Safety of endovascular treatment beyond the 6-h time window in 205 patients

Background and purpose Intra-arterial treatment (IAT) is effective when performed within 6 h of symptom onset in selected stroke patients (‘T < 6H’). Its safety and efficacy is unclear when the patient has had symptoms for more than 6 h (‘T > 6H’) or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. Methods Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0–2] or mortality 3 months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. Results Six-hundred and fifty-four patients were treated before (T < 6H) and 205 after 6 h or an unknown time (128 T > 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in T < 6H patients, vertebrobasilar occlusion was more common in T > 6H and UOS patients, and middle cerebral artery occlusions less common in T > 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. Conclusions Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6 h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.

No difference in anterior tibial translation with and without posterior cruciate ligament in less invasive total knee replacement

The relative advantages of cruciate retaining or cruciate resecting total knee replacement are still controversial. If the posterior cruciate ligament (PCL) is preserved, it should be properly balanced. In a previous study, it was demonstrated that increasing the flexion gap leads to an anterior translation of the tibia relative to the femur. Based on these results, we hypothesized that cutting the PCL increases the flexion gap and lessens anterior tibial translation.

Passing the thrombus in endovascular treatment of acute ischemic stroke: Do we penetrate the thrombus?

Mechanical thrombectomy is increasingly applied during the treatment of acute stroke. Various devices have been advocated with different sites of force effect at the thrombus. The purpose of this study was to evaluate the angiographic route of passing systematically and therefore to assess the site of deployment of mechanical devices in correlation to the thrombus in interventional stroke treatment. Twenty-one consecutive patients with endovascular treatment for acute ischemic stroke with 26 passing procedures were evaluated prospectively. Occlusion site was the M1-segment in 17 cases (65.4%), ICA termination in five cases (19.2%), M2-segment in two cases (7.7%), the A2-segment in one case (3.8%) and basilar artery in one case (3.8%). On angiographic images the microwire and microcatheter passage was evaluated by illustrating the entry point and course across the occlusion site in relation to the thrombus in different projections and in correlation to the recanalisation result. Results were correlated to the origin of the thrombi according to the TOAST criteria. In all cases the point of entry to the occlusion site was delineated laterally to the thrombus in at least one projection. The course of the wire across the occluded segment in relation to the thrombus was found to be laterally in 22 procedures (84.6%). In the majority of M1-occlusions (12/17, 70.6%) the passage was found in the cranial aspect of the thrombus. In four procedures (15.4%) angiograms in different projections did not unequivocally confirm a passage laterally to the thrombus. The route of passing the thrombus was independent of thrombus origin according to the TOAST criteria. In the majority of cases the complete route of passing the occlusion site was visualized angiographically. Entrance of the microwire and microcatheter at proximal surface of the thrombus takes place laterally to the thrombus and accordingly the passage takes place between the thrombus and the vessel wall independent of thrombus origin. A penetration of the thrombus was not observed. This route of passing has implications on deployment and transmission of force in relation to the thrombus in mechanical approaches and consequently on the development of retrieval devices.

Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development

VE-PTP, a receptor-type phosphotyrosine phosphatase, associates with the tyrosine kinase receptor Tie-2 and VE-cadherin and enhances the adhesive function of the latter. Here, VE-PTP was found to be restricted to endothelial cells, with a preference for arterial endothelium. Mutant mice expressing a truncated, secreted form of VE-PTP lacking the cytoplasmic and transmembrane domains and the most membrane-proximal extracellular fibronectin type III repeat, showed severe vascular malformations causing lethality at 10 days of gestation. Although blood vessels were initially formed, the intraembryonic vascular system soon deteriorated. Blood vessels in the yolk sac developed into dramatically enlarged cavities. In explant cultures of mutant allantoides, endothelial cells were found next to vessel structures growing as cell layers. No signs for enhanced endothelial apoptosis or proliferation were observed. Thus, the activity of VE-PTP is not required for the initial formation of blood vessels, yet it is essential for their maintenance and remodeling.

Reasons to withhold intra-arterial thrombolysis in clinical practice

BACKGROUND: In selected stroke centers intra-arterial thrombolysis (IAT) is used for the treatment of acute stroke patients presenting within 6 hours of symptom onset. However, data about eligibility of acute stroke patients for IAT in clinical practice are very scarce. METHODS: We collected prospectively data on indications advising for or against IAT of 230 consecutive stroke patients in a tertiary stroke center. RESULTS: 76 patients (33.0%) presented within 3 hours, 69 (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours. Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11 patients no or only peripheral branch occlusions were seen on arteriography and therefore IAT was not performed. In 9 patients the ICA was occluded and barred IAT and in five anatomical or technical difficulties made IAT impossible. 72 patients presenting within 6 hours did not undergo arteriography and thrombolysis, mostly because of mild (n = 44) or rapidly improving neurological deficits (n = 13). Other reasons to withhold IAT were CT and/or clinical findings suggesting lacunar stroke due to small vessel occlusion (n = 7), limiting comorbidty (n = 7) and baseline international normalized ratio > 1.7 (n = 1). CONCLUSIONS: A third of the patients underwent diagnostic arteriography and one fifth received IAT. The most important reasons to withhold thrombolysis were presentation beyond the 6 hours time window and mild or rapidly improving symptoms.

Lowered microvascular vessel wall oxygen consumption augments tissue pO2 during PgE1-induced vasodilation

Continuous infusion of intravenous prostaglandin E1 (PgE1, 2.5 mug/kg/min) was used to determine how vasodilation affects oxygen consumption of the microvascular wall and tissue pO(2) in the hamster window chamber model. While systemic measurements (mean arterial pressure and heart rate) and central blood gas measurements were not affected, PgE1 treatment caused arteriolar (64.6 +/- 25.1 microm) and venular diameter (71.9 +/- 29.5 microm) to rise to 1.15 +/- 0.21 and 1.06 +/- 0.19, respectively, relative to baseline. Arteriolar (3.2 x 10(-2) +/- 4.3 x 10(-2) nl/s) and venular flow (7.8 x 10(-3) +/- 1.1 x 10(-2)/s) increased to 1.65 +/- 0.93 and 1.32 +/- 0.72 relative to baseline. Interstitial tissue pO(2) was increased significantly from baseline (21 +/- 8 to 28 +/- 7 mmHg; P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the microvascular wall decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). The arteriolar vessel wall gradient, a measure of oxygen consumption by the vascular wall, decreased from 20 +/- 6 to 16 +/- 3 mmHg (P < 0.001). This reduction reflects a 20% decrease in oxygen consumption by the vessel wall and up to 50% when cylindrical geometry is considered. The venular vessel wall gradient decreased from 12 +/- 4 to 9 +/- 4 mmHg (P < 0.001). Thus PgE1-mediated vasodilation has a positive microvascular effect: enhancement of tissue perfusion by increasing flow and then augmentation of tissue oxygenation by reducing oxygen consumption by the microvascular wall.

New concept for CTO recanalization using controlled antegrade and retrograde subintimal tracking: the CART technique

OBJECTIVES: To demonstrate the safety and feasibility of a new concept for CTO recanalization using a controlled antegrade and retrograde subintimal tracking technique (CART technique). BACKGROUND: A successful percutaneous recanalization of chronic coronary occlusions results in improved survival, as well as enhanced left ventricular function, reduction in angina, and improved exercise tolerance. However, successful recanalization of CTOs is still not optimal, and needs further improvements. METHODS: Ten patients with a CTO underwent the CART procedure. This technique combines the simultaneous use of the antegrade and retrograde approaches. A subintimal dissection is created antegradely and retrogradely, which allows the operator to limit the extension of the subintimal dissection in the CTO portion. A retrograde approach means that the occlusion site is approached in a retrograde fashion through the best collateral channel from any other patent coronary artery. RESULTS: The occlusion site was located in the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to 84 months. Vessel recanalization was achieved in all patients. In all cases, the subintimal dissection was limited to the CTO region. No complications occurred in the collateral channel used for the retrograde approach. There were no in-hospital major adverse cardiac events. CONCLUSIONS: The CART technique is feasible, safe, and has a high success rate.

Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity

Pericyte loss and capillary regression are characteristic for incipient diabetic retinopathy. Pericyte recruitment is involved in vessel maturation, and ligand-receptor systems contributing to pericyte recruitment are survival factors for endothelial cells in pericyte-free in vitro systems. We studied pericyte recruitment in relation to the susceptibility toward hyperoxia-induced vascular remodeling using the pericyte reporter X-LacZ mouse and the mouse model of retinopathy of prematurity (ROP). Pericytes were found in close proximity to vessels, both during formation of the superficial and the deep capillary layers. When exposure of mice to the ROP was delayed by 24 h, i.e., after the deep retinal layer had formed [at postnatal (p) day 8], preretinal neovascularizations were substantially diminished at p18. Mice with a delayed ROP exposure had 50% reduced avascular zones. Formation of the deep capillary layers at p8 was associated with a combined up-regulation of angiopoietin-1 and PDGF-B, while VEGF was almost unchanged during the transition from a susceptible to a resistant capillary network. Inhibition of Tie-2 function either by soluble Tie-2 or by a sulindac analog, an inhibitor of Tie-2 phosphorylation, resensitized retinal vessels to neovascularizations due to a reduction of the deep capillary network. Inhibition of Tie-2 function had no effect on pericyte recruitment. Our data indicate that the final maturation of the retinal vasculature and its resistance to regressive signals such as hyperoxia depend on the completion of the multilayer structure, in particular the deep capillary layers, and are independent of the coverage by pericytes.

Impact of vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroup analysis of the SIRTAX trial

OBJECTIVES: We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization]). BACKGROUND: Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE). METHODS: A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter < or =2.75 vs. >2.75 mm). RESULTS: Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups. CONCLUSIONS: Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661).

Treatment of tibial fractures with plates using minimally invasive percutaneous osteosynthesis in dogs and cats

OBJECTIVES: The aim of the here described case series was to develop and evaluate the minimally invasive percutaneous osteosynthesis for the plate fixation of tibial fractures in dogs and cats. METHODS: Six dogs and four cats with shaft fractures of the tibia were treated using minimally invasive percutaneous osteosynthesis. Follow-up radiographs four to six weeks after fracture fixation were evaluated for fracture healing. For the long-term follow-up (minimum 2.4 years), owners were contacted by phone to complete a questionnaire. RESULTS: All fractures healed without the need for a second procedure. Follow-up radiographs obtained after four to six weeks in seven cases showed advanced bony healing with callus formation and filling of the fracture gaps with calcified tissue in all seven. All the patients had a good to excellent long-term result with full limb function. The time needed for regaining full limb use was two to three months. CLINICAL SIGNIFICANCE: Minimally invasive percutaneous osteosynthesis seems to be a useful technique for the treatment of tibial shaft fractures in dogs and cats.

Cerebral correlates of muscle tone fluctuations in restless legs syndrome: A pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography

BACKGROUND: The pathology of restless legs syndrome (RLS) is still not understood. To investigate the pathomechanism of the disorder further we recorded a surface electromyogram (EMG) of the anterior tibial muscle during functional magnetic resonance imaging (fMRI) in patients with idiopathic RLS. METHODS: Seven subjects with moderate to severe RLS were investigated in the present pilot study. Patients were lying supine in the scanner for over 50min and were instructed not to move voluntarily. Sensory leg discomfort (SLD) was evaluated on a 10-point Likert scale. For brain image analysis, an algorithm for the calculation of tonic EMG values was developed. RESULTS: We found a negative correlation of tonic EMG and SLD (p <0.01). This finding provides evidence for the clinical experience that RLS-related subjective leg discomfort increases during muscle relaxation at rest. In the fMRI analysis, the tonic EMG was associated with activation in motor and somatosensory pathways and also in some regions that are not primarily related to motor or somatosensory functions. CONCLUSIONS: By using a newly developed algorithm for the investigation of muscle tone-related changes in cerebral activity, we identified structures that are potentially involved in RLS pathology. Our method, with some modification, may also be suitable for the investigation of phasic muscle activity that occurs during periodic leg movements.

Closing the gap between coil and balloon in the neurointerventional armamentarium? Initial clinical experience with a nitinol vascular occlusion plug

INTRODUCTION: The use of vascular plug devices for the occlusion of high-flow lesions is a relatively new and successful procedure in peripheral and cardiopulmonary interventions. We report on the use and efficiency of the Amplatzer vascular plug in a small clinical series and discuss its potential for occlusion of large vessels and high-flow lesions in neurointerventions. METHODS: Between 2005 and 2007 four patients (mean age 38.5 years, range 16-62 years) were treated with the device, in three patients to achieve parent artery occlusion of the internal carotid artery, in one patient to occlude a high-flow arteriovenous fistula of the neck. The application, time to occlusion, and angiographic and clinical results and the follow-up were evaluated. RESULTS: Navigation, positioning and detachment of the device were satisfactory in all cases. No flow-related migration of the plug was seen. The cessation of flow was delayed by a mean of 10.5 min after deployment of the first device. In the procedures involving vessel sacrifice, two devices had to be deployed to achieve total occlusion. No patient experienced new neurological deficits; the 3-month follow-up revealed stable results. CONCLUSION: The Amplatzer vascular plug can be adapted for the treatment of high-flow lesions and parent artery occlusions in the head and neck. In this small series the use of the devices was uncomplicated and safe. The rigid and large delivery device and the delayed cessation of flow currently limit the device's use in neurointerventions.

Clinical validation of an automated vessel-segmentation software of the extracranial-carotid arteries based on 3D-MRA: A prospective study

OBJECTIVES: To determine the accuracy of automated vessel-segmentation software for vessel-diameter measurements based on three-dimensional contrast-enhanced magnetic resonance angiography (3D-MRA). METHOD: In 10 patients with high-grade carotid stenosis, automated measurements of both carotid arteries were obtained with 3D-MRA by two independent investigators and compared with manual measurements obtained by digital subtraction angiography (DSA) and 2D maximum-intensity projection (2D-MIP) based on MRA and duplex ultrasonography (US). In 42 patients undergoing carotid endarterectomy (CEA), intraoperative measurements (IOP) were compared with postoperative 3D-MRA and US. RESULTS: Mean interoperator variability was 8% for measurements by DSA and 11% by 2D-MIP, but there was no interoperator variability with the automated 3D-MRA analysis. Good correlations were found between DSA (standard of reference), manual 2D-MIP (rP=0.6) and automated 3D-MRA (rP=0.8). Excellent correlations were found between IOP, 3D-MRA (rP=0.93) and US (rP=0.83). CONCLUSION: Automated 3D-MRA-based vessel segmentation and quantification result in accurate measurements of extracerebral-vessel dimensions.

[Chronic anterior tibial syndrome]

In two young athletic men we made the diagnosis of chronic tibialis anterior syndrome. Pain during strenuous exercise was localized in the anterolateral aspect of both calves. After stopping exercise the complaints disappeared within 15-20 minutes and not in 2-3 minutes as it would be typical for patients with atherosclerotic peripheral arterial occlusive disease. Diagnosis is based on patient history, normal clinical examination (systolic ankle pressure determined by Doppler-Sonography, electronic segmental oscillography) and increased intramuscular pressure at rest (> 10 mmHg) and after exercise (42 and 35 mmHg). Bilateral fasciotomy was performed in both patients. They are free of pain after 3 respectively 6 months postoperatively.