T.E. Darsaut

Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011

Background and purpose Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. Methods A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990–April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I2, and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. Results 60 studies with 9845 patients harbouring 10u2005845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I2=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I2=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. Conclusions In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

A trial on unruptured intracranial aneurysms (the TEAM trial): results, lessons from a failure and the necessity for clinical care trials

The trial on endovascular management of unruptured intracranial aneurysms (TEAM), a prospective randomized trial comparing coiling and conservative management, initiated in September 2006, was stopped in June 2009 because of poor recruitment (80 patients). Aspects of the trial design that may have contributed to this failure are reviewed in the hope of identifying better ways to successfully complete this special type of pragmatic trial which seeks to test two strategies that are in routine clinical use. Cultural, conceptual and bureaucratic hurdles and difficulties obstruct all trials. These obstacles are however particularly misplaced when the trial aims to identify what a good medical practice should be. A clean separation between research and practice, with diverging ethical and scientific requirements, has been enforced for decades, but it cannot work when care needs to be provided in the presence of pervasive uncertainty. Hence valid and robust scientific methods need to be legitimately re-integrated into clinical practice when reliable knowledge is in want.A special status should be reserved for what we would call clinical care trials, if we are to practice in a transparent and prospective fashion a medicine that leads to demonstrably better patient outcomes.

The Varying Porosity of Braided Self-Expanding Stents and Flow Diverters: An Experimental Study

BACKGROUND AND PURPOSE: Braided self-expandable stents and flow diverters of uniform construction may develop zones of heterogeneous porosity in vivo. Unwanted stenoses may also occur at the extremities of the device. We studied these phenomena in dedicated benchtop experiments. MATERIALS AND METHODS: Five braided devices of decreasing porosity were studied. To simulate discrepancies in diameters between the landing zones of the parent vessel and the aneurysm neck area, device extremities were inserted into silicone tubes of various diameters (2–3 mm), leaving the midportion free to react to experimental manipulations, which included axial approximation of the tubes (0–7 mm), and curvature (0–135°), with or without axial compression (0–2 mm). The length of the landing zone was sequentially decreased to study terminal device stenosis. RESULTS: All devices adopted a conformation characterized by 3 different zones: bilateral landing zones, a middle compaction zone, and 2 transition zones. It is possible, during deployment, to compact stents and FDs to decrease porosity, but a limiting factor was the transition zone, which remained relatively unchanged and of higher porosity than the expansion zone. Length of the transition zone increased when devices were constrained in smaller tubes. Heterogeneities in porosity with compaction and curvatures were predictable and followed simple geometric rules. Extremity stenoses occurred increasingly with decreasing length of the landing zone. CONCLUSIONS: Braided self-expandable devices show predictable changes in porosity according to device size, vessel diameter, and curvature. Adequate landing zones are required to prevent terminal device stenosis.

Flow Diverters Can Occlude Aneurysms and Preserve Arterial Branches: A New Experimental Model

BACKGROUND AND PURPOSE: FDs are new intracranial stents designed to occlude aneurysms while preserving flow to jailed arterial branches. We tested this fundamental principle in a new aneurysm model. MATERIALS AND METHODS: Canine lateral wall aneurysms, featuring a branch located immediately opposite the aneurysm, were created in 16 animals to study the effects on aneurysm or branch occlusion using single HP stents (n = 4), 2 overlapping HP stents (n = 4), or an FD (n = 8). Two other animals, in which an efferent arterial branch was anastomosed to the aneurysm fundus, were also treated with FDs. Angiographic results after deployment, at 2 weeks, and at 3 months were scored using an ordinal scale. The metal porosity of the FSS and the amount of FSS neointima formation was determined by postmortem photography. RESULTS: FDs led to better angiographic occlusion scores compared with HP stents (P = .026). FDs were significantly more likely to occlude the aneurysm than the branch (P = .01). When the branch was switched to originate from the aneurysm fundus, the FDs became ineffective (0/2). Neointimal closure of the aneurysm ostium was significantly better with FDs than with single or double HP stents (P = .039). Angiographic occlusion correlated with metallic porosity and neointimal tissue coverage (Spearman ρ = −0.81; P = .001). CONCLUSIONS: In this study, flow diverters occluded lateral wall aneurysms more readily than branches. Metal device porosity strongly influenced the occlusion rate.

Mechanisms of Occlusion and Recanalization in Canine Carotid Bifurcation Aneurysms Embolized with Platinum Coils: An Alternative Concept

BACKGROUND AND PURPOSE: Endovascular treatment of aneurysms may result in complete or incomplete occlusions or may be followed by recurrences. The goal of the present study was to better define pathologic features associated with so-called healing or recurrences after coiling and to propose an alternative concept to the currently accepted view. MATERIALS AND METHODS: Experimental canine venous pouch aneurysms were created by using a T-type (group A, N = 29) or a Y-type constructed bifurcation (group B, N = 37) between the carotid arteries. Coil embolization was performed 2 weeks later; and angiography, immediately after and at 12 weeks. Angiographic results, neointima formation at the neck, endothelialization, and organization of thrombus were compared between groups by using qualitative scores and immunohistochemistry. RESULTS: Angiographic results at 3 months were significantly better in group A than in group B (P = .001). Macroscopic neointimal scores were also better (P = .012). Only 10/32 aneurysms with satisfactory results at angiography were completely sealed by neointima formation. Animals with residual or recurrent aneurysms had significantly worse neointimal scores than those with completely occluded ones (P = .0003). On histologic sections, the neointima was constantly present in “healed” and in recurrent aneurysms. This neointima was a multicellular layer of α-actin+ cells in a collagenous matrix, covered with a single layer of nitric oxide synthetase (NOS+) endothelial cells, whether it completely occluded the neck of the aneurysm or dived into the recurring or residual space between the aneurysm wall and the coil mass embedded in organizing thrombus. CONCLUSION: Complete angiographic occlusions at 3 months can be associated with incomplete neointimal closure of the neck at pathology. Thrombus organization, endothelialization, and neointima formation can occur concurrently with recurrences.

Outcomes of Endovascular Treatments of Aneurysms: Observer Variability and Implications for Interpreting Case Series and Planning Randomized Trials

BACKGROUND AND PURPOSE: Angiographic results are commonly used as a surrogate marker of success of coiling of intracranial aneurysms. Inter- and intraobserver agreement in judging angiographic results remain poorly characterized. Our goal was to offer such an evaluation of a grading scale commonly used to evaluate results of endovascular treatment of aneurysms. MATERIALS AND METHODS: A portfolio of 90 angiographic images from 45 patients selected from the core lab data base of a randomized trial was sent to 12 observers on 2 occasions more than 3 months apart. The variability of a 3-value grading scale used to score angiographic results and of a final judgment regarding the presence of a recurrence was studied using κ statistics. RESULTS: Ten participants responded once and 6 responded twice. Agreement was poor to moderate (κ = 0.28–0.5) for senior and junior observers judging angiographic results immediately or 12–18 months after treatment. Agreement reached a reassuring “substantial” (κ = 0.62) level, with a dichotomous presence-absence of a major recurrence, and intraobserver agreement was better in experienced core lab assessors. CONCLUSIONS: There is an important variability in the assessment of angiographic outcomes of endovascular treatments, rendering comparisons between publications risky, if not invalid. A simple dichotomous judgment can be used as a surrogate outcome in randomized trials designed to assess the value of new endovascular devices.

Liquid embolization material reduces the delivered radiation dose: clinical myth or reality?

BACKGROUND AND PURPOSE: To be radiopaque, BAVM embolization products must contain high-atomic-number materials, which may also attenuate photon beams delivered with radiosurgery. This “shielding effect” has been invoked to explain why radiation therapy may be less effective for previously embolized BAVMs. To evaluate the impact of embolization material on radiation dose, we measured and compared the dose delivered to the center of an AVM model, before and following embolization with various materials in a LINAC. MATERIALS AND METHODS: Two in vitro AVM models were constructed by drilling interconnected tubular perforations in plastic water phantoms to simulate nidal vessels. Phantoms were designed to allow the positioning of a radiation detector at their center. One model was embolized with Onyx 18 and a second model, with a combination of Indermil, Lipiodol, tungsten powder, and Onyx 18. The radiation delivered was compared between embolized and nonembolized controls following irradiation with a standard 250-cGy dose. RESULTS: The mean dose of radiation delivered to the model embolized with Onyx alone was 244 ± 5 cGy before and 246 ± 5 cGy following embolization. The mean dose of radiation delivered to the model embolized with various agents was 242 ± 5 cGy before, and 254 ± 5 cGy after embolization. CONCLUSIONS: Embolic material did not reduce the radiation dose delivered by a LINAC to the center of our experimental BAVM models. The shielding effect may be compensated by scattered and reflected radiation.

Testing Flow Diverters in Giant Fusiform Aneurysms: A New Experimental Model Can Show Leaks Responsible for Failures

BACKGROUND AND PURPOSE: FDs are the latest, most promising tool to treat giant and complex aneurysms. Currently available experimental aneurysm models do not reproduce the potential clinical difficulties of treating these lesions with FDs. MATERIALS AND METHODS: Six large or giant canine fusiform aneurysms were created on the distal carotid arteries of 4 animals. Four of the aneurysms had multiple arterial branches originating from the aneurysm; 2 other aneurysms had all branches clipped at the time of aneurysm construction. Aneurysms were treated with multiple telescoping prototype flow-diverting stents (total of 15 FDs). Angiography was carried out before and immediately after implantation, at 2 weeks, and immediately before sacrifice at 12 weeks. Macroscopic photography of specimens was performed, followed by biopsies of selected regions of the tissue formed on the surface of FDs. RESULTS: Technical or device-related difficulties occurred in 2 of 6 aneurysm treatments. Fusiform aneurysms with branches intact remained widely patent (mean angiographic score, 3), whereas aneurysms with clipped branches had only small residua (mean angiographic score, 1) at 12 weeks. The presence of very small defects in neointima formation on the surface of FDs, or leaks, was sufficient for residual filling of the aneurysms, which served as reservoirs to feed branches. CONCLUSIONS: Experimental canine fusiform carotid aneurysms may reproduce many of the difficulties associated with the treatment of giant aneurysms and could be appropriate for preclinical testing of FD stents.

Stent-Assisted Coiling of Bifurcation Aneurysms May Improve Endovascular Treatment: A Critical Evaluation in an Experimental Model

BACKGROUND AND PURPOSE: Endovascular treatment of wide-neck bifurcation aneurysms often results in incomplete occlusion or aneurysm recurrence. The goals of this study were to compare results of coil embolization with or without the assistance of self-expandable stents and to examine how stents may influence neointima formation. MATERIALS AND METHODS: Wide-neck bifurcation aneurysms were constructed in 24 animals and, after 4–6 weeks, were randomly allocated to 1 of 5 groups: 1) coil embolization using the assistance of 1 braided stent (n = 5); 2) coil embolization using the assistance of 2 braided stents in a Y configuration (n = 5); 3) coil embolization without stent assistance (n = 6); 4) Y-stenting alone (n = 4); and 5) untreated controls (n = 4). Angiographic results were compared at baseline and at 12 weeks, by using an ordinal scale. Neointima formation at the neck at 12 weeks was compared among groups by using a semiquantitative grading scale. Bench studies were performed to assess stent porosities. RESULTS: Initial angiographic results were improved with single stent–assisted coiling compared with simple coiling (P = .013). Angiographic results at 12 weeks were improved with any stent assistance (P = .014). Neointimal closure of the aneurysm neck was similar with or without stent assistance (P = .908), with neointima covering coil loops but rarely stent struts. Y-stent placement alone had no therapeutic effect. Bench studies showed that porosities can be decreased with stent compaction, but a relatively stable porous transition zone was a limiting factor. CONCLUSIONS: Stent-assisted coiling may improve results of embolization by allowing more complete initial coiling, but these high-porosity stents did not provide a scaffold for more complete neointimal closure of aneurysms.

Ruptured aneurysms and the International Subarachnoid Aneurysm Trial (ISAT): What is known and what remains to be questioned

BACKGROUND AND PURPOSEnThe International Subarachnoid Aneurysm Trial (ISAT) was a major study comparing clipping and coiling of ruptured intracranial aneurysms. The trial provided answers that were the subject of multiple letters and editorial comments.nnnMETHODSnWe review the most common critiques that were published in major neurosurgical journals, trying to identify what aspects of ISAT could have been improved, and what questions remain to be studied.nnnRESULTSnFrequent critiques include imprecise selection criteria, lack of requirement for the technical proficiency of surgical participants, lack of angiographic controls of surgically treated patients, and poorly chosen primary endpoints. Other issues that are often raised are the poor recruitment rate which endangered generalization of results, the excessive delays in performing clipping which led to rebleeding episodes, lack of blinding in the assessment of outcomes, and subjective questionnaires. Nonetheless, the design of the study as a pragmatic trial was appropriate, as was the choice of the primary endpoint. The overall trial results could not be verified for all subgroups of interest, and currently many patients who would not have been included in ISAT are treated by coiling, while other patients are treated by clipping despite ISAT results. Hence a new trial, complementary to the original ISAT, may now be indicated.nnnCONCLUSIONnISAT was well-designed and conducted, but many questions remain. They should be addressed by a new trial.