Guylaine Gevry

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 10 845 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.

Role of the Endothelial Lining in Recurrences After Coil Embolization: Prevention of Recanalization by Endothelial Denudation

Background and Purpose— Endovascular treatment can improve the outcome of patients treated for ruptured intracranial aneurysms as compared with surgical clipping, but angiographic recurrences are frequent. Endothelial denudation before coil embolization may prevent recanalization and improve results of endovascular treatment. Methods— We compared angiographic and pathological results 3 months after coil occlusion of paired canine arteries (n=16), with or without previous denudation of the endothelial lining using an endovascular device. The technique was then used to denude the neck of carotid venous pouch bifurcation aneurysms before coil embolization in 8 dogs, and the angiographic evolution at 12 weeks was compared with 7 control aneurysms treated by coiling only. Qualitative scoring systems were used to compare angiographic results with time and neointimal coverage at the neck of aneurysm after necropsy. The evolution of angiographic scores was analyzed using Wilcoxon signed rank tests whereas angiographic and neointimal scores of the 2 groups were compared using the Mann–Whitney test. Results— All arteries embolized with platinum coils recanalized, whereas most arteries (12/16 or 75%) denuded before coil embolization remained occluded at 3 and 12 weeks (P < 0.001). Aneurysms treated with coils without previous denudation tended to recur, with angiographic scores significantly worse at 12 weeks as compared with T0 (P = 0.015). Median angiographic and neointimal scores were significantly better at 12 weeks with endothelial denudation (P = 0.011 and 0.026, respectively). Conclusion— Endothelial denudation can prevent recanalization after coil embolization.

Endovascular Treatment of Intracranial Aneurysms With Radioactive Coils Initial Clinical Experience

Background and Purpose— Endovascular treatment of intracranial aneurysms is safe and effective but is associated with angiographic recurrences. Beta radiation prevents recanalization after coil embolization in experimental models. We wanted to assess the feasibility of using radioactive coil embolization to improve long-term results of endovascular treatment. Methods— Platinum coils were ion-implanted with 0.13 to 0.26 &mgr;Ci/cm of 32P. Forty-one patients aged 34 to 84 years with 44 aneurysms with a high propensity for recurrences were included. Radioactive coils were introduced into aneurysms to reach a target volumetric activity of 0.018 &mgr;Ci/mm3. Nonradioactive coils were also used to ensure the same safety and the same angiographic results as the standard procedure. Angiographic results, procedure-related complications, and neurological events during follow-up were recorded. Angiographic follow-up data are available in 36 lesions 6 months after treatment. Results— Forty of 44 aneurysms (91%) could be treated with radioactive coils. Target activities could be reached in 88% of lesions that could actually be coiled (35/40). Total activities ranged from 1.72 to 80.9 &mgr;Ci, for a mean of 20.13±20.80 &mgr;Ci. Procedure-related complications occurred in 7% of patients. Initial angiographic results were satisfactory (complete occlusions or residual necks) in 75% of lesions. Angiographic recurrences occurred in 11 (31%) of patients followed, within the expected range for standard coils. There was no complication from beta radiation during a mean follow-up period of 10 months. Conclusions— Radioactive coil embolization is feasible; target volumetric activities can be reached in most aneurysms considered for endovascular treatment.

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.

Flow diverters failing to occlude experimental bifurcation or curved sidewall aneurysms: an in vivo study in canines

OBJECT Flow diverters (FDs) are increasingly used to treat complex intracranial aneurysms, but preclinical studies that could guide clinical applications are lacking. The authors designed a modular aneurysm model in canines to address this problem. METHODS Three variants of one modular aneurysm model were constructed in 21 animals. Sidewall (n=5), curved sidewall (n=5), and end-wall bifurcation (n=7) aneurysms were treated with prototype 36-wire FDs. Four more end-wall bifurcation aneurysms were treated with prototype 48-wire lower-porosity FDs. Angiographic results postimplantation and at 3 months were scored with an ordinal scale. Animals were euthanized at 3 (n=17) or 6 (n=3) months, and the FD covering the aneurysm ostium was photographed to analyze metallic porosity and amount of neointima formation. RESULTS Straight sidewall aneurysms were better occluded than curved sidewall and end-wall bifurcation aneurysms at the 3-month angiography follow-up (p=0.010). Flow diverters failed to occlude curved sidewall aneurysms (n=0/5) and all but one (n=1/7) end-wall bifurcation aneurysm. Angiographic results were no better (n=0/4) using a 48-wire FD (p=0.788). Branches jailed by the FD (n=16) remained patent in all cases. Metallic porosity was decreased (p=0.014) and neointimal closure of the aneurysm ostium was more complete (p=0.040) in sidewall aneurysms than in curved or bifurcation variants of the model. CONCLUSIONS Flow diverters may succeed in treating straight sidewall aneurysms, but the same device repeatedly fails to occlude curved sidewall and end-wall bifurcation aneurysms. In vivo studies can be designed to test basic principles that, once validated, may serve to guide clinical use of new devices.

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.

Beta Radiation and Inhibition of Recanalization After Coil Embolization of Canine Arteries and Experimental Aneurysms How Should Radiation Be Delivered

Background and Purpose— Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32P per centimeter of coil or per volume, and spatial distribution of coils on recanalization. Methods— We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 &mgr;Ci/cm) of 32P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination. Results— All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks. Conclusions— The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

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.

Thrombosis Heralding Aneurysmal Rupture: An Exploration of Potential Mechanisms in a Novel Giant Swine Aneurysm Model

BACKGROUND AND PURPOSE: The relationship between aneurysm dimensions, flow, thrombosis, and rupture remains poorly understood. We attempted to clarify this relationship by exploring various swine aneurysm models. MATERIALS AND METHODS: Bilateral carotid aneurysms were constructed according to 3 protocols in 24 animals: small aneurysms with wide necks (group 1; n = 6 animals); small aneurysms with small necks (group 2; n = 4 animals), and giant aneurysms with large necks (group 3; n = 14 animals). Group 3 included 3 subgroups, related to testing the model in various experimental conditions: The neck was clipped in 3 animals; venous pouches lacked an endothelial lining in 4 animals; and 7 were control animals. Animals were followed until rupture, or for 1–4 weeks. Angiography was performed postoperatively and before euthanasia. We studied lesion pathology, paying attention to thrombosis, recanalization, wall composition, and perianeurysmal hemorrhage. RESULTS: Groups differed significantly in aneurysm dimensions and aspect ratio (P = .002). Ruptures occurred more frequently in animals with untreated giant aneurysms (7/7) than in animals with small wide-neck (0/6) or small-neck (2/4) aneurysms (P = .002). Ruptures occurred only in animals with thrombosed aneurysms. Lesions lacking an endothelial lining and 5 of 6 clipped venous pouches thrombosed but did not rupture. One giant lesion ruptured despite complete clipping. The wall was deficient in α-actin and was infiltrated with inflammatory cells and erythrocytes in all thrombosed cases, ruptured or not. Ruptures were associated with recanalizing channels in 9 of 10 cases. CONCLUSIONS: Thrombosis, inflammation, and recanalization may precipitate aneurysmal ruptures in a swine model