Results of Surgical Treatment of Aneurysmal Subarachnoid Hemorrhage in a Single Institution Over 12 Years.

OBJECTIVE: For patients with aneurysmal subarachnoid hemorrhage (aSAH) in whom endovascular treatment is not the optimal treatment strategy, microsurgical clipping remains a viable option. We examined changes in morbidity and outcome over time in patients treated surgically and in relation to surgeon volume and experience. METHODS: All patients who underwent microsurgery for aSAH from 2007 to 2019 at our institution were included. We compared technical complication rates and surgical outcomes between experienced (≥50 independent cases) and inexperienced (<50 independent cases) surgeons and between high-volume (≥20 cases/year) and low-volume (<20 cases/year) surgeons. RESULTS: Most of the 1,003 aneurysms (970 patients, median age 56 years) were in the middle cerebral (41.4%), anterior communicating (27.6%), and posterior communicating (17.5%) arteries; 46.5% were <7 mm. The technical complication rate was 7%, resulting in postoperative infarct in 4.9% of patients. Nineteen patients (2%) died within 30 days of admission. There were no significant changes in rates of technical complication, postoperative infarct, or mortality over the study period. There were no differences in postoperative infarction and technical complication rates between experienced and inexperienced surgeons (P = 0.28 and P = 0.05, respectively), but there were differences when comparing high-volume and low-volume surgeons (P = 0.03 and P < 0.001, respectively). The independent predictors of postoperative infarctions were aneurysm size (P = 0.001), intraoperative large-vessel injury (P < 0.001), and low surgeon volume (P = 0.03). CONCLUSIONS: We present real-world data on surgical morbidity and outcomes after aSAH. We demonstrated a relationship between surgeon volume and outcome for surgical treatment of aSAH, which supports the benefit of subspecialization in cerebrovascular surgery.

Evaluation of Outcomes Among Patients With Traumatic Intracranial Hypertension Treated With Decompressive Craniectomy vs Standard Medical Care at 24 Months: A Secondary Analysis of the RESCUEicp Randomized Clinical Trial.

Importance: Trials often assess primary outcomes of traumatic brain injury at 6 months. Longer-term data are needed to assess outcomes for patients receiving surgical vs medical treatment for traumatic intracranial hypertension. Objective: To evaluate 24-month outcomes for patients with traumatic intracranial hypertension treated with decompressive craniectomy or standard medical care. Design, Setting, and Participants: Prespecified secondary analysis of the Randomized Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) randomized clinical trial data was performed for patients with traumatic intracranial hypertension (>25 mm Hg) from 52 centers in 20 countries. Enrollment occurred between January 2004 and March 2014. Data were analyzed between 2018 and 2021. Eligibility criteria were age 10 to 65 years, traumatic brain injury (confirmed via computed tomography), intracranial pressure monitoring, and sustained and refractory elevated intracranial pressure for 1 to 12 hours despite pressure-controlling measures. Exclusion criteria were bilateral fixed and dilated pupils, bleeding diathesis, or unsurvivable injury. Interventions: Patients were randomly assigned 1:1 to receive a decompressive craniectomy with standard care (surgical group) or to ongoing medical treatment with the option to add barbiturate infusion (medical group). Main Outcomes and Measures: The primary outcome was measured with the 8-point Extended Glasgow Outcome Scale (1 indicates death and 8 denotes upper good recovery), and the 6- to 24-month outcome trajectory was examined. Results: This study enrolled 408 patients: 206 in the surgical group and 202 in the medical group. The mean (SD) age was 32.3 (13.2) and 34.8 (13.7) years, respectively, and the study population was predominantly male (165 [81.7%] and 156 [80.0%], respectively). At 24 months, patients in the surgical group had reduced mortality (61 [33.5%] vs 94 [54.0%]; absolute difference, -20.5 [95% CI, -30.8 to -10.2]) and higher rates of vegetative state (absolute difference, 4.3 [95% CI, 0.0 to 8.6]), lower or upper moderate disability (4.7 [-0.9 to 10.3] vs 2.8 [-4.2 to 9.8]), and lower or upper severe disability (2.2 [-5.4 to 9.8] vs 6.5 [1.8 to 11.2]; χ27 = 24.20, P = .001). For every 100 individuals treated surgically, 21 additional patients survived at 24 months; 4 were in a vegetative state, 2 had lower and 7 had upper severe disability, and 5 had lower and 3 had upper moderate disability, respectively. Rates of lower and upper good recovery were similar for the surgical and medical groups (20 [11.0%] vs 19 [10.9%]), and significant differences in net improvement (≥1 grade) were observed between 6 and 24 months (55 [30.0%] vs 25 [14.0%]; χ22 = 13.27, P = .001). Conclusions and Relevance: At 24 months, patients with surgically treated posttraumatic refractory intracranial hypertension had a sustained reduction in mortality and higher rates of vegetative state, severe disability, and moderate disability. Patients in the surgical group were more likely to improve over time vs patients in the medical group. Trial Registration: ISRCTN Identifier: 66202560.

What Factors Determine Treatment Outcome in Aneurysmal Subarachnoid Hemorrhage in the Modern Era? A Post Hoc STASH Analysis.

BACKGROUND: The management of aneurysmal subarachnoid hemorrhage (aSAH) has changed dramatically in the last few decades with the publication of a few major studies, including ISAT (International Subarachnoid Aneurysm Trial, the International Cooperative Study on the Timing of Aneurysm Surgery Study). The aim of this study is to analyze the outcome of patients with aSAH based on a contemporary series, identify the risk factors for poor outcome, and focus on patients with good-grade aSAH (to match the ISAT cohort). METHODS: Baseline demographic and outcome data (modified Rankin Scale) were available for the 803 patients recruited from the STASH (Simvastatin in Aneurysmal Subarachnoid Haemorrhage) trial for post hoc analysis, using a χ2 test or 2-sample t test. Logistic regression analysis was performed to assess the risk factors for poor outcome at 6 months. Propensity matched analysis comparing coiling and clipping, and subgroup analysis of good-grade patients (World Federation of Neurosurgical Societies grade I-II) were also performed. RESULTS: Logistic regression analysis showed that the treatment modality (i.e., coiling or clipping) was not associated with poor outcome at 6 months (P = 0.839). The risk factors associated with poor outcome at 6 months were poor admission World Federation of Neurosurgical Societies grade (P < 0.0001), Fisher grade on initial computed tomography scan (P = 0.013), and the development of delayed cerebral ischemia (P < 0.0001). Subgroup analysis for good-grade patients only showed that 82% of patients after coiling and 78% of patients after clipping were classed as good outcome at 6 months (P = 0.181). CONCLUSIONS: In the current era of aSAH management, apart from patients' admission status, SAH blood load and the development of delayed cerebral ischemia, treatment modality with either coiling or clipping was not associated with poor outcome difference at 6 months.

Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.

BACKGROUND: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG PET), [18F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES: This study tested the efficacy of gallium-68-labeled DOTATATE (68Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. METHODS: We confirmed 68Ga-DOTATATE binding in macrophages and excised carotid plaques. 68Ga-DOTATATE PET imaging was compared to [18F]FDG PET imaging in 42 patients with atherosclerosis. RESULTS: Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68Ga-DOTATATE ligand binding to SST2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68Ga-DOTATATE mTBRmax predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18F]FDG mTBRmax differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18F]FDG spillover rendered coronary [18F]FDG scans uninterpretable in 27 patients (64%). Coronary 68Ga-DOTATATE PET scans were readable in all patients. CONCLUSIONS: We validated 68Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188).

Pharmacologic Management of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) remains a condition with suboptimal functional outcomes, especially in the young population. Pharmacotherapy has an accepted role in several aspects of the disease and an emerging role in several others. No preventive pharmacologic interventions for SAH currently exist. Antiplatelet medications as well as anticoagulation have been used to prevent thromboembolic events after endovascular coiling. However, the main focus of pharmacologic treatment of SAH is the prevention of delayed cerebral ischemia (DCI). Currently the only evidence-based medical intervention is nimodipine. Other calcium channel blockers have been evaluated without convincing efficacy. Anti-inflammatory drugs such as statins have demonstrated early potential; however, they failed to provide significant evidence for the use in preventing DCI. Similar findings have been reported for magnesium, which showed potential in experimental studies and a phase 2 trial. Clazosentane, a potent endothelin receptor antagonist, did not translate to improve functional outcomes. Various other neuroprotective agents have been used to prevent DCI; however, the results have been, at best inconclusive. The prevention of DCI and improvement in functional outcome remain the goals of pharmacotherapy after the culprit lesion has been treated in aneurysmal SAH. Therefore, further research to elucidate the exact mechanisms by which DCI is propagated is clearly needed. In this article, we review the current pharmacologic approaches that have been evaluated in SAH and highlight the areas in which further research is needed.

Decompressive craniectomy: past, present and future.

Decompressive craniectomy (DC)--a surgical procedure that involves removal of part of the skull to accommodate brain swelling--has been used for many years in the management of patients with brain oedema and/or intracranial hypertension, but its place in contemporary practice remains controversial. Results from a recent trial showed that early (neuroprotective) DC was not superior to medical management in patients with diffuse traumatic brain injury. An ongoing trial is investigating the clinical and cost effectiveness of secondary DC as a last-tier therapy for post-traumatic refractory intracranial hypertension. With regard to ischaemic stroke (malignant middle cerebral artery infarction), a recent Cochrane review concluded that DC improves survival compared with medical management, but that a higher proportion of DC survivors experience moderately severe or severe disability. Although many patients have a good outcome, the issue of DC-related disability raises important ethical issues. As DC and subsequent cranioplasty are associated with a number of complications, indiscriminate use of this surgery is not appropriate. Here, we review the evidence and present considerations regarding surgical technique, ethics and cost-effectiveness of DC. Prospective clinical trials and cohort studies are essential to enable optimization of patient care and outcomes.

Fixed, dilated pupils following traumatic brain injury: historical perspectives, causes and ophthalmological sequelae.

Pupillary abnormalities are commonly seen in patients presenting with severe traumatic brain injury (TBI). The objectives of this study were to determine the underlying condition responsible, the natural history of recovery of third nerve palsy and the ultimate clinical outcome in 60 patients admitted to a regional neurosurgical centre with a diagnosis of TBI and unilateral or bilateral fixed, dilated pupils (FDP). In approximately three-quarters of cases, some form of road traffic incident was the mechanism of injury. In patients presenting with a unilateral FDP, the CT-defined condition was most commonly diffuse brain injury (49%) with no obvious lateralising condition. In 34% of cases CT demonstrated a lateralising condition ipsilateral to the side of the FDP and in 9% cases the FDP was contralateral to the side of the CT abnormality. Of those patients who survived an FDP, 72% were left with some form of ophthalmological deficit. Most patients with bilateral FDP did not survive (88%); however, of those who did survive, none was left in a persistent vegetative state or with any ophthalmological sequelae. A FDP is a grave prognostic sign following TBI commonly resulting in long term ophthalmological sequelae; however, a favourable outcome is still attainable.

Neurenteric cyst of the anterior cranial fossa: case report and literature review.

Intracranial neurenteric cysts are rare congenital lesions that typically occur in the posterior fossa. We report a case of a 70-year-old gentleman presenting with gait disturbance, found to have a neurenteric cyst primarily arising from and expanding the sella turcica. A review of the literature revealed 27 reports of supratentorial neurenteric cysts. Clinical presentation, radiological characteristics, treatment, prognosis and embryological origin are discussed. Intracranial neurenteric cysts should be included in the differential with any well-demarcated cystic lesion without enhancement on magnetic resonance imaging (MRI). Complete surgical excision is the treatment of choice, with good prognosis.

Causes of neurological deficits following clipping of 200 consecutive ruptured aneurysms in patients with good-grade aneurysmal subarachnoid haemorrhage.

BACKGROUND: The surgical risk of unruptured aneurysms is well quantified. Although the outcomes for ruptured aneurysms are also well described, due to the concurrent morbidity from the natural history of the haemorrhage, the relative contributions of surgery and natural history to outcome following aneurysmal subarachnoid haemorrhage (SAH) is not. Our aim was to quantify these risks. METHODS: This was a retrospective case note and radiological review of 200 patients with aneurysmal World Federation of Neurological Surgeons grade 1 or 2 SAH, treated with surgical clipping over a period of 3 years. Cases were reviewed to establish the incidence of surgical complications. Outcome was assessed at 3-month follow-up on Glasgow outcome score and the influence of surgical complications on this was assessed. RESULTS: Thirty-seven patients suffered a surgical complication (19%). Over one half (19/37) were due to a vascular injury and 13 of those resulted in an unfavourable outcome (7% of all operations). The remainder of the patients who suffered a surgical complication (18/37) included those with direct brain injury, cranial nerve injury, post-operative haematoma and bone flap infection. Of those, only two cases resulted in poor outcome (1% of operations). In total, 22 patients had an unfavourable outcome (11%). In 15 (8%), surgical complications were deemed the major contributory factor. CONCLUSIONS: Overall, surgically treated good-grade SAH has a good outcome. The majority of poor outcomes are due to surgical complications and most of these are vascular. Careful preservation of perforators and accurate clip placement remain the key factors in determining outcome in surgically treated good-grade SAH.

Improved cerebrovascular reactivity following low flow EC/IC bypass in patients with occlusive carotid disease.

Patients with major cerebral artery occlusive disease can suffer cerebral hypoperfusion and be at an increased risk of future strokes. EC/IC bypass has been shown to reduce this risk. Patients with cerebral hypoperfusion, and who are at risk of haemodynamic ischaemia, can be identified by the use of xenon computerised tomography (XeCT) to demonstrate severe impairment of the cerebrovascular reserve (CVR). We report our series on the effect of low flow EC/IC bypass on CVR in patients with symptomatic cerebral haemodynamic ischaemia. Thirteen patients with clinical and radiological features of cerebral hypoperfusion were assessed with acetazolamide activated XeCT. Pre- and postoperative regional cerebral blood flow (rCBF) and CVR were assessed. The change in CVR from pre- to post surgery was calculated (%CVR). Values were compared using ANOVA and Student's paired t-test. Unless otherwise stated, values are given as mean +/- standard error of the mean. Statistical significance was taken at p < 0.05. Pre-operative symptomatic hemisphere CBF was 38 +/- 2 mls/100g/min compared to 40 +/- 3.2 mls/100 g/min in the asymptomatic hemisphere, with the greatest difference observed in the MCA territory (38.6 +/- 2 cf 45.4 +/- 3.2 mls/100g/min). Baseline CBF was not significantly improved post EC/IC bypass. However CVR was significantly improved in the symptomatic hemisphere post-operatively (p = 0.015), with the greatest increase (28%) seen in the MCA territory (p = 0.0105). First, 85% of patients had either an improvement in symptoms or no further symptoms. There was a 93% graft patency and no operative mortality. Low flow EC/IC bypass can improve CVR in patients with symptomatic cerebral ischaemia in the presence of occlusive carotid disease. However, therapy must be individualised, with careful patient selection and minimal surgical morbidity.

Spinal intradural haemorrhage in a patient with Wegener's Granulomatosis.

We describe the case of a patient with known Wegener's Granulomatosis who developed a spontaneous intradural haematoma in the thoracic spine against a background of a recent relapse in her vasculitis. Decompression resulted in a rapid recovery of lower limb function. We propose involvement of the spinal meninges in the systemic vasculitis as the cause of haemorrhage.

Carotid artery stenosis-an evidence-based review of surgical and non-surgical treatments.

Carotid artery disease underlies a significant proportion of ischaemic strokes. Whilst secondary prevention by drug treatment is the first step in managing patients with known carotid stenoses, evidence from a number of large randomised controlled trials have clearly demonstrated a benefit for surgical treatment in symptomatic patients with moderate-to-severe stenosis. In asymptomatic patients with severe stenosis a benefit is conferred by surgery in selected patients. Carotid endarterectomy has formed the mainstay of surgical treatment. Endovascular angioplasty (with/without stenting) for carotid stenoses has been proposed as a viable or even superior alternative to carotid endarterectomy. The results from four large randomised controlled trials comparing the two modalities, considered together suggest a marginally better outcome for carotid endarterectomy compared with angioplasty in terms of perioperative mortality and stroke, though the results of further studies are awaited. For carotid surgery, a multi-centre randomised controlled trial evaluating the use of local anaesthesia versus general anaesthesia demonstrated no significant difference in outcome. Refinements in surgical technique such as patch angioplasty and intraluminal shunting provide equivocal benefit, with wide variation in their usage and in the results of studies evaluating them. More robust evidence supporting or refuting a benefit for these techniques is required.

The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease.

OBJECTIVES: The aim of this study was to evaluate the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on carotid plaque inflammation as determined by ultrasmall superparamagnetic iron oxide (USPIO)-enhanced carotid magnetic resonance imaging (MRI). The hypothesis was that treatment with 80 mg atorvastatin would demonstrate quantifiable changes in USPIO-enhanced MRI-defined inflammation within the first 3 months of therapy. BACKGROUND: Preliminary studies indicate that USPIO-enhanced MRI can identify macrophage infiltration in human carotid atheroma in vivo and hence may be a surrogate marker of plaque inflammation. METHODS: Forty-seven patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomly assigned in a balanced, double-blind manner to either 10 or 80 mg atorvastatin daily for 12 weeks. Baseline statin therapy was equivalent to 10 mg of atorvastatin or less. The primary end point was change from baseline in signal intensity (DeltaSI) on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks. RESULTS: Twenty patients completed 12 weeks of treatment in each group. A significant reduction from baseline in USPIO-defined inflammation was observed in the 80-mg group at both 6 weeks (DeltaSI 0.13; p = 0.0003) and at 12 weeks (DeltaSI 0.20; p < 0.0001). No difference was observed with the low-dose regimen. The 80-mg atorvastatin dose significantly reduced total cholesterol by 15% (p = 0.0003) and low-density lipoprotein cholesterol by 29% (p = 0.0001) at 12 weeks. CONCLUSIONS: Aggressive lipid-lowering therapy over a 3-month period is associated with significant reduction in USPIO-defined inflammation. USPIO-enhanced MRI methodology may be a useful imaging biomarker for the screening and assessment of therapeutic response to "anti-inflammatory" interventions in patients with atherosclerotic lesions. (Effects of Atorvastatin on Macrophage Activity and Plaque Inflammation Using Magnetic Resonance Imaging [ATHEROMA]; NCT00368589).

Microdialysis of cytokines: methodological considerations, scanning electron microscopy, and determination of relative recovery.

Cerebral microdialysis is a monitoring technique with expanding clinical and research utility following traumatic brain injury. This study's aim was to determine the relative recovery for 12 cytokines using both crystalloid (CNS perfusion fluid) and colloid (CNS perfusion fluid supplemented with 3.5% human serum albumin) perfusate. Six CMA71 microdialysis catheters (nominal molecular weight cut-off 100 kDa) were perfused in vitro with either crystalloid or colloid and the relative recovery (%) determined for the cytokines as follows (crystalloid/colloid perfusate): IL-1alpha (50.6/48), IL-1beta (34.6/38.4), IL-1ra (21.9/38.4), IL-2 (17.1/52.8), IL-4 (26/56.7), IL-6 (9.8/25.5), IL-8 (47.7/73.4), IL-10 (2.9/8.7), IL-17 (14.4/43.7), TNF-alpha (4.4/31.2), MIP-1alpha (31.8/55.6), and MIP-1beta (31.9/50.1). The colloid perfusate significantly improved relative recovery for nine of these cytokines ( p < 0.05), but not for IL-1alpha, IL-1beta, and IL-8. Relative recovery was related to apparent molecular weight of cytokine and to isoelectric point (pI), a surrogate marker of hydrophilicity. The mean fluid recovery for crystalloid and colloid perfusate was 92% and 145%, respectively. Scanning electron microscopy was utilized to investigate the ultrastructure of microdialysis membranes: (1) 20-kDa membrane, (2) 100-kDa membrane, and (3) ex vivo 100-kDa membrane. The 100-kDa membranes possessed multiple large cavities and the catheter examined after use in human brain clearly demonstrated cellular debris within the pores of the membrane. While colloid perfusate improves relative recovery, it causes a net influx of fluid into the microdialysis catheter, potentially dehydrating the extracellular space. This study is the first to systematically determine relative recovery in vitro for a wide range of cytokines. The two forms of perfusion fluid require direct comparison in vivo.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study.

BACKGROUND: Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. METHODS: 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi-sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. RESULTS: The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). CONCLUSIONS: Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease.

Structural analysis and magnetic resonance imaging predict plaque vulnerability: a study comparing symptomatic and asymptomatic individuals.

BACKGROUND: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. METHODS: Thirty non-consecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. RESULTS: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 +/- 193.1 vs 269.6 +/- 107.9 kPa; P = .004). CONCLUSIONS: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention.

A randomized trial of synthetic patch versus direct primary closure in carotid endarterectomy.

OBJECTIVE: To define whether or not direct microscopic closure with or without the use of a vascular patch is advantageous in terms of clinical outcome and late vessel occlusion rates after microsurgical carotid endarterectomy. METHODS: Three hundred thirty-eight elective carotid endarterectomies in 315 patients were randomized to direct arteriotomy or closure with a polyester collagen-coated vascular patch. Ten procedures did not follow the randomization process because of technical difficulties and were excluded. Vessel patency (duplex ultrasound) and outcome were assessed during and immediately after surgery and at 4 and 12 months after surgery. RESULTS: Four-month ultrasound assessment (n = 321) identified five occluded vessels: two in the patch group (n = 149) and three in the direct closure group (n = 172). Six patients in the patch group had died or were significantly disabled at 4 months, compared with five in the direct closure group. At the 12-month assessment (n = 313), eight vessels had occluded: five from the patched group (n = 146) and three from the direct closure group (n = 167). Eight patients in the patch group had died or were significantly disabled, compared with four in the direct closure group. No statistically significant difference between the two groups in terms of vessel occlusion, morbidity, or mortality was seen (P > 0.1). CONCLUSION: No difference in vessel patency and clinical outcome has been identified after microscopic patch angioplasty and direct arteriotomy repair. The authors conclude that there is no benefit from the routine use of patch angioplasty in microscopic carotid endarterectomy.

Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI.

BACKGROUND AND PURPOSE: It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. METHODS: Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. RESULTS: There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). CONCLUSIONS: This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages.

BACKGROUND: Inflammation within atherosclerotic lesions contributes to plaque instability and vulnerability to rupture. We set out to evaluate the use of a macrophage labeling agent to identify carotid plaque inflammation by in vivo magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty patients with symptomatic severe carotid stenosis scheduled for carotid endarterectomy underwent multi-sequence MRI of the carotid bifurcation before and after injection of ultrasmall superparamagnetic particles of iron oxide (USPIOs). USPIO particles accumulated in macrophages in 24 of 30 plaques (80%). Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in 24 of 27 (89%) patients, with an average reduction in signal intensity induced by the USPIO particles of 24% (range, 3.1% to 60.8%). CONCLUSIONS: USPIO-enhanced MRI can identify plaque inflammation in vivo by accumulation of USPIO within macrophages in carotid plaques.