Recent advances in angiographic technique have raised our awareness of the presence of unruptured intracranial aneurysms (UIAs). However, the appropriate management for these lesions remains controversial. To optimize patient outcomes, the physician must weigh aneurysmal rupture risk associated with observation against the complication risks associated with intervention. In the case that treatment is chosen, the two available options are surgical clipping and endovascular coiling. Our paper summarizes the current body of literature in regards to the natural history of UIAs, the evolution of the lesion if it progresses uninterrupted, as well as the safety and efficacy of both treatment options. The risks and benefits of treatment and conservative management need to be evaluated on an individual basis and are greatly effected by both patient-specific and aneurysm-specific factors, which are presented in this paper. Ultimately, this body of data has led to multiple sets of treatment guidelines, which we have summated and presented in this paper.
Despite an abundance of published data, management of patients with unruptured intracranial aneurysms (UIAs) remains controversial. Advances in imaging and more frequent use of CTA and MRA over the last two decades have elucidated the pervasiveness of intracranial aneurysms. Furthermore, these imaging techniques have been refined over the years giving them greater sensitivity and specificity and increasing the number of cerebral aneurysms found incidentally. Ultimately, physicians have realized that UIAs are rather common. Imaging studies have reported frequencies of 0.5% to 2%, while autopsy studies have reported frequencies of 1% to 9% [
The inherent threat of UIAs is rupture and subsequent subarachnoid hemorrhage (SAH). Recent studies of aneurysmal SAH, which accounts for around 80% of nontraumatic SAH, have reported 1-month case mortality rates as high as 30% to 50% [
Universal treatment protocols for patients with UIAs have yet to be established. Intervention by surgical clipping or endovascular coiling constitutes one strategy, while others have opted for conservative management and observation. Chief in this clinical evaluation is balancing the risk of treatment with that of observation. A variety of largely nonrandomized studies have implicated different patient characteristics (age, medical condition, history of SAH, etc.), aneurysm characteristics (size, location, morphology, neck size, etc.) and management factors (surgical team, treating hospital), as being influential in the natural history and outcomes following treatment [
Characterizing the aneurysmal rupture risk of UIAs, known as their natural history, is a task that has proven very difficult over the years. While much has been revealed about UIAs from retrospective review, inconsistencies and methodological flaws in studies regarding UIAs have resulted in a poorly defined natural history. Several reasons explain why this uncertainty exists. Paramount among them is the fact that natural history studies of UIAs only evaluate those patients for whom conservative management was decided. It has therefore been argued that data from these studies do not represent the behavior of all UIAs, only certain types. The current body of published literature has thoroughly evaluated aneurysms on the basis of many different risk factors, which can be roughly divided into patient-specific and aneurysm-specific factors. Table
Key findings related to the natural history data.
Risk factor | Key findings | References |
---|---|---|
Size | (i) Larger UIAs have greater RR | ISUIA investigators 1998 [ |
Enlargement | (i) In most cases, IAs are larger at time of rupture than at initial diagnosis | Yasui et al. 1996 [ |
Previous SAH | (i) Prior history of aneurysmal SAH increases future RR | ISUIA investigators 1998 [ |
Location | (i) Posterior circulation aneurysms are widely considered to be more hazardous | Weir et al. 2002 [ |
Morphology | (i) Multiple lobulations or loculations increases RR | Hademenos et al. 1998 [ |
Patient characteristics | (i) Age, sex and comorbidities will influence aneurysmal RR |
Nahed et al. 2005 [ |
In almost all natural history studies to date, size has been found to be a significant predictor of aneurysm rupture. In general, the notion that large UIAs have a greater rupture risk than small UIAs is widely accepted. However, an exact size threshold above which UIAs impart significantly greater rupture risk has yet to established [
The largest multicenter study of UIAs at the time, the ISUIA (International Study of Unruptured Intracranial Aneurysms), aimed to characterize the natural history of unruptured aneurysms. The retrospective cohort of the ISUIA study found that, in patients without previous history of SAH, UIAs of less than 10 mm in diameter had a rupture rate (RR) of 0.05% per year. It also found that UIAs more than 10 mm in diameter had an RR of less than 1% per year. The authors initially concluded that UIAs were more benign than previously reported [
More recent natural history studies continue to reinforce the importance of size in evaluating rupture risk. A study by Ishibashi et al. classified aneurysms by size, small (<5 mm), medium (5–9.9 mm), large (>10 mm), and giant (>25 mm), and found annual RRs of 0.8%, 1.2%, 7.1%, and 43.1%, respectively [
The growth of UIAs over time is important to the clinician for multiple reasons. For one, it has been hypothesized that an increase in UIA size might be indicative of forthcoming rupture, even in smaller aneurysms. One study by Yasui et al. specifically analyzed 25 cases of SAH caused by rupture of a conservatively managed intracranial aneurysm. The results of this study found that in most cases the diameter at time of rupture was greater than the diameter at initial diagnosis. Furthermore, of these 25 cases, 16 dealt with aneurysms that were <5 mm at initial diagnosis [
Another study, completed in 2008 by Burns et al., evaluated enlargement as a risk factor for aneurysm rupture. The study retrospectively identified 165 patients with 191 UIAs followed with serial MR angiography and discovered that, after a median follow-up period of 47 months, 20 aneurysms (~10%) grew. Frequency of enlargement was 6.9%, 25%, and 83% for aneurysms <8 mm, 8 to 12 mm, and ≥13 mm, respectively [
Among the chief goals of the ISUIA was better understanding the role that previous medical history, particular one with aneurysmal SAH, had on future rupture risk. Consequently, the retrospective component of the ISUIA, stratified its patients into two groups, with group 1 consisting of patients who had no history of SAH and group 2 consisting of patients who had a history of SAH from a different aneurysm. The patients in group 2 with UIAs <10 mm possessed an RR of 0.5% per year, a figure which is ~11 times higher than that for patients in group 1 with aneurysms of the same size [
As the various cerebral blood vessels have different characteristics and experience different hemodynamic conditions, one would expect location of the aneurysm to influence its natural history. Some studies had originally identified aneurysms at the anterior communicating and pericallosal arteries as being at high risk of rupture [
On the other hand, UIAs in the intracavernous ICA have been found to be more benign. This portion of the ICA is seldom located in the subarachnoid space, and thus rupture of these aneurysms rarely causes SAH [
Atypical aneurysm morphology, such as multilobulation and loculations, daughter sac formation, and other unique hemodynamic factors play roles in raising the risk of rupture [
Given that intracranial aneurysms are more commonly found at either bi- or trifurcations or at regions of high impact from flowing blood, the relationship of aneurysm to the surrounding vasculature has been examined [
Novel technology providing three-dimensional angiographic images has facilitated visualization of cerebral vasculature and helped investigators analyze aneurysm morphology. Dhar et al. utilized this technology to evaluate UIAs based on eight parameters, three of which incorporate parent vessel geometry and had not been previously explored (vessel angle, aneurysm (inclination) angle, and (aneurysm-to-vessel) size ratio) [
Patient factors such as age, sex (females are 1.5–3 times more likely to have a ruptured aneurysm), and comorbidities, such as hypertension and cigarette smoking, influence whether an aneurysm will rupture [
The most appropriate treatment option for any UIA is that which provides an optimal balance of procedural safety and long-term efficacy based on patient and aneurysm characteristics. Currently, there are two available options for treating UIAs, microsurgical clipping and endovascular coiling. For each of these treatment modalities, recurrence, retreatment, and percent occlusion data have been gathered to quantify efficacy, while morbidity/mortality and procedural complication rates have been utilized to quantify safety. Although the merits of each treatment are well documented, the superiority of one treatment over the other remains controversial. This section of the paper presents both the current data regarding each treatment and the proposed guidelines set forth to help physicians optimize patient outcomes.
Traditionally, surgical clipping has been viewed as being highly efficacious, but carrying greater risk due to the neurological complications associated with open neurosurgery. Efficacy of this treatment is illustrated by a study performed between 1998 and 2001 that explored the need for cerebral angiography following surgery for saccular aneurysms. Of the 315 surgically clipped UIAs in this study, 287 were completely occluded, a 91% complete occlusion rate [
Another goal of the prospective branch of the ISUIA was to obtain a more comprehensive assessment of the surgical risks of aneurysm clipping. Among the 1917 patients who underwent surgical clipping, the study found a 1-year mortality rate of 2.3% and a 1-year morbidity rate of 12.1%. The study also found that increasing aneurysmal size and patient age as well as location in the posterior circulation (particularly basilar tip and posterior communication artery) are indicators of poor outcome following surgical treatment [
Based on the natural history data presented in the ISUIA, Krisht et al. calculated that (according to size parameters) patients on their service whom had chosen surgical treatment would have had a 10-year cumulative bleeding-related mortality and severe morbidity rate of no less than 7.5% had they chosen conservative management. This figure is significantly greater than the 4.2% combined morbidity and mortality rates that their patient population actually experienced, suggesting that surgical treatment may represent a superior approach to conservative management in patients with life expectancies greater than 10 years [
More recent studies are showing that refinement of microsurgical technique is leading to safer, more efficacious treatment of UIAs. One study followed a series of 450 aneurysms treated with surgical clipping by one neurosurgeon immediately upon completion of neurosurgery training. With 6-month morbidity and mortality rates of 1.06% and 0.27%, respectively, it is clear that, despite an increase in endovascular procedures, given proper mentorship and resources prevailing neurosurgeons can achieve acceptable results when treating UIAs surgically [
As previously mentioned, the expertise and experience of the neurosurgical team and treating hospital will also affect postoperative outcomes. A study at the Cleveland Clinic of 499 aneurysms, treated by 10 neurosurgeons, found that the number of aneurysms clipped by a specific neurosurgeon was a strong predictor of positive outcome, along with patient age and aneurysm size [
Since its conception and implementation about two decades ago [
(a) Preoperative 3D digital subtraction angiogram (DSA) of a left 6.6 mm pericallosal UIA. 54-year-old female patient had prior history of SAH and harbored multiple smaller aneurysms on the right. Endovascular coiling was chosen. (b) Postoperative 3D DSA. Treatment achieved 99% occlusion.
Preoperative DSA of a 4.1 mm × 3.2 mm ACOM aneurysm. This specific UIA was chosen for endovascular treatment due to enlargement and visual field deficits. (b) Postoperative DSA. Endovascular coiling produced near complete occlusion.
In addition to degree of occlusion, the efficacy of treatments for UIAs, especially endovascular coiling, has been measured by recanalization and retreatment rates. These rates quantify the long-term effectiveness of coiling and help surgeons and physicians understand how much treatment is altering the natural history of these lesions. One multicenter study published by Gallas et al. in 2009 analyzed intracranial aneurysms treated within five-year period from 1998 to 2003 and included a mean follow-up time of 55.6 months [
To confirm the notion that endovascular procedures provide a safe alternative for treating UIAs, many studies have investigated the morbidity and mortality rates of patients who underwent endovascular coiling. As part of the prospective branch of the ISUIA, 451 patients were chosen to undergo endovascular coiling. Among these patients, there was a 1-year surgery-related mortality rate of 3.1% and a 1-year morbidity rate of 9.5% [
While endovascular treatment of UIAs is now widely used, certain aneurysmal morphologies and anatomical features, particularly a wide neck, render some aneurysms technically difficult to treat endovascularly. To facilitate endovascular coiling of aneurysms with broad necks, Moret et al. extended a previously utilized temporary balloon-inflation technique to the treatment of UIAs and named it balloon remodeling [
Another adjunctive therapy for wide-neck UIAs is microcatheter-delivered stenting. The hope among neurosurgeons is that stent-assisted coil embolization (SAC) may improve long-term durability and effectiveness by minimizing herniation and increasing packing density [
3D DSA of a giant, left, petrous ICA aneurysm. Stent-assisted coiling was performed on this patient.
For many years, microsurgical clipping of aneurysms was considered the “gold standard” of treatment for UIAs. However, emerging attitudes favoring noninvasive procedures have coincided with a steep increase in gross number and variety of aneurysms treated endovascularly [
In order to settle this controversy, many studies have directly compared endovascular coiling to surgical clipping. A multicenter retrospective cohort study of over 2500 UIAs treated with either coiling or clipping between 1998 and 2000 revealed significantly lower morbidity (6.6% versus 13.2%) and mortality (0.9% versus 2.5%) in those patients treated endovascularly [
While numerous RCTs have investigated the treatment safety and efficacy of RIAs [
The clinical evaluation of UIA patients also must consider the economic burdens of each treatment. This reality is particularly valid when the treatment rationale is unclear, as is the case in UIA treatment. Investigators in Europe initially reported that there was no significant difference between cost of endovascular coiling and surgical clipping [
The endovascular approach to UIA treatment, having only been FDA approved since the early 1990s, remains a relatively new option. As such, there is still a great deal of research and innovation occurring in the field, which frequently leads to new technologies. The hope with these advances is that neurosurgeons will be able to treat a wider spectrum of intracranial aneurysms with greater safety and efficacy, lowering incomplete occlusion and recanalization rates while maintaining acceptable levels of morbidity and mortality.
While primarily used in the treatment of arteriovenous malformations (AVMs), liquid embolic systems such as Onyx HD-500 (EV3, Irvine, CA, USA) are becoming an increasingly popular option in the treatment of wide-necked intracranial aneurysms. Compared with standard platinum coil embolization, liquid embolic systems are posited to provide greater neck and parent vessel reconstruction while also inducing greater neoendothelization of the aneurysm neck. One retrospective study of 84 wide-necked intracranial aneurysms treated with Onyx HD-500 (74 of which were unruptured) found there to be an overall complete occlusion rate of 65.5% immediately following the procedure. Furthermore, 68.2% of the incompletely occluded aneurysms progressed to complete occlusion by 6 months, and, by 18 months, 90.3% of all aneurysms achieved complete occlusion. Procedural morbidity and mortality rates in this study were 7.2% and 2.9%, respectively [
Another, more recently approved, endovascular approach is parent vessel reconstruction using a pipeline (EV3, Irvine, CA, USA) embolization device (PED). Similar to the microstent, the PED is a self-expanding, microcatheter-delivered, cylindrical mesh device. However, its 30–35% metal surface area coverage (compared to the 6–9% coverage of self-expanding microstents) allows it to function as a stand-alone reconstruction device, diverting blood flow away from the aneurysm [
In 2000 the American Heart Association’s Stroke Council published a list of recommendations to provide the physician with a framework for making appropriate treatment decisions. In these recommendations, the council emphasizes patient age in the clinical evaluation, noting that the higher treatment risks and shorter life expectancies of older people favor observation, especially in the case of small, asymptomatic UIAs. For example, conservative management might be suggested for an older patient with a UIA ≥10 mm, while treatment might be recommended for young patients with UIAs between 5 mm and 9 mm. Furthermore, the council recommends treatment for all patients with prior history of aneurysmal SAH as well as all symptomatic, intradural UIAs and UIAs ≥10 mm, unless age or medical condition limit treatment benefits. Additionally, special consideration should be given to aneurysms with unusual morphology such as multilobulations as well patients with a family history of aneurysms or SAH [
However, the wealth of recently published data on UIA treatment has led many physicians to implement their own protocols based on the studies they find most credible among the literature. Many emphasize aneurysm size in their clinical evaluation, but these decisions are complex and require consideration of many other factors as well. The first decision is whether to treat. At Columbia University as of 2007, the neurosurgical team reported that their interpretation of the literature and the experience of their microsurgeons and endovascular surgeons have led them to believe that all symptomatic aneurysms, aneurysms from 5–10 mm in patients under 60 years old, and aneurysms >10 mm in patient under 70 years old should be strongly considered for treatment [
Comparatively, the management summary submitted by Robert Brown, a Professor of Neurology at the Mayo Clinic College of Medicine, cites different size thresholds, a more aggressive attitude towards intervention and an emphasis on patient perspective [
Further, while some surgeons recommend microsurgical clipping as the first treatment choice because of its proven long-term efficacy [
Treatment recommendations.
Source | Recommendations |
---|---|
American Heart Association’s Stroke Council | (1) Treatment of small intracavernous ICAs is not advised. Large intracavernous ICAs should be considered, taking into account age and symptoms. |
Mayo Clinic College of Medicine | (1) With rare exception, all symptomatic UIAs should be treated. |
Columbia University | (1) Patients under the age of 45 should be strongly considered for treatment with exceptions being small, anterior circulation UIAs. |
Management of UIAs is characterized by an outwardly simple comparison between risk of observation and risk of intervention. However, deeper analysis shows that these situations are anything but simple. In this paper, we have summarized the patient-specific and aneurysm-specific factors that affect the natural history of these lesions. Additionally, safety and efficacy data are presented for both surgical clipping and endovascular coiling to illustrate the risks and benefits of treatment. Review of current treatment guidelines can provide practitioners with a framework to make appropriate treatment decisions when faced with UIA cases, but each patient should be approached on a case-by-case basis so as to consider the multifactorial nature of the disease.