Daniel A. Rüfenacht

Vertebroplasty: Clinical Experience and Follow-Up Results

This study was undertaken to report the clinical experience with percutaneous minimal invasive vertebroplasty using polymethyl-methacrylcate (PMMA) for a consecutive group of patients. Over the period of the last 4 years, 40 patients were treated at 68 vertebral segment levels with the intention to relieve pain related to vertebral body lesions. Reduced vertebral body height and destruction of the posterior vertebral wall were not considered to be exclusion criterias. The vertebroplasty procedure was performed under general anesthesia and in prone position with imaging control using mostly biplane DSA fluoroscopic guidance, and rarely with single-plane mobile DSA combined with computed tomographic guidance. Unilateral, but more frequently bilateral, transpedicular introduction of a 2-3-mm OD needle was followed by an injection of polymethyl-methacrylcate (PMMA). PMMA preparation involved a diluted mixture (20 mL powder for 5 mL liquid) allowing for an extended polymerization time of up to 8 min. The PMMA was mixed with metallic powder to enhance its radio-opacity. Before PMMA injection, a vertebral phlebography was obtained to evaluate the filling pattern and identify sites of potential PMMA leakage. Injection of opacified PMMA was performed under continuous visual control with fluoroscopy to obtain adequate filling and to avoid important PMMA leakage. Clinical follow-up involved an evaluation using a questionnaire for assessment of pain, pain medication, and mobility. One to six levels were treated in one to three treatment sessions for patients with metastatic, osteoporotic, and hemangiomatous lesions of the vertebral bodies who presented with pain. The results observed matched those reported previously with a success rate of approximately 80% and a complication rate below 6% per treated level. Treatment failure and complications observed were related to leakage, insufficient pretreatment evaluation, anesthesia, or patient position during treatment. Image guidance with fluoroscopy was efficient both for precise transpedicular approach and PMMA implantation control. Vertebroplasty is very efficient for treatment of pain. Treatment failure was mostly related to insufficient pretreatment clinical evaluation, and complication due to excessive PMMA volume injection. Control of PMMA volume seems to be the most critical point for avoiding complications. A good fluoroscopy control is therefore mandatory.

Genome-wide association study of intracranial aneurysm identifies three new risk loci

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with ∼832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10−12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10−9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10−9). We also confirmed prior associations near SOX17 (8q11.23–q12.1; OR = 1.28, P = 1.3 × 10−12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10−22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model - A report on the Virtual Intracranial Stenting Challenge 2007

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

Pathology Findings With Acrylic Implants

We report the pathological findings in cases of acrylic implants obtained by direct intratumoral injection of polymethyl-methacrylate (PMMA) and N-butyl-cyano-acrylate (NBCA). Direct intratumoral injection of acrylic implants was performed for a variety of primary and secondary bone lesions. These types of treatments have been used at our institution in the last 4 years for 40 vertebroplasty (PMMA) procedures and for nine bone lesions of other locations (PMMA, NBCA). Postmortem histology became available for 1 case of PMMA and for 5 cases with NBCA intratumoral acrylic implants. The pathological findings associated with PMMA and NBCA were evaluated and compared. PMMA exhibited a macroscopic and microscopic rim of tumor necrosis, 6 months after implantation. NBCA exhibited compressive effects on the nearby tumor tissue, however, without signs of significant necrosis outside the acrylic tumor cast. Tumor captured inside the acrylic cast showed extensive to near complete necrosis. Acrylic implants may lead to necrosis when injected directly in tumors. The necrotizing effect may extend beyond the limits of an implant in the case of PMMA. Such an extended effect of PMMA, when compared with NBCA, may be due to the variable toxicity of acrylic implants, including the different degrees of the exothermic reaction during polymerization.

Effect of aging on elastin functionality in human cerebral arteries

Background and Purpose— Aging affects elastin, a key component of the arterial wall integrity and functionality. Elastin degradation in cerebral vessels is associated with cerebrovascular disease. The goal of this study is to assess the biomechanical properties of human cerebral arteries, their composition, and their geometry, with particular focus on the functional alteration of elastin attributable to aging. Methods— Twelve posterior cranial arteries obtained from human cadavers of 2 different age groups were compared morphologically and tested biomechanically before and after enzymatic degradation of elastin. Light, confocal, and scanning electron microscopy were used to analyze and determine structural differences, potentially attributed to aging. Results— Aging affects structural morphology and the mechanical properties of intracranial arteries. In contrast to main systemic arteries, intima and media thicken while outer diameter remains relatively constant with age, leading to concentric hypertrophy. The structural morphology of elastin changed from a fiber network oriented primarily in the circumferential direction to a more heterogeneously oriented fiber mesh, especially at the intima. Biomechanically, cerebral arteries stiffen with age and lose compliance in the elastin dominated regime. Enzymatic degradation of elastin led to loss in compliance and stiffening in the young group but did not affect the structural and material properties in the older group, suggesting that elastin, though present in equal quantities in the old group, becomes dysfunctional with aging. Conclusions— Elastin loses its functionality in cerebral arteries with aging, leading to stiffer less compliant arteries. The area fraction of elastin remained, however, fairly constant. The loss of functionality may thus be attributed to fragmentation and structural reorganization of elastin occurring with age.

The POST trial: initial post-market experience of the Penumbra system: revascularization of large vessel occlusion in acute ischemic stroke in the United States and Europe

Background and purpose The purpose of this study was to assess the initial post-market experience of the device and how it is compared with the Penumbra Pivotal trial used to support the 510k application. Methods A retrospective case review of 157 consecutive patients treated with the Penumbra system at seven international centers was performed. Primary endpoints were revascularization of the target vessel (TIMI score of 2 or 3), good functional outcome as defined by a modified Rankin scale (mRS) score of ≤2 and incidence of procedural serious adverse events. Results were compared with those of the Penumbra pivotal trial. Results A total of 157 vessels were treated. Mean baseline values at enrollment were: age 65 years, NIHSS score 16. After use of the Penumbra system, 87% of the treated vessels were revascularized to TIMI 2 (54%) or 3 (33%) as compared with 82% reported in the Pivotal trial. Nine procedural serious adverse events were reported in 157 patients (5.7%). All-cause mortality was 20% (32/157), and 41% had a mRS of ≤2 at 90-day follow-up as compared with only 25% in the Pivotal trial. Patients who were successfully revascularized by the Penumbra system had significantly better outcomes than those who were not. Conclusion Initial post-market experience of the Penumbra system revealed that the revascularization rate and safety profile of the device are comparable to those reported in the Pivotal trial. However, the proportion of patients who had good functional outcome was higher than expected.

The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia

We investigated the use of in situ implant formation that incorporates superparamagnetic iron oxide nanoparticles (SPIONs) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. We developed injectable formulations that form gels entrapping magnetic particles into a tumor. We used SPIONs embedded in silica microparticles to favor syringeability and incorporated the highest proportion possible to allow large heating capacities. Hydrogel, single-solvent organogel and cosolvent (low-toxicity hydrophilic solvent) organogel formulations were injected into human cancer tumors xenografted in mice. The thermoreversible hydrogels (poloxamer, chitosan), which accommodated 20% w/v of the magnetic microparticles, proved to be inadequate. Alginate hydrogels, however, incorporated 10% w/v of the magnetic microparticles, and the external gelation led to strong implants localizing to the tumor periphery, whereas internal gelation failed in situ. The organogel formulations, which consisted of precipitating polymers dissolved in single organic solvents, displayed various microstructures. A 8% poly(ethylene-vinyl alcohol) in DMSO containing 40% w/v of magnetic microparticles formed the most suitable implants in terms of tumor casting and heat delivery. Importantly, it is of great clinical interest to develop cosolvent formulations with up to 20% w/v of magnetic microparticles that show reduced toxicity and centered tumor implantation.

Parenchymal abnormalities associated with developmental venous anomalies

IntroductionTo report a retrospective series of 84 cerebral developmental venous anomalies (DVAs), focusing on associated parenchymal abnormalities within the drainage territory of the DVA.MethodsDVAs were identified during routine diagnostic radiological work-up based on magnetic resonance imaging (MRI) (60 cases), computed tomography (CT) (62 cases) or both (36 cases). Regional parenchymal modifications within the drainage territory of the DVA, such as cortical or subcortical atrophy, white matter density or signal alterations, dystrophic calcifications, presence of haemorrhage or a cavernous-like vascular malformation (CVM), were noted. A stenosis of the collecting vein of the DVA was also sought for.ResultsBrain abnormalities within the drainage territory of a DVA were encountered in 65.4% of the cases. Locoregional brain atrophy occurred in 29.7% of the cases, followed by white matter lesions in 28.3% of MRI investigations and 19.3% of CT investigations, CVMs in 13.3% of MRI investigations and dystrophic calcification in 9.6% of CT investigations. An intracranial haemorrhage possibly related to a DVA occurred in 2.4% cases, and a stenosis on the collecting vein was documented in 13.1% of cases. Parenchymal abnormalities were identified for all DVA sizes.ConclusionBrain parenchymal abnormalities were associated with DVAs in close to two thirds of the cases evaluated. These abnormalities are thought to occur secondarily, likely during post-natal life, as a result of chronic venous hypertension. Outflow obstruction, progressive thickening of the walls of the DVA and their morphological organization into a venous convergence zone are thought to contribute to the development of venous hypertension in DVA.

Effect of Flow Diverter Porosity on Intraaneurysmal Blood Flow

AbstractBackground and Purpose:Growth and rupture, the two events that dominate the evolution of an intracranial aneurysm, are both dependent on intraaneurysmal flow. Decrease of intraaneurysmal flow is considered an attractive alternative for treating intracranial aneurysms by minimally invasive techniques. Such modification can be achieved by inserting stents or flow diverters alone. In the present paper, the effect of different commercial and innovative flow diverters’ porosity was studied in intracranial aneurysm models.Material and Methods:Single and stent-in-stent combination of Neuroform II as well as single and stent-in-stent combination of a new innovative, low-porosity, intracranial stent device (D1, D2, D1 + D2) were inserted in models of intracranial aneurysms under shear-driven flow and inertia-driven flow configurations. Steady and pulsating flow rates were applied using a blood-like fluid. Particle image velocimetry was used to measure velocity vector fields in the aneurysm midplane along the vessel axis. Flow and vorticity patterns, velocity and vorticity magnitudes were quantified and their value compared with the same flows in absence of the flow diverter.Results:In absence of flow diverters, a solid-like rotation could be observed in both shear-driven and inertia-driven models under steady and pulsatile flow conditions. The flow effects due to the insertion of low-porous devices such as D1 or D2 provoked a complete alteration of the flow patterns and massive reduction of velocity or vorticity magnitudes, whereas the introduction of clinically adopted high-porous devices provoked less effect in the aneurysm cavity. As expected, results showed that the lower the porosity the larger the reduction in velocity and vorticity within the aneurysm cavity. The lowest-porosity device combination (D1 and D2) reached an averaged reduction of flow parameters of 80% and 88% under steady and pulsatile flow conditions, respectively. The reduction in mean velocity and vorticity was much more significant in the shear-driven flows as compared to the inertia-driven flows.Conclusion:Although device porosity is the main parameter influencing flow reduction, other parameters such as device design and local flow conditions may influence the level of flow reduction within intracranial aneurysms.ZusammenfassungHintergrund und Ziel:Die zwei wichtigsten Faktoren für die Entwicklung intrazerebraler Aneurysmen, nämlich Wachstum und Ruptur, hängen vom intraaneurysmatischen Blutfluss ab. Eine Verminderung des intraaneurysmatischen Blutflusses durch minimalinvasive Techniken wird als attraktive Behandlungsmethode erachtet. Eine solche Modifikation des Blutflusses kann durch das Einbringen eines Stents oder „flow diverter“ allein erzielt werden. In der vorliegenden Arbeit untersuchten die Autoren den Effekt der Porosität verschiedener handelsüblicher und innovativer „flow diverters“ an Modellen intrakranieller Aneurysmen.Material und Methodik:Sowohl einzelne oder Stent-in-Stent-Kombinationen des Neuroform II (NF) als auch einzelne oder Stent-in-Stent-Kombinationen von neuen innovativen, niedrigporösen intrakraniellen Stents (D1, D2, D1 + D2) wurden in Modellen intrakranieller Aneurysmen mit Eigenschaften von „shear-driven“ und „inertia-driven“ Fluss platziert. Flächen mit Geschwindigkeitsvektoren in der mittleren Ebene des Aneurysmas parallel zur Achse des Gefäßes wurden mit Hilfe der „particle image velocimetry“ (PIV) ermittelt. Eigenschaften von Fluss und Verwirbelungen, Geschwindigkeit und Ausmaß von Verwirbelungen wurden gemessen und mit Messwerten des gleichen Modells ohne „flow diverter“ verglichen.Ergebnisse:Ohne „flow diverter“ konnte eine beständige Rotation in beiden – „shear-driven“ und „inertia-driven“ – Flussmodellen beobachtet werden. Die Auswirkungen nach Platzierung eines niedrigporösen Modells wie D1 oder D2 riefen eine komplette Änderung der Flusseigenschaften und eine massive Verringerung der Geschwindigkeit und des Ausmaßes von Verwirbelungen hervor, wohingegen die Platzierung klinisch angewendeter hochporöser Modelle geringere Auswirkungen auf die Kavität des Aneurysmas hatte. Erwartungsgemäß haben die Ergebnisse gezeigt: Je kleiner die Porosität ist, desto größer sind die Auswirkungen auf Blutflussgeschwindigkeit und Verwirbelungen im Aneurysma. Die Kombination mit der geringsten Porosität (D1 und D2) erzielte eine durchschnittliche Reduktion der Flussparameter um 80% bzw. 88% bei konstanten und pulsatilen Flüssen. Die Verminderung von mittlerer Geschwindigkeit und von Verwirbelungen war beim „shear-driven“ Fluss deutlich signifikanter als beim „inertia-driven“ Fluss.Schlussfolgerung:Obwohl die Porosität der wichtigste Parameter zur Senkung des Flusses ist, können andere Parameter wie das Design des jeweiligen Modells oder lokale Flusseigenschaften die Wirksamkeit der Flussreduktion in intrakraniellen Aneurysmen beeinflussen.

Penumbra System: A Novel Mechanical Thrombectomy Device for Large-Vessel Occlusions in Acute Stroke

BACKGROUND AND PURPOSE: Large IC artery occlusion is often resistant to recanalization. We present our initial experience with the PS. MATERIALS AND METHODS: Presenting with a severe acute ischemic stroke, the first 27 consecutive patients were considered for thromboaspiration therapy and retrospective data base analysis. All patients received standard thrombectomy treatment as monotherapy or in combination with thrombolysis or IC stent placement. The primary end point was revascularization of the target vessel to grade 2 or 3 on the TICI scale. Secondary end points were improvement of >4 points on the NIHSS score at discharge and favorable outcome, and improvement in overall mortality at 3 months and in sICH- and procedure-related adverse events. RESULTS: At baseline, the mean age was 66 ± 14 years and the mean NIHSS score was 14 ± 7. The anterior circulation was affected in 23 patients, and there were 4 basilar artery occlusions. Intracranial stent placement was performed in 4 patients. A recanalization to TICI 2 or 3 was achieved in 25 patients (93%). None of the patients developed sICH. At hospital discharge, 15 patients (56%) had an NIHSS improvement of >4 and 13 patients (48%) had an mRS score of <2 at 3 months. There was a significant correlation between complete vessel recanalization and favorable outcome. The all-cause mortality at 3 months was 11%. CONCLUSIONS: The PS showed a high potential for recanalization of acute thromboembolic occlusions of the large cerebral arteries. Complete recanalization was strongly correlated with good clinical outcome.