Unruptured intracranial aneurysms: An updated review of current concepts for risk factors, detection and management

NEUROL-1794; No. of Pages 10 revue neurologique xxx (2017) xxx–xxx

Available online at

ScienceDirect www.sciencedirect.com

General review

Unruptured intracranial aneurysms: An updated review of current concepts for risk factors, detection and management G. Boulouis a,b, C. Rodriguez-Re´gent a,b, E.C. Rasolonjatovo c, W. Ben Hassen a,b, D. Trystram a,b, M. Edjlali-Goujon a,b, J.-F. Meder a,b, C. Oppenheim a,b, O. Naggara a,b,* a

Service d’imagerie morphologique et fonctionnelle, hoˆpital Sainte-Anne, 1, rue Cabanis, 75014 Paris, France Inserm U894, universite´ Paris-Descartes, 12, rue de l’E´cole-de-Me´decine, 75270 Paris cedex 06, France c Service de neurochirurgie, centre hospitalier universitaire Joseph-Ravoahangy-Andrianavalona (CHU-HJRA), Antananarivo, Madagascar b

info article

abstract

Article history:

The management of patients with unruptured intracranial aneurysms (UIAs) is a complex

Received 5 October 2016

clinical challenge and constitutes an immense field of research. While a preponderant

Received in revised form

proportion of these aneurysms never rupture, the consequences of such an event are severe

3 December 2016

and represent an important healthcare problem. To date, however, the natural history of

Accepted 12 May 2017

UIAs is not completely understood and there is no accurate means to discriminate the UIAs

Available online xxx

that will rupture from those that will not. Yet, a good understanding of the recent evidence

Keywords:

to the given patient’s level of risk and psychoaffective status. Thus, this review addresses

Intracranial aneurysm

the current concepts of epidemiology, risk factors, detection and management of UIAs.

and future perspectives is needed when advising a patient with IA to tailor any information

# 2017 Elsevier Masson SAS. All rights reserved.

Imaging Prognosis Endovascular Subarachnoid hemorrhage Unruptured aneurysm

1.

Introduction

An intracranial aneurysm is an acquired focal outpouching (typically either saccular or fusiform) of a cerebral artery wall [1]. Its most feared complication is rupture, causing blood to erupt into the subarachnoid space with potentially fatal and frequently disabling outcomes [2,3]. The consequences of an

aneurysmal subarachnoid hemorrhage (aSAH) are devastating, with at least a quarter of such patients not surviving the rupture or its immediate complications, while leaving roughly half the survivors with permanent disabling neurological deficits [4]. With the greater availability of technical improvements and the ever-widening indications for noninvasive vascular neuroimaging [5], unruptured intracranial aneurysms (UIAs) are increasingly being discovered incidentally and an steadily

* Service d’imagerie morphologique et fonctionnelle, hoˆpital Sainte-Anne, 1, rue Cabanis, 75014 Paris, France. E-mail address: [email protected] (O. Naggara). http://dx.doi.org/10.1016/j.neurol.2017.05.004 0035-3787/# 2017 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Boulouis G, et al. Unruptured intracranial aneurysms: An updated review of current concepts for risk factors, detection and management. Revue neurologique (2017), http://dx.doi.org/10.1016/j.neurol.2017.05.004

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growing number of patients are being referred to or seeking counseling from specialized centers regarding opportunities for screening (for example, for fear of occult UIAs after a relative has suffered an aSAH) [6]. However, UIAs represent a challenging situation to manage for several reasons:  while the vast majority of UIAs never rupture [7–9], the consequences of such an event are severe and represent a major healthcare problem [4,10];  the natural history of UIAs is still not entirely understood and there is no accurate way to discriminate UIAs likely to rupture from those that will not [11,12];  the currently available treatments for repairing UIAs are invasive and associated with non-trivial morbidity, a risk particularly relevant in previously asymptomatic patients [13];  the popular belief that an UIA is an imminent and everpresent peril has important psychosocial effects in patients with identified but untreated UIAs [14,15]. Therefore, screening might, in some cases, not achieve its ultimate goal of improving quality years of life. As a consequence, when offering screening for UIAs or advising for interventional vs. conservative management in patients with UIAs, physicians face a complex situation where no option is risk-free. The optimal management and counseling should therefore focus on tailoring each encounter to the patient’s specific level of risk and psychoaffective status, based on the available (albeit incomplete) evidence. The American Heart Association (AHA)/American Stroke Association (ASA) issued guidelines for the management of UIAs in 2015 [16]. The present review does not intend to provide further guidelines, but aims to address the latest evidence on the epidemiology, natural history, risk factors, clinical and imaging presentations, treatment and follow-up of UIAs.

2.

Epidemiology and natural history

2.1.

Epidemiology

The reported prevalence of UIAs varies by assessment modality [magnetic resonance imaging (MRI), computed tomography (CT), conventional angiography, autopsy] and subpopulation sampling, but remains rather consistently between 2% and 6% [17–20]. The largest epidemiological study to date, published in 2011 [18], aggregated the results of 68 studies in a metaanalysis of 94,912 patients with 1450 UIAs. In their report, the investigators estimated the prevalence of UIAs in a fictitious population, with a mean age of 50 years and 50% male, at 3.2% (95% CI: 1.9–5.2%). The study showed that the prevalence of UIAs was influenced by the presence of polycystic disease, a positive family history, older age and female gender, but did not differ across geographical regions [18]. In particular, they found no higher prevalence of UIAs in Japan and Finland (an issue that has triggered intense debates over the past decades) [21,22].

There are only very scanty data available on incident UIAs, as they would require extensive long-term longitudinal studies with repeated imaging assessments in large populations [16]. In one recent study carried out in patients already diagnosed with at least one saccular IA, the cumulative incidence of de novo formation of UIAs was estimated to be as low as 0.23% per patient–year [23]. However, more studies are needed to confirm this estimate in different settings.

2.2.

Natural history

The natural history of UIAs is currently conceptualized as a sequential process in which:  the UIA develops;  the UIA evolves (with morphological and size changes);  the UIA ruptures, or not [13]. Temporal characteristics of the process are as yet poorly understood. Although much remains to be elucidated to understand why some UIAs evolve and rupture while others do not, there have nonetheless been some remarkable advances in the field of UIA research, leading to evidence that the genesis of IAs include flow-driven inflammatory and wall-remodeling processes [24,25]. There is also strong evidence that UIAs differ pathologically from those that have ruptured, with the latter presenting with more histological, structural and molecular feed-forward wall-weakening processes [26]. Understanding the mechanisms responsible for the initiation and maintenance of these processes would add tremendous insight to our current understanding of UIA natural history and perhaps even lead to accurate prediction of the risk of rupture. At the population level, previous studies, including the large International Study of Unruptured Intracranial Aneurysms (ISUIA) [27], have demonstrated that UIAs have a totally different evolution in patients with vs. without a history of aSAH compared with other IAs. In the study, the annualized risk of rupture was  0.05% in patients with no history of aSAH, whereas it was close to 11-fold higher in those with a previous aSAH (0.55%). More recently, a large prospective cohort study of 2252 patients with a cumulative total of 7388 aneurysm–years found an overall rupture incidence of 0.76% per year (95% CI: 0.58–0.98%), which was significantly increased for aneurysms  10 mm with daughter sacs, and for UIAs located in the vertebrobasilar and internal carotid– posterior communicating arteries [28], which was in line with previously reported findings [29,30]. However, the only ‘‘lifelong’’ longitudinal study was conducted in Finland and included 118 patients, with a total follow-up until death or an aSAH of 2187 person–years. In this study of patients aged 51.3 years on average at inclusion, almost 30% of UIAs ruptured over a median 18.5 years of follow-up, and 25% of patients with UIAs < 7 mm in size suffered an aSAH, thus yielding much higher annualized estimates. Yet, the question of the external validity of such studies, which have included only Finnish (and Japanese patients), has been consistently raised [21], leading to their

Please cite this article in press as: Boulouis G, et al. Unruptured intracranial aneurysms: An updated review of current concepts for risk factors, detection and management. Revue neurologique (2017), http://dx.doi.org/10.1016/j.neurol.2017.05.004

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exclusion from any large pooled analyses of observational studies [31]. Nevertheless, while there may be no perfect setting in which to evaluate the true rate of UIA ruptures, there is a genuine need for international long-term observational studies.

2.3.

Risk factors

The risk factors for UIAs parallel their natural history and can be schematically categorized as:  risk of UIA occurrence/development;  risk of UIA evolution (in morphology and/or size);  risk of rupture.

2.3.1.

For UIA occurrence

Very few longitudinal studies exploring UIA risk factors have been performed in the general population or case–control series [20]. Thus, the currently available evidence mostly derives from either patients with aSAH, high-risk screened populations or observational clinical series [7,28–30,32–34], which is important to bear in mind when appraising the reviewed data.

2.3.1.1. Female gender and older age. Consistent increases in the risk of UIA occurrence have been reported in women. In a large meta-analysis of 83 study populations (from publication years 1952–1996) published in 2011 [18], the female/male prevalence ratio was calculated as 1.61 (95% CI: 1.02–2.54), increasing to 2.2 (95% CI: 1.3–3.6) in study populations with a mean age > 50 years. The reason for this gender asymmetry (which was even more pronounced for aSAH) [35,36] is not clear. It has been hypothesized that peri- and postmenopausal estrogen concentration decreases may confer an increased risk of IA pathogenesis [37]. Otherwise, older age, with peaks during the fifth and sixth decades [18,38], has also proved to be a constant, non-modifiable risk factor for UIAs. 2.3.1.2. Modifiable risk factors. The most well established modifiable risk factors for UIAs are smoking [39] and elevated blood pressure [27,40,41]. Current or former smoking has been reported in rates ranging from 15–79% in UIA bearers [39], and numerous reports have linked smoking to UIAs [30], potentially mediated by chronic inflammatory mechanisms [42]. Elevated blood pressure is also consistently found to increase the risk of UIA occurrence, growth and rupture [16,41]. The role of excessive alcohol intakes has also been suggested [43], but is less clear. Of note, while these risk factors are essentially modifiable, the impact of their modification on the evolution of risk of UIA development and rupture is still unknown [16]. 2.3.1.3. Family and genome. The role of genetic factors in the pathogenesis of IAs has been suggested by a number of studies reporting familial preponderances of IAs, as well as direct genetic-disorder associations. Familial aggregations of IAs have been estimated to arise in 7–20% of cases [44–46] and it appears that first-degree relatives (FDRs) of patients with an IA (whether ruptured or not) are at higher risk of IAs [44]. In the

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Familial Intracranial Aneurysm (FIA) study, for instance, of the patients aged  30 years with a history of either hypertension or smoking, the detection rate of IA in families with at least two FDRs affected by IAs (therefore considered ‘‘high-risk’’ patients) was 19.1%, and was even higher in women than in men [47]. However, the inheritance pattern of IAs is still unclear and the accumulating evidence suggests that the ‘‘familial’’ forms of UIAs are largely driven by environmental factors (which can ‘‘run through’’ families) and are mostly non-genetic in nature [48,49]. Indeed, the Nordic Twin Study found that the corresponding risk of aSAH in monozygotic twins is only 5.9% [48]. Thus, while the vast majority of ‘‘familial’’ forms of UIAs are not explained by genetic heritability, candidate gene testing and genome-wide association studies (GWAS) have yet to identify any multiple loci and genes directly or indirectly associated with IAs [49–52]. Notably, in such studies, most of the single-nucleotide polymorphisms (SNPs) associated with IA have been linked to genes differentially expressed in smooth muscle and endothelial cells that regulate cell-cycle progression and cellular proliferation and, therefore, are most likely implicated in vasculogenesis and vascular repair [51]. Future studies combining GWAS and environment-wide association study (EWAS) data are likely to shed light on the interactions between environmental, ‘‘familial’’ and genetic factors in the genesis of IAs.

2.3.1.4. Hereditary and congenital syndromes. Some lesscommon hereditary disorders are also known to carry significantly increased risks of both IA occurrence and rupture. Among them most notably are the autosomal form of polycystic kidney disease [18,53], and connective tissue disorders such as Ehlers–Danlos type IV and pseudoxanthoma elasticum [54] (but not Marfan’s syndrome) [55], which have been shown to increase UIA prevalence and to confer a significant risk of rupture. Patients with microcephalic osteodysplastic primordial dwarfism [56] and with aorta coarctation [57] are also known to have significantly higher rates of UIA prevalence. 2.3.2. For UIAs growth and rupture 2.3.2.1. UIA growth. A recent meta-analysis of 3954 patients with 4990 aneurysms found that patient risk factors for growth included older age (> 50 years), female gender and a history of smoking, whereas aneurysm risk factors included a cavernous carotid location, non-saccular shape and larger initial size [33]. Advanced imaging biomarkers, including aneurysm wall enhancement, are also being investigated as potential markers of aneurysm change/stability (Fig. 1) [58]. Another important factor is that the growth rate of UIAs is believed to be a non-linear phenomenon [59], with periods with and without aneurysm growth resulting in periods of higher and lower risk of rupture [60].

2.3.2.2. UIA rupture. Risk factors for aneurysm rupture vary primarily by aneurysm size (> 7–10 mm), location (posterior locations are overrepresented) and growth, smoking, female gender and a history of hypertension (treated or not). Younger age, aneurysm morphology and a previous personal or family

Please cite this article in press as: Boulouis G, et al. Unruptured intracranial aneurysms: An updated review of current concepts for risk factors, detection and management. Revue neurologique (2017), http://dx.doi.org/10.1016/j.neurol.2017.05.004

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which accumulated 1.26 million person–years of follow-up, in which the authors found that female smokers with raised systolic blood pressure had > 20 times the risk of aneurysm rupture than normotensive, non-smoking, age-matched males [61]. More important, while larger UIAs (> 10 mm) are systematically found to be at higher risk of rupture, the considerably greater prevalence of smaller UIAs explains why most ruptures involve UIAs < 10 mm, considered by some to be the ‘critical size’ for risk of rupture [62–65]. Promising predictors of aneurysm rupture include morphological characteristics such as size ratio and geometric parameters (non-sphericity index, aneurysm angle) [66,67], although the lack of standardization of assessment method makes these factors harder to evaluate in larger sample populations.

3.

Fig. 1 – Aneurysm wall enhancement in a 45-year-old man screened after a first-degree relative suffered aneurysmal subarachnoid hemorrhage. (A) Volume rendering of 3D time-of-flight magnetic resonance angiography reveals a saccular aneurysm in the first segment of the middle cerebral artery (MCA; white arrowhead), which is better appreciated on (B, white arrowhead) raw sagittal images showing (C) circular wall enhancement (white dashed line). The patient was treated by simple coiling. However, a smaller left MCA aneurysm was not invasively treated, but was instead deemed appropriate for follow-up.

history of aSAH have also been shown to significantly increase the risk of aSAH [29,40]. A representative example of the effect of gender, smoking and hypertension comes from a large-scale longitudinal study,

Screening

Screening policies for UIAs have been evaluated by costeffectiveness or value-based approaches [68] in which the estimated financial burden of implementing screening was weighed against morbidity–mortality risks, and the direct and indirect financial consequences, of discovering a UIA. In studies evaluating the quality-adjusted life years in various settings, value-based screening policies had characteristics that seemed favorable only in populations at high risk (those with higher UIA prevalences and higher risks of rupture) [69–71]. As a consequence, screening for occult UIAs is systematically recommended only for patients considered at high-risk of UIAs—that is, those with  two FDRs with either a UIA or aSAH, and patients with hereditary syndromes with significant risks of UIA occurrence (including autosomal polycystic disease and Ehlers–Danlos type IV if one or more FDRs had an aSAH or is known to harbor a UIA) [16]. Based on lower-level evidence, it is also advisable to screen patients with microcephalic osteodysplastic primordial dwarfism [56] as well as patients with aorta coarctation [57], given their higher UIA prevalence and risks of rupture. Other conditions, such as sickle cell disease and high-flow brain vascular malformations also carry greater risks of aneurysm formation and rupture, although screening modalities for these have yet to be established [72].

4.

Clinical imaging presentations

An important cause of UIA discovery is an aSAH due to another IA [27]. In the absence of hemorrhage, UIAs are commonly asymptomatic and may only be discovered during workups of various unrelated or non-specific conditions, including headaches in particular [73].

4.1.

Clinical symptoms

4.1.1.

Headaches

Non-specific headaches arise in about one-third to one-half of UIA carriers [27,29,32] and have been reported in almost all

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Fig. 2 – Symptomatic unruptured intracranial aneurysm (UIA) treated by flow diversion in a 60-year-old woman with chronic headaches and recent progressive oculomotor palsy. After an adequate initial workup, the giant right intracavernous carotid aneurysm, seen on (A) conventional angiography (white arrowhead), was treated with (B) a flow diverter (the golden stent-like mesh), with complete occlusion seen on (C) the 1-month computed tomography angiography follow-up (black arrowhead).

series of UIAs and, therefore, represent the most common clinically overt symptom prompting imaging (Fig. 2). Although the causal link between UIAs and non-specific headaches is not well characterized, at least two studies have demonstrated, in different populations, a significant improvement in headaches after UIA repair [74,75]. Greater suspicion is warranted for new-onset acute headaches, including thunderclap presentations, which have been reported to precede from 10% to as much as 50% of aneurysm ruptures [76], which is why they are referred to as ‘‘sentinel headaches’’. Alternative pathophysiological mechanisms (including sudden dissection of aneurysm walls, aneurysm growth and intrasaccular thrombosis) have been suggested to account for the appearance of sudden-onset headaches in the absence of eventual aneurysm rupture [77].

4.1.2.

Isolated cranial nerve palsy

Another common, but much more specific, clinical manifestation of UIAs is the occurrence of isolated third cranial nerve palsy [78], the result of either direct compression of a posterior carotid artery aneurysm or, more rarely, UIA in a basilar artery tip. Even with symptoms as mild as an isolated mydriatic pupil, the onset of third cranial nerve palsy requires emergency neuro-ophthalmological evaluation and should raise concerns regarding imminent aneurysm rupture [79].

4.1.3.

Ischemic stroke

More rarely, when found upstream of an ischemic territory and typically when imaging demonstrates intrasaccular thrombosis, UIAs have been implicated as potential sources of embolic material in ischemic stroke patients [80]. However, the consequences of long-term preventative strategies, including antithrombotic use, in this specific subgroup of patients are unknown.

exposure. While digital subtraction angiography (DSA) remains the gold standard for intracranial vascular imaging, technical advances in CT and magnetic resonance angiography (MRA) have considerably narrowed down its indications.

4.1.4.

4.1.5.

clinical situation. Routine screening should use a highly sensitive method, but preferably with the least radiation

Magnetic resonance angiography

Time-of-flight and contrast-enhanced MRA has proved accurate for the detection of aneurysms > 3 mm, with sensitivity close to that of CTA [87]. In addition, recent work has shown that even aneurysms < 5 mm can accurately be imaged with a 3-Tesla magnet [88]. However, MRA limitations include its lower sensitivity for small aneurysms and, as with CTA, its inferior ability to characterize UIA morphology [89]. Nevertheless, overall, the lack of radiation with MRA without a need for contrast-media injections and its adequate detection capacity makes it the preferred option for screening UIAs and, even more so, their follow-up (which should be performed under similar scanning conditions).

4.1.6. 4.1.3.1. Imaging UIAs. The modality selected depends on the

Computed tomography

Technical advances such as multidetector CT angiography (CTA) have made this modality a reasonable option for UIA detection and initial screening. Recent studies have shown that CTA has excellent detection capacities (and, more important, very high sensitivity) even for smaller aneurysms [81–84]. Moreover, CTA allows detection of neck and wall calcifications as well as thrombus, all-important factors when planning treatment [85]. However, it is important to note that, while being a good tool for screening, three-dimensional (3D) reconstruction algorithms are known to alter representations of the aneurysm neck and the immediately adjacent small arterial branches, thereby rendering CTA in some instances inadequate for treatment decision-making [86].

Conventional angiography

DSA has proved to be, in various studies, the most sensitive modality, especially for smaller aneurysms [83,87,90,91] and, thus, continues to be the gold standard for IA characterization

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and detection. However, being invasive, its role in routine aneurysm detection seems unjustified [92]. On the other hand, DSA can be used to further characterize morphological characteristics of complex aneurysms for pretreatment planning or to resolve inconsistent findings with noninvasive imaging methods (such as discriminating smaller aneurysms from infundibuliform structures). Furthermore, DSA is probably mandatory when a conservative approach is not an obvious choice for depicting multiple aneurysms or for precisely characterizing aneurysms from an anatomical point of view (overall size, neck size, daughter sacs).

5.

Treatment

Treatment of UIAs aims to exclude its lumen from the circulating intracranial vessels to prevent bleeding. This can be achieved by external (surgical) clipping of the aneurysm at its neck or by packing the lumen of the aneurysm with metal coils (and/or diverting blood flow by placing a stent to block aneurysm inflow) [93].

5.1.

Endovascular treatment

Various options are available when treating UIAs by endovascular means, including coiling, stents, balloon-assisted coiling, and flow diversion and flow disruption [94]. In 2002, the large International Subarachnoid Aneurysm Trial (ISAT) found a significant survival advantage and good functional outcome for patients treated with coiling vs. surgery [95], findings that were recently confirmed after 10 years of followup [96]. Since the publication of that landmark trial, there has been a constant increase in the proportion of patients treated with coil embolization. However, to date, no randomized trial has specifically investigated the differences in outcomes of patients with UIAs treated surgically vs. endovascular techniques (EVTs). The first prospective study – the Analysis of Treatment by Endovascular Approach of Non-Ruptured Aneurysms (ATENA) [97] conducted in France and Canada – showed that endovascular treatment of UIAs was feasible and associated with low morbidity–mortality. Specifically, the authors found that adverse events were associated with either transient or permanent neurological deficits in 5.4% of the 649 patients (1000 aneurysms) treated by EVTs, with 1-month morbidity and mortality of 1.7% and 1.4%, respectively. More recently, a systematic review and meta-analysis of 85 articles (comprising 225,772 patients) confirmed that patients treated with coiling had higher rates of favorable outcomes and lower mortality than those treated surgically [98]. Older patients with aneurysms > 10 mm, core areas and cerebral ischemic comorbidities have also been shown to have overall higher risks of per-procedural complications [99]. The most commonly reported caveat with EVTs is the higher rate of aneurysm revascularization (or recurrence) compared with surgical techniques, which are especially prevalent in patients with incomplete initial occlusion and can sometimes happen after prolonged delays [100]. The current AHA/ASA guidelines, in turn, highlight the importance of regular surveillance and treatment of recurrences [16,101].

Overall, in the 15 years since the confirmation of EVTs as safe and efficient, the outcomes in patients treated for IAs have significantly improved [102] and similar trends have been observed in patients receiving endovascular treatments [103].

5.2.

Surgical treatment

Another available approach is direct surgical clipping of the aneurysm by placing a metal clip on its neck. This technique has been consistently associated with lower rates of recurrence but, as mentioned above, greater morbidity–mortality, making it a good choice only for patients deemed unsuitable for endovascular coiling [95,104]. Some factors have been found to increase the risk of per-procedural surgical complications, most notably, large size (> 12 mm), posterior localization and older age of the patient [13,105]. With the evolution of surgical techniques and the possibility of using combined approaches (per-procedural angiography and ultrasound, for example), the risk with surgical approaches for UIAs has been lower in recent studies [106]. Based on these data, the current guidelines favoring endovascular treatment over surgical clipping is only for selected UIAs [16], especially cases where surgical clipping is predicted to carry excess morbidity (posterior circulation, larger size, older population) and aneurysm anatomy is likely to result in near-complete coil obliteration (Fig. 2 and Fig. 3).

5.3.

Treatment strategy

When advising a patient on conservative vs. interventional management of UIAs, the clinician is faced with a complex challenge. On the one hand, the above-mentioned risk factors for aneurysm rupture have been widely studied in various populations but, on the other hand, only one study, from Finland [40], assessed the long-term risk of aneurysm rupture. Likewise, it is possible that the long-term risk of rupture can be extrapolated from 5-year estimates (multiplied to advise patients on their 10- and 20-year risks accordingly). The main caveat of this approach is that the rate of growth (and, thus, risk of rupture) is likely to be inconsistent over time [59] (see below). Decision-making and patient counseling therefore relies on several factors to balance the estimated risk of rupture against the estimated risk of treatment-related complication. Factors to take into account include patient age (and life expectancy), aneurysm location, size and shape, comorbidities, aneurysm growth and morphological changes as well as estimated treatment risk. In fact, these elements have been factored into two main scoring systems, the UIA Treatment Score [107] and the PHASES Score [108], which may be helpful when advising patients on either option. However, these should be used with caution, given the uncertainties of UIA prediction models. More important, one factor not accounted for is the psychosocial consequences of patients discovering they have untreated UIAs. As the treatment decision (whether conservative or interventional) is ultimately up to the patient, it is important to clearly explain why either option is preferred by the care team and to make sure that the patient understands that such decisions are based on the balanced estimated, and not actual, risks [60,99,107,108].

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Fig. 3 – Saccular middle cerebral artery (MCA) aneurysm treated by coiling in a 56-year-old woman with a 7-mm left MCA bifurcation aneurysm seen on (A) 3D volume rendering by conventional angiography (white arrowhead) and (B) conventional angiography of the left internal carotid artery (white arrowhead). The aneurysm was treated by (C, left) simple coiling (black arrowhead points to packed coils), resulting in complete aneurysm occlusion, with no residual flow on (C, right) per-procedural control angiography.

6.

Follow-up

The overarching goal of UIA follow-up is to prevent rupture by detecting factors that may portend high risk (such as aneurysm growth or morphological evolution), or detecting recurrence or the evolution of aneurysm remnants after treatment. Follow-up in rare instances may also detect de novo (newly formed) aneurysms. However, no study has explored the optimal follow-up interval after discovering an UIA or which modality should be preferred for such purposes. Most of the available work indicates that the initial follow-up imaging should be done within 1 year and be continued annually or biannually until total stability is documented [109]. What remains unanswered is the point at which UIA follow-up should be completely discontinued, a decision that remains at the clinician’s discretion after weighing the expected benefits against the burdens on the patient and healthcare system. CTA and MRA appear to be reasonable options, but the former, being associated with radiation exposure over time, may not be preferred, especially in younger patients who have potentially longer follow-up durations [36]. In a recent review by Soize et al. [110], the authors carefully addressed the specifics of aneurysm follow-up after endovascular treatment. In this case, the authors suggested that MRA is a suitable modality for follow-up of coiled UIAs. However, no evidence could be derived from this work for follow-up intervals. A recent study showed significant heterogeneity across academic centers in the US in terms of imaging follow-up strategies after treatment, with wide variations in the resultant costs (from $3300+ to $46,000 + ), suggesting a need for stratification of follow-up strategies by recanalization risk [111]. This idea has been supported by a long-term study showing that a significant proportion (11.4%, 99% CI: 7.0–18.0%) of initially occluded aneurysms were found to recur > 10 years after endovascular treatment. As the long-term bleeding rate is reported to be low (0.7%, 99% CI: 0.2–2.7%), follow-ups lasting > 10 years may be necessary for patients with aneurysms > 10 mm or with incompletely occluded aneurysms after endovascular treatment [100].

7.

Conclusion

UIAs represent a complex clinical situation. However, despite tremendous progress in the field, many questions have yet to be answered before it becomes possible to optimally advise, treat and follow these patients.

Disclosure of interest The authors declare that they have no competing interest.

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