Delayed posthypoxic leukoencephalopathy: a case series and review of the literature.

BACKGROUND: Delayed posthypoxic leukoencephalopathy (DPHL) is a rare and underrecognized entity where patients manifest a neurological relapse after initial recovery from an acute hypoxic episode. We sought to describe the magnetic resonance imaging (MRI) findings in a group of patients with DPHL and review the available literature. METHODS: Retrospective case series including patients who presented with neurological and/or psychiatric symptoms after recovery from an acute hypoxic episode. The history and clinical presentation were reviewed from the electronic medical records. MRI scans were evaluated from the picture archiving and communication system. We performed a comprehensive review of the English medical literature for prior published cases of DPHL and describe the key imaging findings that have been reported related to this condition. RESULTS: A total of five patients were identified, including four patients with respiratory failure due to drug overdoses from benzodiazepines, opioids, and/or barbiturates, and one patient who presented after cardiopulmonary arrest due to pulmonary embolism. All patients showed diffuse, extensive, and confluent white matter signal abnormalities including prominent restricted diffusion, extending to the subcortical white matter and respecting the U-fibers. There was no gyral edema or contrast enhancement. In one case histopathology was available, which highlighted patchy subcortical myelin loss with sparing of U-fibers and demonstrated prominent macrophage/microglial inflammation with extensive axonal damage. Of the other four patients, two were at their neurological baselines and two had persistent neurological deficits at the time of discharge. CONCLUSIONS: The described constellation of MRI findings is highly suggestive of DPHL in the appropriate clinical setting.

Carotid tortuosity in patients with prior cervical radiation: increased technical challenge during carotid stenting.

INTRODUCTION: Anatomic distortion associated with radiation-induced tissue changes may pose challenges for patients with prior cervical irradiation undergoing carotid stenting. We sought to evaluate the effect of these changes on carotid intervention. METHODS: Carotid angioplasty and stenting (CAS) for high-grade stenosis was performed in 203 patients. In all, 12 consecutive patients with prior ipsilateral cervical irradiation were age-/sex-matched to 24 controls. Degree of internal carotid (IC) tortuosity was assessed by 4 methods: (a) deviation of IC from common carotid (CCA) axis, (b) number of intersections between this axis and the course of the IC, (c) total degrees of angulation along the course of the extracranial IC, and (d) the IC length to straight-line distance ratio. RESULTS: Carotid angioplasty and stenting was successful in all patients. Mean age was 72.8 ± 10 years; 58.4% were male. Twenty-nine percent were symptomatic (14.4% transient ischemic attack [TIA], 8.5% cardiovascular accident [CVA], and 6.5% amaurosis). Comorbidities were similar between the entire cohort and the subgroups of irradiated/control patients. The IC revealed a higher degree of deviation from the axis of the CCA in the previously irradiated patients compared to those without radiation (29.2° ± 4.5° vs 13.0° ± 2.0°, P = .001) and was more likely to intersect this axis in those with a history of cervical irradiation (83.3% vs 14.3%, P < .05). Irradiated patients also exhibited a significantly greater degree of tortuosity versus nonirradiated patients when assessed by total angulation along the course of the carotid (171.8° ± 26.0° vs 74.2° ± 20.2°, P = .014) and by the IC length:distance ratio (1.14 ± 0.05 vs 1.04 ± 0.03, P = .020). Despite increased IC tortuosity in patients with prior irradiation, all procedures were successfully completed and there did not appear to be a predilection for a specific filter type. CONCLUSIONS: A history of cervical irradiation is associated with increased tortuosity of the IC, leading to potential challenges for filter and stent deployment. However, this increased procedural complexity did not affect technical success rate or device selection in this series.

Gene expression analysis of a porcine native abdominal aortic aneurysm model.

INTRODUCTION: We sought to characterize the gene expression patterns occurring during the development of aneurysms in the native porcine aorta. METHODS: In Yorkshire swine, the infrarenal aorta was balloon dilated and infused with a solution of type I collagenase/pancreatic porcine elastase (16,000 U/1,000 U). Aneurysmal and control aortic samples were obtained at 1 (n = 3), 2 (n = 6), and 4 (n = 5) weeks following aneurysm induction. RNA was isolated, converted to biotin-modified antisense RNA and hybridized to porcine genome arrays. Aneurysmal and control gene intensities were compared using the 2-sample-for-means z-test. P < .01 was considered statistically significant. RESULTS: Extracellular matrix remodeling genes that were upregulated in aneurysmal compared with control tissue included matrix metalloproteinase-1, -2, -3, and -9; MT-MMP; cathepsin-D, -H, -K, and -S; tissue inhibitor of metalloproteinase-1; and collagen I-alpha1 chain (P < .01). Elastin exhibited temporally downregulated gene expression (P < .01). Inflammatory genes that were upregulated included intercellular adhesion molecule-2, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-10, chemokine receptor-4, and tissue plasminogen activator (P < .01). Atherosclerosis and cancer genes that were upregulated included apolipoprotein E, acyl-CoA binding protein, friend leukemia virus integration-1, and E26 transformation-specific sequence (P < .01). CONCLUSION: The porcine model replicates the gene expression patterns that are observed during the development of aneurysms in human studies as well as in rodent models. The porcine model thereby represents a novel method to study the impact of endovascular, cell-based, and other therapeutic interventions on AAA pathophysiology.

Carotid angioplasty and stenting, success relies on appropriate patient selection.

OBJECTIVE: Carotid angioplasty and stenting (CAS) is a percutaneous alternative to carotid endarterectomy (CEA) for treating patients with carotid artery stenosis. This study sought to evaluate whether patients at increased perioperative risk for CEA may be treated with CAS while maintaining equivalent outcomes. METHODS: This study was a nonblinded, retrospective analysis of data obtained from September 2002 to present in the CAS group and from January 1997 to present in the CEA group. Two hundred thirty-one CAS and 647 CEA procedures were performed. Patients were selected for CAS based on criteria that placed them at increased risk for standard CEA surgery. Except for percentage women treated, baseline demographics did not differ between patients treated with CAS and CEA: mean age (72.0 years [range 46-94] vs 70.5 years [range 42-92], P = NS), mean follow-up (12.8 +/- 11.8 months vs 8.7 +/- 10.0 months, P = NS) and percentage women treated (41.4% vs 32.3%, P = .03). Cerebral protection devices were used in 228/231 patients treated with CAS, and each patient underwent an NIH Stroke Scale assessment 24 hours postoperatively and at 30 days follow-up by an independent observer. RESULTS: Preoperative neurologic symptoms did not differ between patients treated with CAS and CEA: amaurosis fugax (6.06% vs 6.96%, P = NS), transient ischemic attacks (13.4% vs 13.9%, P = NS), strokes (19.9% vs 14.1%, P = NS) and total symptoms (27.7% vs 30.5%, P = NS). Due to the selection of patient groups based on predefined clinical characteristics, factors associated with an increased risk of complications from standard CEA surgery were generally more prevalent in patients treated with CAS: neck irradiation (6.06% vs 1.24%, P < .001), neck dissection for cancer therapy (7.8% vs 1.5%, P < .001), prior ipsilateral CEA (15.2% vs 3.4%, P

Periprocedural complication rates are equivalent between symptomatic and asymptomatic patients undergoing carotid angioplasty and stenting.

Patients with neurologic symptoms who undergo carotid endarterectomy (CEA) have a higher incidence of stroke and death in the perioperative period than those with asymptomatic carotid disease. This study examines the outcomes of symptomatic and asymptomatic patients undergoing carotid stenting (CAS). From 2002 to 2006, 201 CAS procedures were performed in 193 patients (117 men, mean age 73 +/- 10 years), of whom 142 were for asymptomatic (AS) and 59 for symptomatic (S) disease. Preoperative neurologic symptoms included recent ipsilateral cerebrovascular accident (CVA, 29%), transient ischemic attack (50%), and amaurosis fugax (22%). There were 201 carotid stents placed (107 Acculink, 43 Wallstent, 23 Precise, 21 NexStent, 3 Exponent, 3 Xact, 1 Herculink) and 198 protection devices used (79 Accunet, 53 EPI Filterwire, 43 PercuSurge, 20 Angiogard, 3 EmboShield). Mean follow-up was 41 weeks. The groups were matched in terms of demographics and comorbidities (carotid artery disease, hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, smoking, and chronic obstructive pulmonary disease; p = nonsignificant [NS]). There was no significant difference in anatomic risk factors (neck irradiation, S 3%, AS 6%; prior CEA, S 14%, AS 14%; bovine arch, S 22%, AS 16%; p = NS), and the types of embolic protection devices and stents used were similar between groups. The mean percentages of preintervention carotid stenosis were equal (S 88%, AS 88%), and the technical success rate was 99%. Incidence rates of CVA (S 3.4%, AS 1.4%), myocardial infarction (S 1.7%, AS 1.4%), and death (S 0, AS 0.7%) were equivalent between groups (p = NS). CAS with cerebral protection can be performed safely in both symptomatic and asymptomatic patients. The presence of preoperative neurologic symptoms does not significantly increase the risk of adverse events in the perioperative period in this study.

Evaluation of pressure transmission and intra-aneurysmal contents after endovascular repair using the Trivascular Enovus expanded polytetrafluoroethylene stent graft in a canine model of abdominal aortic aneurysm.

OBJECTIVE: Endotension has been defined as persistently increased pressure within the excluded sac of an abdominal aortic aneurysm (AAA) resulting in increasing aneurysm size after endovascular repair in the absence of endoleak. Devices that use expanded polytetrafluoroethylene (ePTFE) have been associated with the development of endotension and continued AAA enlargement. In this study, intra-aneurysmal pressure and aneurysm content were evaluated after endovascular repair with the Enovus ePTFE stent graft in a canine model. METHODS: Prosthetic ePTFE aneurysms, each containing a solid-state, strain-gauge pressure transducer, were implanted in the infrarenal aorta of 13 mongrel dogs (25-35 kg). A second pressure transducer was inserted into the native aorta for systemic arterial pressure measurement. The stent graft was then deployed to exclude the aneurysm via distal aortic access. Comparison was made among three distinct stent grafts: the Trivascular Enovus (nonporous ePTFE; four animals), the original Gore Excluder (porous ePTFE; five animals), and the Medtronic AneuRx (Dacron; four animals). Daily systemic and intra-AAA pressures were measured for 4 weeks. Intra-aneurysmal pressures were indexed to simultaneously measured systemic pressures. After 4 weeks, the aorta, the prosthetic aneurysm, and its contents were harvested, photographed, and processed for histologic investigation with hematoxylin and eosin and Masson trichrome staining. RESULTS: Within 24 hours after exclusion, the mean arterial pressure and pulse pressure within the AAA sac tapered to less than 20% of systemic pressure for all three stent graft types. Throughout the postoperative period, significantly lower indexed intra-aneurysmal pressures were present in the Enovus- and AneuRx-treated aneurysms as compared with those treated with the original Excluder stent graft (0.05 +/- 0.04, 0.16 +/- 0.06, and 0.06 +/- 0.03 for the Enovus, Excluder, and AneuRx, respectively). Histologic analysis of the Enovus-treated aneurysms demonstrated intraluminal content characterized almost entirely by erythrocytes and infrequent white blood cells without the fibrin organization-characteristics of acute or chronic thrombus. This contrasted with the content of the Excluder-treated aneurysms, which contained poorly organized fibrin deposition suggestive of acute thrombus, and of the AneuRx-treated aneurysms, which demonstrated mature, well-organized collagenous connective tissue. CONCLUSIONS: Exclusion of the AAA with the Enovus stent graft resulted in nearly complete elimination of intra-aneurysmal pressure in this model. Histologic analysis of the aneurysm content further suggested complete exclusion, including elimination of circulating clotting factors and fibroblasts responsible for thrombus formation and reorganization. Ultimately, clinical evaluation will be necessary to demonstrate the effectiveness of this stent graft in preventing the development of endotension.

The creation of an infrarenal aneurysm within the native abdominal aorta of swine.

BACKGROUND: Models of native abdominal aortic aneurysms (AAA) have been created in rodents using elastase and calcium chloride perfusion. These models, however, do not permit the evaluation of endovascular devices. This study describes the use of mechanical and enzymatic techniques to create native AAA in swine. METHODS: Surgically exposed abdominal aortas of ten male Yorkshire swine (25-35 kg) were dilated, then perfused for 20 min with a 50-mL solution of elastase (30 units) and collagenase (8000 units). Serial magnetic resonance imaging (MRI) at 1, 3, and 6 wk was used to evaluate postoperative aortic diameter. Animals were euthanized at 24 h, 48 h and 1, 2, and 6 wk for histological evaluation. RESULTS: MRI demonstrated an increase in mean aortic diameter by 73.3% +/- 30.2% (33.3-116.7%), which gradually increased postoperatively. Partial endothelial loss, mural neutrophil infiltrate, and elastin disruption were evident (1, 3, and 7 days). Smooth muscle cell attrition occurred within the inner tunica media (7 days). Collagen deposition, limited SMC repopulation and luminal reendothelialization appeared at 3-6 wk. Elastin injury persisted. CONCLUSIONS: The creation of an infrarenal aneurysm is possible within the native aorta of swine. After aneurysm creation, progressive increase in aortic diameter was detectable. Further evaluation will be necessary to more completely characterize the nature and extent of elastase-induced porcine aortic aneurysmal degeneration.

The impact of increasing age on anatomic factors affecting carotid angioplasty and stenting.

PURPOSE: Current evaluations of carotid artery angioplasty and stenting (CAS) have suggested equivalency compared with carotid endarterectomy (CEA). However, the incidence of stroke and death with CAS may be higher in elderly patients. We assessed the anatomic characteristics of patients undergoing CAS and compared them based on age older or younger than 80 years. The impact of age on the incidence of postoperative complications was also determined. METHODS: From February 2003 to August 2005, 135 CAS procedures were performed in 133 patients. Digital subtraction angiograms for each patient were evaluated by two independent observers blinded to patient identifiers. Anatomic characteristics that impact the performance of CAS were assessed as either favorable or unfavorable. These included aortic arch elongation, arch calcification, arch vessel origin stenosis, common and internal carotid artery tortuosity, and treated lesion stenosis, calcification, and length. Postoperative events were defined as myocardial infarction, stroke, and death. Fisher's exact test and chi(2) tests were used to determine statistical significance (P < .05). RESULTS: Of the 133 patients treated, 87 (65%) were men and 46 (35%) were women; and 37 (28%) were >or=80 years of age. The cohort >or=80 years old had an increased incidence of unfavorable arch elongation (P = .008), arch calcification (P = .003), common carotid or innominate artery origin stenosis (P = .006), common carotid artery tortuosity (P = .0009), internal carotid artery tortuosity (P = .019), and treated lesion stenosis (P = .007). No significant difference was found for treated lesion calcification or length. Perioperative cerebral vascular accidents occurred in four patients (3.0%, 3 with no residual deficit, 1 with residual deficit), myocardial infarction in three (2.2%), and one patient (0.8%) died secondary to a hemorrhagic stroke. The combined stroke, myocardial infarction, and death rate for the entire population was 3.7%. The rate was significantly increased in patients aged >or=80 years old (10.8%) compared with those aged <80 years old (1%, P = .012). CONCLUSIONS: Elderly patients, defined as those aged >80 years, have a higher incidence of anatomy that increases the technical difficulty of performing CAS. This increase in unfavorable anatomy may be associated with complications during CAS. Although the small number of perioperative events does not allow for determination of a direct relationship with specific anatomic characteristics, the presence of unfavorable anatomy does warrant serious consideration during evaluation for CAS in elderly patients.

Characterization of endoleak following endovascular repair of abdominal aortic aneurysms.

Aneurysm models have been developed to study the pathobiology of abdominal aortic aneurysm and to evaluate the efficacy of endovascular therapy. The purpose of this review is to describe the use and limitations of current animal and experimental models for the characterization of endoleak following endovascular repair of abdominal aortic aneurysms.

Determining the quantity and character of carotid artery embolic debris by electron microscopy and energy dispersive spectroscopy.

OBJECTIVES: Carotid artery angioplasty and stenting (CAS) is now routinely performed with embolic protection devices, yet little is known about the compositional characteristics of the captured embolic debris and whether the type or quantity of debris correlates with patient, lesion, or operator characteristics. This study examined the embolic debris generated during CAS using electron microscopy and energy dispersive spectroscopy (EDS) for symptomatic and asymptomatic patients. METHODS: Between 2003 and 2005, CAS for carotid stenosis was performed in 175 patients. Cerebral protection devices were used in all but three cases. Sixty-four consecutive unselected microporous filters from procedures performed by a single vascular surgeon were obtained for analysis. Captured particulate debris within the protection devices was quantified (number and mean size of particles) by light microscopy for all filters. Twenty protection devices (9 symptomatic, 11 asymptomatic patients) were processed for electron microscopy and EDS to assess morphology, cellular composition, and calcium content of debris. RESULTS: Captured particulate matter was present in 49 filters (77%) and included particles measuring 200 to 500 mum in 72%, 500 to 1000 mum in 53%, and >1000 mum in 33%. The mean number of captured particles was 6.9, and mean size was 248 +/- 150 mum. Univariate analysis revealed that sequential patient cohort and filter type were correlated with the number (but not size) of captured particles. The number of particles significantly decreased after the first cohort of 20 patients (11.5 particles) compared with the second (5.0 particles, P = .023) and third (5.2 particles, P = .029) cohorts. The type of captured debris ranged from sheets of damaged red blood cells without other components to clumps of recently activated platelets with early fibrin crosslinking to plaque debris coated with well-organized coalescing areas of platelet thrombus. Platelet activation was more common in symptomatic patients (78%) than asymptomatic patients (27%; P < .05). Despite the presence of calcified lesions in six patients whose filters were analyzed by EDS, <1% of energy emission on EDS of scanned particulate debris fell within the emission range of calcium, indicating the presence of minimal calcium in the embolic particles. CONCLUSIONS: Particulate embolic debris is released in most patients during CAS and can measure >1000 mum in one third of patients. The number of particles may decrease with increasing operator experience with CAS. Debris captured during CAS with embolic protection exhibits a range of cellular and acellular components on electron microscopy, with a higher prevalence of platelet activation evident in symptomatic patients.

Models of abdominal aortic aneurysm: characterization and clinical applications.

Abdominal aortic aneurysms (AAAs) are responsible for considerable morbidity, mortality, and cost to society. The pathogenesis of AAA formation, however, remains poorly understood. Animal models have been used in a range of experiments designed to provide further objective scientific assessment of the pathogenesis as well as the treatment of AAA. The purpose of this manuscript is to review the current models of AAA and their potential clinical implications.

Evaluation of the accuracy of a wireless pressure sensor in a canine model of retrograde-collateral (type II) endoleak and correlation with histologic analysis.

BACKGROUND: The utility of intra-aneurysmal pressure determination is dependent on the ability to measure pressure in the presence of endoleak and thrombosis. In this study, the accuracy of a CardioMEMS wireless pressure sensor (CardioMEMS, Atlanta, Ga) transducer in the presence of thrombus associated with type II endoleak was measured. METHODS: Type II endoleaks were created in four mongrel dogs by implanting four collateral arterial side branches (lumbar and caudal mesenteric arteries) as a Carrel patch onto a 3-cm prosthetic polytetrafluoroethylene abdominal aortic aneurysm (AAA). The aneurysm was excluded 2 weeks later from antegrade perfusion by a stent graft. The wireless pressure sensor was positioned in the AAA external to the stent graft. A Konigsberg intraluminal solid-state strain-gauge pressure transducer (Konigsberg Instruments, Pasadena, Calif) that is accurate in the presence of thrombus served as the control to determine AAA pressure. Both of the transducers were implanted on the luminal surface of the aneurysm, 180 degrees opposite from the Carrel patch and endoleak channel. Intra-aneurysmal pressure resulting from the type II endoleak was measured twice daily for 4 weeks using both transducers. A total of 56 pre-exclusion and 224 post-exclusion distinct pressure determinations were made. Intra-aneurysmal pressure was indexed to the systemic pressure that was simultaneously measured by a strain-gauge pressure transducer implanted in the native aorta. Histologic analysis of the aneurysm contents was performed with hematoxylin and eosin. RESULTS: The intra-aneurysmal systolic, mean, and pulse pressures produced by the type II endoleak were significantly lower than systemic pressure in all animals and were < 60% of systemic pressure (P < .001). Close correlation between the wireless transducer and the control strain-gauge transducer was observed (R = 0.83, P < .001). Arteriography and Doppler ultrasound documented retrograde flow through the aneurysm side branches and persistent endoleak patency up to the time of euthanasia. Pathologic analysis demonstrated the endoleak channel to be patent and separated from the transducers by thrombus, which surrounded both transducers. CONCLUSIONS: Intra-aneurysmal pressure generated by type II endoleaks may be accurately measured through thrombus using a wireless pressure sensor in the canine model. The wireless sensor has the potential for clinical applicability in diagnosing and characterizing type II endoleaks.

Safety and efficacy of carotid angioplasty and stenting in high-risk patients.

Performance of carotid endarterectomy (CEA) may be associated with an increased risk in patients with significant comorbid medical conditions, neck irradiation, or previous CEA. This study compared the results of CEA with carotid angioplasty and stenting (CAS) in high-risk patients treated for carotid stenosis. Five hundred forty-five patients who underwent CEA and 148 patients who underwent CAS were evaluated. For patients undergoing CEA, general anesthesia was used in 91 per cent, electroencephalographic monitoring was used in 63 per cent, and shunting was performed in 19.8 per cent. Cerebral protection devices were used in 145/148 of CAS cases, and self-expanding stents were used in all cases. Evaluated end points included major cardiovascular events, and a composite of death, stroke, or myocardial infarction for the duration of the follow-up. Mean follow-up was 18 months for CAS and 23 months for CEA. Significant differences were present in patient age (CAS, 75 +/- 11.0 years vs CEA, 71 +/- 9 years, P = 0.012), however, there were no significant differences (P = NS) in gender or smoking history. The mean modified Goldman Score was significantly higher for CAS (21.1 +/- 14.8 [95% confidence interval = 18, 24]) than for CEA (6.3 +/- 6.8 [95% confidence interval = 5.7, 6.9]; P = 0.0001) patients. The incidence of periprocedural complications did not vary significantly between patients treated with CAS (CVA, 1.4%; myocardial infarction [MI], 1.4%; death, 0.7%; CVA/MI/death, 3.4%) compared with CEA (CVA, 1.8%; MI, 1.1%; death, 0.4%; CVA/MI/death, 4.0%). CAS is equivalent to CEA in safety and efficacy, even when performed in patients who may be at increased surgical risk.

Analysis of outcomes following failed endovascular treatment of chronic limb ischemia.

Despite recent studies highlighting the advantages of endoluminal intervention in the management of chronic limb ischemia (CLI), outcomes following failed peripheral angioplasty remain less well described. We present a retrospective analysis of failed transluminal infrainguinal percutaneous arterial angioplasty with or without stenting (PTA/S) in patients with CLI. A database of patients undergoing infrainguinal PTA/S between 2002 and 2005 was maintained. Patients underwent duplex scanning follow-up at 2 weeks, 3 months, and every 6 months after the intervention. Angiograms were reviewed in all cases to assess lesion characteristics. Results were standardized to current Transatlantic Inter-Society Consensus (TASC) criteria. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. In total, our analysis involved 246 patients who underwent treatment for CLI using PTA/S. Eighteen percent of procedures (n = 46) were considered an intervention failure secondary to restenosis by duplex ultrasound, returning clinical symptoms, a nonhealing foot lesion, or the absence of a prior palpable pulse. Indications for the original procedure in patients whose PTA/S failed were tissue loss in 44%, claudication in 44%, and rest pain in 12%, while TASC lesion grades were A (0%), B (18%), C (18%), and D (64%). Of patients failing PTA/S, 4% failed in the first 30 days, 78% failed between 1 and 18 months, while 18% failed following 18 months, with a mean time to failure of 8.7 months. Also, 82% of PTA/S failures were candidates for a second endovascular procedure, 11% were suitable for only traditional open bypass, and 4% demonstrated progression of disease necessitating amputation. Of patients undergoing a second endovascular procedure, limb salvage rates were 86% at 12-month follow-up and there was a single periprocedural mortality and complication rate of 6.6%. Of patients requiring open surgical bypass after failed PTA/S, 20% (n = 1) required a major amputation and there were no mortalities. Failure of endoluminal therapy for treatment of lower extremity arterial occlusive disease is amenable to subsequent endovascular intervention for limb salvage with limited morbidity and mortality.