated with higher PHV (R = 0.218[0.144-0.291], p < 0.001) and HV (R = 0.181 [0.105-0.255, p < 0.001]). The association was linear and significant after adjusting for confounders. At follow-up MRI, 30 patients with dementia had lower PHV and HV than patients without dementia (p < 0.001 and p < 0.001, respectively). CONCLUSION: Carotid compliance is associated with higher PHV and HV when measured 20 years later, further supporting the link between arterial stiffness and cognitive decline.