Extracranial Vascular Disease Research Articles

Principles Behind 4D Time-Resolved MRA/Dynamic MRA in Neurovascular Imaging

The abstract summarizes the evolution and role of dynamic magnetic resonance angiography (MRA) in neurovascular imaging. It highlights the historical context of neuroimaging, including the development of non-invasive techniques such as MRA. Different sequences of MRA, including time of flight (TOF), phase-contrast, contrast-enhanced, time-resolved, and dynamic MRA, are discussed, emphasizing their unique capabilities and clinical applications. Dynamic MRA, a four-dimensional imaging technique, offers high temporal and spatial resolution without ionizing radiation exposure, making it valuable for diagnosing cerebrovascular conditions like aneurysms, arteriovenous malformations (AVMs), dural arteriovenous fistulas (DAVF), steno-occlusive extracranial vascular disease, spinal vascular disease, neurovascular conflict, head and neck tumors, and cerebral venous sinus thrombosis (CVT). Comparative analyses with other imaging modalities, such as digital subtraction angiography (DSA), computed tomographic venography (CTV), and MR-based images, are presented, highlighting the diagnostic strengths and limitations of each technique. While DSA remains the gold standard, dynamic MRA shows promise as a non-invasive alternative with broad clinical utility. However, further large-scale prospective studies are needed to validate its diagnostic accuracy and establish its role in clinical practice.

Prevalence of Systemic Hypertension and the Effects of Cerebral Revascularization in Patients With Moyamoya Disease

Background Hypertension is often codiagnosed in patients with moyamoya disease (MMD), a progressive intracranial steno‐occlusive vasculopathy; this has principally been attributed to renal artery stenosis (up to 10%). Susceptibility MMD genes, including ring finger protein 213/mysterin and GUCY1A3 , have also been linked to extracranial vascular disease and increased systolic blood pressure. We aimed to define the prevalence of systemic hypertension in MMD patients and characterize its evolution after cerebral revascularization. Methods Patients with MMD treated with extracranial‐intracranial bypass from 2014 to 2018 were retrospectively enrolled. Blood pressure measurements and antihypertensive agent use were recorded pre‐ and postoperatively. Hypertension was defined according to the 2020 International Society of Hypertension Guidelines (adults) and 2017 American Academy of Pediatrics Guidelines (children). Multivariate logistic regression was performed for clinical and radiographic predictors of hypertension. Results A total of 242 adult and 51 pediatric patients underwent revascularization. Preoperatively, 146 adult and 20 pediatric patients met the diagnostic criteria for hypertension resulting in prevalences of 60.3% and 39.2% respectively. In adults, this was significantly associated with age (odds ratio [OR] 1.05 [95% CI, 1.02–1.09]), body mass index (OR, 1.08 [95% CI, 1.03–1.13]), hyperlipidemia (OR, 2.57 [95% CI, 1.09–6.04]), kidney disease (OR, 18.98 [95% CI, 1.80–200.47]), and symptomatic presentation (OR, 8.88 [95% CI, 1.16–68.06]). After a mean follow‐up of 34.3±18.1 months in adults (33.8±14.9 months – children), patients with hypertension decreased by 15.3% (1.9% – pediatrics) and 31.8% (17.7% – children) experienced improvement in hypertensive status with normalization of blood pressure or reduced need for antihypertensive agents. Posterior circulation involvement was a negative predictor for response of hypertensive status to revascularization (OR, 0.10 [95% CI, 0.01–0.79]). Conclusion Hypertension is prevalent among adult and pediatric patients with MMD with contributions from known vascular risk factors. Its association with symptomatic presentation and observed improvement following revascularization suggests blood pressure changes, in part, are a compensatory physiological response to increased intracranial vascular resistance.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol

IntroductionPositron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored....

Extracranial Vascular Malformations Increase Cardiovascular Disease Risk: A Nationwide Population-Based Cohort Study.

Extracranial vascular malformations affect vessel inflammation, clotting, and ischemia. However, the relationship between extracranial vascular malformations and myocardial infarction (MI) or stroke has not been fully elucidated. Limited studies have investigated the association between extracranial vascular malformations and cardiovascular diseases. A total of 48,701 patients with extracranial vascular malformations and a control cohort with 487,010 age- and sex-matched participants from the Korean National Health Insurance database were included. The incidence and risk of MI, ischemic stroke (IS), and hemorrhagic stroke (HS) between participants with extracranial vascular malformations and the control cohort was then compared. After adjusting for other cardiovascular disease risk factors, the adjusted hazard ratios (aHRs) for VMs, CMs, AVMs, and LMs in patients with acute MI were 1.25 [CI 1.04-1.50], 1.41 [CI 1.24-1.61], 1.68 [CI 1.18-2.37], and 1.40 [CI 1.31-1.48], respectively. For IS, the aHRs were 1.55 [CI 1.35-1.77], 1.92 [CI 1.74-2.11], 1.13 [CI 0.78-1.64], and 1.51 [CI 1.44-1.58], respectively. For HS, the aHRs were 1.51 [CI 1.12-2.05], 5.63 [CI 4.97-6.38], 2.93 [CI 1.82-4.72], and 1.34 [CI 1.20-1.50], respectively. Independent of cardiovascular risk factors, extracranial vascular malformations were associated with an increased risk of MI, IS, and HS. For patients with CMs and AVMs, intracerebral hemorrhage risk was particularly high, accounting for 563% and 293%, respectively. Therefore, even in patients with extracranial CMs or AVMs, performing diagnostic evaluations for cerebral AVMs and employing measures to prevent intracerebral hemorrhage are very crucial.

Extracranial Vascular Disease: Carotid Stenosis and Plaque Imaging.

Carotid atherosclerosis is an important contributor to ischemic stroke. When imaging carotid atherosclerosis, it is essential to describe both the degree of luminal stenosis and specific plaque characteristics because both are risk factors for cerebrovascular ischemia. Carotid atherosclerosis can be accurately assessed using multiple imaging techniques, including ultrasonography, computed tomography angiography, and magnetic resonance angiography. By understanding the underlying histopathology, the specific plaque characteristics on each of these imaging modalities can be appreciated. This article briefly describes some of the most commonly encountered plaque features, including plaque calcification, intraplaque hemorrhage, lipid-rich necrotic core, and plaque ulceration.

Vascular disease and multiple sclerosis: a post-mortem study exploring their relationships.

Vascular comorbidities have a deleterious impact on multiple sclerosis clinical outcomes but it is unclear whether this is mediated by an excess of extracranial vascular disease (i.e. atherosclerosis) and/or of cerebral small vessel disease or worse multiple sclerosis pathology. To address these questions, a study using a unique post-mortem cohort wherein whole body autopsy reports and brain tissue were available for interrogation was established. Whole body autopsy reports were used to develop a global score of systemic vascular disease that included aorta and coronary artery atheroma, cardiac hypertensive disease, myocardial infarction and ischaemic stroke. The score was applied to 85 multiple sclerosis cases (46 females, age range 39 to 84 years, median 62.0 years) and 68 control cases. Post-mortem brain material from a subset of the multiple sclerosis (n = 42; age range 39-84 years, median 61.5 years) and control (n = 39) cases was selected for detailed neuropathological study. For each case, formalin-fixed paraffin-embedded tissue from the frontal and occipital white matter, basal ganglia and pons was used to obtain a global cerebral small vessel disease score that captured the presence and/or severity of arteriolosclerosis, periarteriolar space dilatation, haemosiderin leakage, microinfarcts, and microbleeds. The extent of multiple sclerosis-related pathology (focal demyelination and inflammation) was characterized in the multiple sclerosis cases. Regression models were used to investigate the influence of disease status on systemic vascular disease and cerebral small vessel disease scores and, in the multiple sclerosis group, the relationship between multiple sclerosis-related pathology and both vascular scores. We show that: (i) systemic cardiovascular burden, and specifically atherosclerosis, is lower and cerebral small vessel disease is higher in multiple sclerosis cases that die at younger ages compared with control subjects; (ii) the association between systemic vascular disease and cerebral small vessel disease is stronger in patients with multiple sclerosis compared with control subjects; and (iii) periarteriolar changes, including periarteriolar space dilatation, haemosiderin deposition and inflammation, are key features of multiple sclerosis pathology outside the classic demyelinating lesion. Our data argue against a common primary trigger for atherosclerosis and multiple sclerosis but suggest that an excess burden of cerebral small vessel disease in multiple sclerosis may explain the link between vascular comorbidity and accelerated irreversibility disability.

MYOCARDIAL INFARCTION FROM EXTERNAL COMPRESSION OF THE OSTIAL LEFT MAIN CORONARY ARTERY IN A PATIENT WITH MOYAMOYA DISEASE

Extracranial vascular disease in patients with Moyamoya disease is increasingly recognized, with a wide spectrum of observed coronary artery pathology. A 54-year-old female with a history of bilateral internal carotid artery occlusion and ischemic strokes due to Moyamoya disease, left external

Rare variants in RNF213, a susceptibility gene for moyamoya disease, are found in patients with pulmonary hypertension and aggravate hypoxia-induced pulmonary hypertension in mice.

Ring finger 213 (RNF213) is a susceptibility gene for moyamoya disease (MMD), a progressive cerebrovascular disease. Recent studies suggest that RNF213 plays an important role not only in MMD, but also in extracranial vascular diseases, such as pulmonary hypertension (PH). In this study, we undertook genetic screening of RNF213 in patients with PH and performed functional analysis of an RNF213 variant using mouse models. Direct sequencing of the exons in the C-terminal region of RNF213, where MMD-associated mutations are highly clustered, and of the entire coding exons of BMPR2 and CAV1, the causative genes for PH, was performed in 27 Japanese patients with PH. Two MMD-associated rare variants (p.R4810K and p.A4399T) in RNF213 were identified in two patients, three BMPR2 mutations (p.Q92H, p.L198Rfs*4, and p.S930X) were found in three patients, whereas no CAV1 mutations were identified. To test the effect of the RNF213 variants on PH, vascular endothelial cell (EC)-specific Rnf213 mutant transgenic mice were exposed to hypoxia. Overexpression of the EC-specific Rnf213 mutant, but neither Rnf213 ablation nor EC-specific wild-type Rnf213 overexpression, aggravated the hypoxia-induced PH phenotype (high right ventricular pressure, right ventricular hypertrophy, and muscularization of pulmonary vessels). Under hypoxia, electron microscopy showed unique EC detachment in pulmonary vessels, and western blots demonstrated a significant reduction in caveolin-1 (encoded by CAV1), a key molecule involved in EC functions, in lungs of EC-specific Rnf213 mutant transgenic mice, suggestive of EC dysfunction. RNF213 appears to be a genetic risk factor for PH and could play a role in systemic vasculopathy.

Value of Eye Movement Examination in Aiding Precise Localization in Stroke

A 69-year-old black man with vascular risk factors, including hypertension, hyperlipidemia, and poorly controlled diabetes mellitus, who was treated with the vascular endothelial growth factor inhibitor, bevacizumab, for macular degeneration, experienced sudden onset horizontal diplopia associated with fatigue. His deficits did not prevent him from driving. The next morning he noticed right eye ptosis obscuring his vision. Because of worsening symptoms, the patient presented to the emergency department where he was found to have bilateral ptosis, right greater than left, and left internuclear ophthalmoplegia (INO). Pupils were equal and reactive to light. General neurological examination revealed peripheral neuropathy with decreased pinprick/light touch and vibration/joint position sense distally in the lower extremities with associated difficulty with tandem walk and positive Romberg sign. Initial National Institutes of Health Stroke Scale was 2 for partial gaze palsy and sensory deficits. He did not qualify for thrombolysis because of minor deficits and symptoms lasting longer than 4.5 hours. The patient was admitted to the neurology service with suspected stroke. MRI of the brain revealed a midbrain midline diffusion restriction with apparent diffusion coefficient correlate just ventral to the aqueduct of Sylvius slightly more extended to the right consistent with subacute ischemic stroke involving the nucleus of oculomotor nerve and adjacent medial longitudinal fasciculus (MLF) likely secondary to small-vessel disease. MR angiography of the head and neck did not show significant intracranial or extracranial vascular disease. Transthoracic echocardiogram revealed normal heart function and no patent foramen ovale. The patient was started on aspirin and a statin and provided an eye patch for comfort. His diplopia improved, and he was eventually discharged with follow-up with ophthalmology, balance rehabilitation clinic, and his primary care physician for management of his risk factors. This patient presented with acute onset painless horizontal diplopia and was found on examination to have …

Bone Subtraction 3-Dimension CT Angiography Using 64-Slice Multidetector CT for the Evaluation of Steno-Occlusive Intra- and Extracranial Vascular Diseases: Comparison with Digital Subtraction Angiography

CT angiography (CTA) is a noninvasive imaging method to detect arterial stenosis, cerebral aneurysm, and other vascular abnormalities. With the development of multidetector CT (MDCT) technology, the scan range and diagnostic accuracy of CTA has increased. But there are some limitations for the evaluation of intraand extracranial vascular diseases with conventional CTA technique. Separating vessels from the bone or perivascular calcifications can be difficult, particularly in areas such as the skull base (1). This limitation can be a barrier to its use in clinical practice. A further difficulty is that three dimenOriginal Article

VS09 MEDICAL MANAGEMENT OF EXTRACRANIAL VASCULAR DISEASE

Medical treatment is indicated for all patients with symptomatic or high‐risk asymptomatic extracranial vascular disease, whether or not a vascular intervention is planned or has been performed. Recent evidence mandates an aggressive approach to management of traditional vascular risk factors, frequently involving use of several medications concurrently such as angiotensin converting enzyme inhibitors, diuretics and statins. These treatments should be considered for all patients, including those with blood‐pressure and/or cholesterol measurements within what might be considered the “normal” range. However, treatment decisions should be tailored to individual patient circumstances. Vascular anatomical considerations must be taken into account, particularly the presence of severe bilateral internal carotid artery stenoses or occlusion. Combination antiplatelet therapy with aspirin plus dipyridamole is generally indicated for secondary prevention of cerebrovascular disease, whilst clopidogrel is used following stent placement. Advances in medical management of extracranial vascular disease which reduce the overall risk of cerebrovascular events have been introduced subsequent to some of the pivotal carotid surgery trials. Possible implications for surgical treatment decision‐making will be addressed.

Brain function monitoring during off pump cardiac surgery: the effect of cardiac output on cerebral perfusion in a patient with severe extracranial vascular disease

Zanatta, P.1; Valfrè, C.2; Bosco, E.1; Salandin, V.1; Sarpellon, M.1; Pinto, F.3 Author Information

Impact of duplex scanning on carotid endarterectomy

Duplex ultrasound permits safe and accurate assessment of the extracranial vasculature. This paper reports the change in patterns of referral to a specialized vascular unit following its introduction; increased referrals were seen in all specialties except neurology. A widely available and reliable duplex service has revealed more extracranial vascular disease than was previously recognized, and has increased referrals for carotid endarterectomy, thereby increasing surgical workload.

Assessment of CE-MRA for the rapid detection of supra-aortic vascular disease

Contrast-enhanced MR angiography (CE-MRA) using a combined head and neck coil permits non-invasive imaging of the vasculature from the aortic arch through to the Circle of Willis in less than 2 minutes. To determine the accuracy of CE-MRA for the detection of vascular pathology, in particular vascular stenoses, using digital subtraction angiography (DSA) as the gold standard. In a prospective study of 81 patients referred for DSA, CE-MRA and DSA studies were performed within 72 hours of each other. CE-MRA was performed on a 1.5 Tesla clinical MRI scanner using a five-channel neurovascular array (head and neck coil), with dynamic tracking of the IV gadolinium bolus. CE-MRAs and DSA films were read by two interventional neuroradiologists blinded to the clinical presentation of the patient. On DSA, there were 77 vascular stenoses > or =50% identified, 51 extracranial and 26 intracranial. The overall sensitivity of CE-MRA using the neurovascular array for the detection of vascular stenoses > or =50% was 57% (95% CI: 46 to 68%) with a specificity of 98% (97 to 99%). The sensitivity for the detection of extracranial vascular stenoses > or =50% was 82% (72 to 93%) with a specificity of 97% (96 to 98%). However, the sensitivity for the detection of intracranial vascular stenoses > or =50% was only 8% (0 to 18%), with a specificity of 99% (98 to 100%). At this stage Contrast-enhanced MR angiography using a neurovascular coil shows promise as a rapid, specific, and noninvasive screening method for extracranial vascular disease, but not for intracranial vascular disease.

Neuro-ophthalmology: examination and investigation

The detail to which a neuro-ophthalmological examination can be undertaken clearly depends on the facilities available to the examiner. Examination in a fully furnished ophthalmology suite is entirely different to...

Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats.

Although vascular dysregulation has been documented in patients with extracranial vascular disease, transient ischemic attacks, and stroke, the pathomechanisms are poorly understood. To model thromboembolic stroke in rats, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was used to generate a platelet thrombus in the carotid artery of anesthetized rats. After CCAT, platelet aggregates break off the thrombus, travel to the distal cerebral vasculature, damage blood vessels, and cause small infarctions. The authors hypothesized that deficits in the endothelial nitric oxide synthase (eNOS) pathway may be responsible for vascular dysfunction after embolic stroke. To examine the functional status of the eNOS system, they measured eNOS-dependent dilation after CCAT by applying acetylcholine through a cranial window over the middle cerebral artery. The authors also measured eNOS mRNA and protein in the middle cerebral artery to determine whether functional changes were caused by alterations in expression. eNOS-dependent dilation was reduced at 6 hours, elevated at 24 hours, and returned to baseline 72 hours after CCAT. Endothelial nitric oxide synthase mRNA increased at 2 hours and was followed by a rise in protein 24 hours after CCAT. Changes in the eNOS system may account for some of the observed vascular deficits in patients with cerebrovascular disease.

PTA Assisted Stenting for Extracranial Vascular Disease

We report 45 procedures in 43 patients with stenting for treatment of extracranial vascular disease. Lesions treated are supra-aortic extracranial arteries and jugular vein stenoses. There was no significant difference in the result of two stents (Palmaz or Wallstent) in our series. The stenting is feasible and relatively safe for treating traumatic aneurysm, stenosis or salvaging complications of PTA. Endovascular stent placement for supraaortic artery stenosis is evolving from its controversial position to that of an acceptable alternate treatment. The number of patients receiving supraaortic stent is growing worldwide despite the limit in design and availability of stents. The most common and widely used stents are Palmaz and Wallstent.

Imaging of extracranial occlusive vascular disease

The advantages, disadvantages, and cost-effectiveness of the imaging modalities used to diagnose extracranial occlusive vascular disease vary widely. The following article presents the characteristics and quality issues related to each imaging modality currently used to evaluate extracranial occlusive vascular disease. The purpose is to aid the surgeon in choosing or tailoring an imaging paradigm to maximize the quality of patient care in a cost-effective manner.

Surgical management of extracranial vertebral artery occlusive vascular diseases. Part I: Anatomy and pathophysiology

Atherosclerotic occlusive vascular disease does not affect the vertebrobasilar artery system as often as it does the carotid arteries. When the posterior circulation is affected, however, significant disability and death can result in many of the more advanced cases. In addition to atherosclerotic vascular disease, a number of other pathological conditions can also affect the vertebral arteries and conversely lead to extraluminal occlusive vascular disease and ischemia. The anatomy of the vertebral artery and vascular pathological conditions affecting this vessel are reviewed.

Surgical management of extracranial vertebral artery occlusive vascular diseases. Part II: Surgical strategies

During the last 50 years, the surgical management of extracranial vertebral artery occlusive vascular disease has evolved greatly. A select subset of patients previously unresponsive to medical therapies are now potential candidates for open or endovascular interventions. This article reviews surgical strategies for the treatment of these complex patients.