Embolization of middle cerebral artery aneurysms: ready for prime time?
Giuseppe Lanzino and Waleed Brinjikji
Caleb B. Leake, Waleed Brinjikji, David F. Kallmes and Harry J. Cloft
Evidence of better outcomes in patients with aneurysmal subarachnoid hemorrhage treated at higher-volume centers might be expected to result in more of these patients being referred to such centers. The authors evaluated the US National Inpatient Sample for the years 2001 to 2008 for trends in patient admissions for the treatment of ruptured aneurysms at high- and low-volume centers.
The authors determined the number of ruptured aneurysms treated with clipping or coiling annually at low-volume (≤ 20 patients/year) and high-volume (> 20 patients/year) centers and also counted the number of high- and low-volume centers performing each treatment. Hospitalizations for clipping or coiling ruptured aneurysms were identified by cross-matching International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes for the diagnosis of a ruptured aneurysm (ICD-9-CM 430) with procedure codes for clipping (ICD-9-CM 39.51) or coiling (ICD-9-CM 39.52, 39.79, or 39.72) cerebral aneurysms.
In 2001, 31% (435 of 1392) of the patients who underwent clipping and 0% (0 of 122 patients) of those who underwent coiling did so at high-volume centers, whereas in 2008 these numbers increased to 62% (627 of 1016) and 68% (917 of 1351) of patients, respectively. For clipping procedures, the number of low-volume centers significantly declined from 177 in 2001 to 85 in 2008, whereas the number of high-volume centers remained constant at 13–15. For coiling procedures, the number of low-volume centers decreased from 62 in 2001 to 54 in 2008, whereas the number of high-volume centers substantially increased from 0 in 2001 to 16 in 2005 and remained constant thereafter.
The treatment of ruptured cerebral aneurysms increasingly occurs at high-volume centers in the US. This trend is favorable given that better outcomes are associated with the treatment of these lesions at high-volume centers.
Waleed Brinjikji, Ravi K. Lingineni, Chris N. Gu, Giuseppe Lanzino, Harry J. Cloft, Lauren Ulsh, Kristen Koeller and David F. Kallmes
Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages. Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling. To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, the authors studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling.
All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed.
In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61–1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31–1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46–1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21–0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33–1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60–1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23–1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46–1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers.
The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors' institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking.
Waleed Brinjikji, John Huston III, Alejandro A. Rabinstein, Gyeong-Moon Kim, Amir Lerman and Giuseppe Lanzino
Carotid artery stenosis is a well-established risk factor of ischemic stroke, contributing to up to 10%-20% of strokes or transient ischemic attacks. Many clinical trials over the last 20 years have used measurements of carotid artery stenosis as a means to risk stratify patients. However, with improvements in vascular imaging techniques such as CT angiography and MR angiography, ultrasonography, and PET/CT, it is now possible to risk stratify patients, not just on the degree of carotid artery stenosis but also on how vulnerable the plaque is to rupture, resulting in ischemic stroke. These imaging techniques are ushering in an emerging paradigm shift that allows for risk stratifications based on the presence of imaging features such as intraplaque hemorrhage (IPH), plaque ulceration, plaque neovascularity, fibrous cap thickness, and presence of a lipid-rich necrotic core (LRNC). It is important for the neurosurgeon to be aware of these new imaging techniques that allow for improved patient risk stratification and outcomes. For example, a patient with a low-grade stenosis but an ulcerated plaque may benefit more from a revascularization procedure than a patient with a stable 70% asymptomatic stenosis with a thick fibrous cap.
This review summarizes the current state-of-the-art advances in carotid plaque imaging. Currently, MRI is the gold standard in carotid plaque imaging, with its high resolution and high sensitivity for identifying IPH, ulceration, LRNC, and inflammation. However, MRI is limited due to time constraints. CT also allows for high-resolution imaging and can accurately detect ulceration and calcification, but cannot reliably differentiate LRNC from IPH. PET/CT is an effective technique to identify active inflammation within the plaque, but it does not allow for assessment of anatomy, ulceration, IPH, or LRNC. Ultrasonography, with the aid of contrast enhancement, is a cost-effective technique to assess plaque morphology and characteristics, but it is limited in sensitivity and specificity for detecting LRNC, plaque hemorrhage, and ulceration compared with MRI.
Also summarized is how these advanced imaging techniques are being used in clinical practice to risk stratify patients with low- and high-grade carotid artery stenosis. For example, identification of IPH on MRI in patients with low-grade carotid artery stenosis is a risk factor for failure of medical therapy, and studies have shown that such patients may fair better with carotid endarterectomy (CEA). MR plaque imaging has also been found to be useful in identifying revascularization candidates who would be better candidates for CEA than carotid artery stenting (CAS), as high intraplaque signal on time of flight imaging is associated with vulnerable plaque and increased rates of adverse events in patients undergoing CAS but not CEA.
Waleed Brinjikji, David F. Kallmes, Harry J. Cloft and Giuseppe Lanzino
The association between age and outcomes following aneurysm treatment with flow diverters such as the Pipeline Embolization Device (PED) have not been well established. Using the International Retrospective Study of the Pipeline Embolization Device (IntrePED) registry, the authors assessed the age-related clinical outcomes of patients undergoing aneurysm embolization with the PED.
Patients with unruptured aneurysms in the IntrePED registry were divided into 4 age groups: ≤ 50, 51–60, 61–70, and > 70 years old. The rates of the following postoperative complications were compared between age groups using chi-square tests: spontaneous rupture, intracranial hemorrhage (ICH), ischemic stroke, parent artery stenosis, cranial neuropathy, neurological morbidity, neurological mortality, combined neurological morbidity and mortality, and all-cause mortality. The association between age and these complications was tested in a multivariate logistic regression analysis adjusted for sex, number of PEDs, and aneurysm size, location, and type.
Seven hundred eleven patients with 820 unruptured aneurysms were included in this study. Univariate analysis demonstrated no significant difference in ICH rates across age groups (lowest 1.0% for patients ≤ 50 years old and highest 5.0% for patients > 70 years old, p = 0.097). There was no difference in ischemic stroke rates (lowest 3.6% for patients ≤ 50 years old and highest 6.0% for patients 50–60 years old, p = 0.73). Age > 70 years old was associated with higher rates of neurological mortality; patients > 70 years old had neurological mortality rates of 7.4% compared with 3.3% for patients 61–70 years old, 2.7% for patients 51–60 years old, and 0.5% for patients ≤ 50 years old (p = 0.006). On multivariate logistic regression analysis, increasing age was associated with higher odds of combined neurological morbidity and mortality (odds ratio 1.02, 95% confidence interval 1.00–1.05; p = 0.03).
Increasing age is associated with higher neurological morbidity and mortality after Pipeline embolization of intracranial aneurysms. However, the overall complication rates of PED treatment in this group of highly selected elderly patients (> 70 years) were acceptably low, suggesting that age alone should not be considered an exclusion criterion when considering treatment of intracranial aneurysms with the PED.
Stephen P. Lownie and David M. Pelz
Waleed Brinjikji, Mariangela Piano, Shanna Fang, Guglielmo Pero, David F. Kallmes, Luca Quilici, Luca Valvassori, Emilio Lozupone, Harry J. Cloft, Edoardo Boccardi and Giuseppe Lanzino
Flow-diversion treatment has been shown to be associated with high rates of angiographic obliteration; however, the treatment is relatively contraindicated in the acute phase following subarachnoid hemorrhage (SAH) as these patients require periprocedural dual antiplatelet therapy. Acute coiling followed by flow diversion has emerged as an intriguing and feasible treatment option for ruptured complex and giant aneurysms. In this study the authors report outcomes and complications of patients with ruptured aneurysms undergoing coiling in the acute phase followed by planned delayed flow diversion.
This case series includes patients from 2 institutions. All patients underwent standard endovascular coiling in the acute phase after SAH with the intention and plan to proceed with flow diversion at a later date. Outcomes studied included angiographic occlusion, procedure-related complications, and long-term clinical outcome as measured using the modified Rankin Scale.
A total of 31 patients underwent coiling in the acute phase with the intention to undergo flow diversion at a later date. The mean aneurysm size was 15.8 ± 7.9 mm. Of the 31 patients undergoing coiling, 4 patients could not undergo further flow-diverter therapy: 3 patients (9.7%) died of complications of subarachnoid hemorrhage and 1 patient had permanent morbidity as a result of perioperative ischemic stroke (3.1%). Twenty-seven patients underwent staged placement of flow diverters after adequate recovery. The median time to treatment was 16 weeks. There was one case of aneurysm rebleeding following coil treatment. There were no cases of permanent morbidity or mortality resulting from flow-diverter treatment. Twenty-four patients underwent imaging follow-up; 18 of these patients had aneurysms that were completely or nearly completely occluded (58.1% on an intent-to-treat basis). At last follow-up (mean 18.3 months), 25 patients had mRS scores ≤ 2 (80.6% on an intent-to-treat basis).
Staged treatment of ruptured complex and giant intracranial aneurysms with coiling in the acute phase and flow-diverter treatment following recovery from SAH is both safe and effective. In this series, no cases of rebleeding occurred during the interval between coiling and flow diversion. This strategy should be considered as a valid option in patients presenting with these challenging ruptured aneurysms.
Tibor Becske, Matthew B. Potts, Maksim Shapiro, David F. Kallmes, Waleed Brinjikji, Isil Saatci, Cameron G. McDougall, István Szikora, Giuseppe Lanzino, Christopher J. Moran, Henry H. Woo, Demetrius K. Lopes, Aaron L. Berez, Daniel J. Cher, Adnan H. Siddiqui, Elad I. Levy, Felipe C. Albuquerque, David J. Fiorella, Zsolt Berentei, Miklós Marosföi, Saruhan H. Cekirge and Peter K. Nelson
The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial.
The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data.
At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0–1 were demonstrated in 80 subjects.
Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth.
Clinical trial registration no.: NCT00777088 (clinicaltrials.gov)
David F. Kallmes, Waleed Brinjikji, Saruhan Cekirge, David Fiorella, Ricardo A. Hanel, Pascal Jabbour, Demetrius Lopes, Pedro Lylyk, Cameron G. McDougall and Adnan Siddiqui
The authors performed a pooled analysis of 3 studies—IntrePED (International Retrospective Study of the Pipeline Embolization Device), PUFS (Pipeline for Uncoilable or Failed Aneurysms Study), and ASPIRe (Aneurysm Study of Pipeline in an Observational Registry)—in order to assess angiographic outcomes and clinical safety of the Pipeline embolization device (PED).
IntrePED was a retrospective study, while PUFS and ASPIRe were prospective studies. For each patient included in these studies, the authors collected baseline demographic data, aneurysm characteristics, and procedural details. The primary outcomes for this combined analysis were clinical outcomes, including neurological morbidity and mortality and major ipsilateral intracranial hemorrhage and ischemic stroke. The secondary outcomes were angiographic occlusion rates, which were available for ASPIRe and PUFS only.
A total of 1092 patients with 1221 aneurysms were included across the 3 studies. The mean aneurysm size was 12.0 ± 7.8 mm and the mean neck size was 6.6 ± 4.8 mm. The major ipsilateral ischemic stroke rate was 3.7% (40/1091). The major ipsilateral intracranial hemorrhage rate was 2.0% (22/1091). The major neurological morbidity rate was 5.7% (62/1091). The neurological mortality rate was 3.3% (36/1091). The combined major morbidity and neurological mortality rate was 7.1% (78/1091). The complete occlusion rates were 75.0% at 180 days (111/148) and 85.5% at 1 year (94/110). The overall aneurysm retreatment rate was 3.0% (33/1091) at a mean follow-up time of 10.2 ± 10.8 months.
Endovascular treatment of intracranial aneurysms with the PED is safe and effective. Angiographic occlusion rates progressed with follow-up. Rates of stroke, hemorrhage, morbidity and mortality, and retreatment were low, especially given the fact that the aneurysms treated were generally large and wide necked.