Management of Small Unruptured Intracranial Aneurysms: A Survey of Neuroradiologists

Discussion

To our knowledge, this survey of practicing neuroradiologists and neurointerventionalists is the first of its kind to assess and quantify practice patterns regarding small unruptured aneurysms. A high degree of respondent variability is evident regarding the perception of prevalence of small UIAs, preferred imaging technique for surveillance, frequency and duration for surveillance, and optimal criteria on imaging to assess aneurysm growth and rupture risk.

Intracranial aneurysms are acquired lesions, and rupture is the most common etiology of nontraumatic SAH.^4,18 However, rupture is uncommon and only occurs in 1 of 200–400 patients with a UIA per year.⁵ The natural history of UIAs remains poorly understood, especially for the smaller (3–7 mm) and tiny (≤3 mm) aneurysms.¹⁹

A meta-analysis in 2011 including 68 studies reported a prevalence of 3.2% (95% CI, 1.9%–5.2%) in a population without comorbidity and a mean age of 50 years.¹ However, a higher prevalence of up to 7% has been reported in more recent studies using MRA, with a higher prevalence in women and with increasing age.²⁰

Regarding the prevalence of small UIAs, the survey results indicated significant heterogeneity in opinions: Nearly 40% of respondents thought small (<7 mm) aneurysms constituted <50% of all UIAs. According to a recent review, 93% of UIAs in adults are <10 mm and 66% are <5 mm.¹

Most respondents agreed that size was an important predictor of rupture, and growing aneurysms are at a higher risk for rupture. Size and location of UIAs have been recognized as predictors of rupture in prospective studies of UIAs.^6,7,21 The International Study of Unruptured Intracranial Aneurysms (ISUIA) reported no ruptures among aneurysms of <7 mm in the anterior circulation in patients with no history of SAH.⁶ However, as with most observational studies on UIAs, the ISUIA has some shortcomings, particularly related to the selection bias resulting from ablation of UIAs thought to be at high risk and conservative treatment of patients thought to be at lower risk of rupture, as well as a poor retention rate of patients used to define the natural history of aneurysms. Only 21% of patients in the observational group were followed up for >4 years. An increased risk of rupture of larger aneurysms, particularly in those measuring >7 mm in diameter, has been reported.^6,9,21,22

For assessing growth, 76% (173/227) considered that routine, periodic imaging surveillance would be appropriate for UIAs managed conservatively. Studies have proposed imaging follow-up of all aneurysms (including those of <7 mm) due to up to a 12-fold higher risk of rupture for growing-versus-nongrowing aneurysms.¹⁶ The 2015 AHA guidelines recommend a first follow-up study at 6–12 months after the initial discovery, followed by subsequent yearly or biennial follow-up (Class IIb; Level of Evidence C).⁸ However, the correlation between growth and rupture is relatively poor in small and tiny aneurysms.³ While Villablanca et al¹⁶ reported a good correlation for aneurysms of <7 mm, other studies by Sonobe et al²³ and Bor et al did not.²⁴

Respondents overwhelmingly favored MRA for imaging follow-up of small aneurysms, though 20% preferred CTA. There is considerable variability in the published literature on the optimal imaging technique used to assess growth in UIAs.^3,17 Although there is literature on the sensitivity and specificity of CTA and MRA for the detection of aneurysms, with DSA considered the criterion standard, there is a paucity of evidence on their accuracy for growth detection. Most studies do not describe interobserver reliability of measurements. Some studies used the average between 2 readers for analysis.²⁵ Other studies reported that the first and last imaging of each patient were assessed for growth in a single session by the same researcher to avoid interobserver and intraobserver reliability.²⁴

For assessing size, the change in the maximum dimension was chosen by 90% (205/227), while 24% (54/227) also chose aneurysm height. Dome-to-neck ratio, aspect ratio, and size ratio were chosen by fewer respondents. A similar degree of heterogeneity was seen in responses to criteria used to assess growth. Most respondents (73%) chose growth of >1 mm in at least 1 direction, but 16% (37/227) chose a 0.5-mm increase as clinically significant. No statistically significant difference was found in responses between diagnostic neuroradiologists and neurointerventional radiologists/endovascular neurosurgeons in size measurements on surveillance imaging and criteria used to define growth.

This variability in the definition of growth was also seen in studies reporting growth in UIAs and becomes even more significant for small UIAs.^3,17 Very few studies have used different criteria for defining growth in aneurysms of <5 mm compared with larger aneurysms.²⁶ Mehan et al²⁷ selected 2 mm as the criterion for growth in any dimension between CTA examinations because of the high degree of imprecision with smaller measurements.

In addition to size, retrospective studies have identified several morphologic parameters as potential predictors of rupture: aspect ratio (height/neck),²⁸ the bottleneck factor (dome/neck ratio),²⁹ height/width ratio,²⁹ volume-to-ostium area ratio,³⁰ and size ratio.³¹ However, the indices reported were measured after aneurysm rupture, and the results are conflicting.^32⇓–34 There is substantial variability in the definition and application of aneurysm morphology with multiple criteria, with the Unruptured Cerebral Aneurysm Study criteria reportedly having higher reliability than the ISUIA criteria.³⁵ Alternative aneurysm size definitions have been shown to have significant impact on prediction performance and optimal threshold values.³² In a prospective study, dome-to-neck ratio and multilobar morphology were found to be risk factors for growth in UIAs.²⁴ Aneurysm volume was recently reported to predict future rupture in the only long-term prospective study for UIAs.³⁴

A total of 101/227 (44%) respondents thought that small aneurysms should be routinely treated with coiling or clipping. Roughly 85% thought that surveillance imaging to assess growth should at least be annually. Although only 20% (44/227) of respondents thought that UIAs can rupture ≥10 years after they are found, nearly 60% opted for indefinite, life-long imaging surveillance. Only 20% (46/227) responded that only high-risk aneurysms should be treated or have routine imaging surveillance. Age and smoking history were chosen by more neurointerventional radiologists/endovascular neurosurgeons as criteria to treat small aneurysms. These have been shown to be risk factors for growth and rupture of UIAs.⁸

In a 2015 international survey of 203 neurosurgeons, most endorsed treatment of all asymptomatic aneurysms regardless of size.¹² A more recent North American study showed that 11% of treating physicians always or usually recommended treatment of the anterior circulation aneurysms of <5 mm without a family or personal history of SAH.¹³ Another 30% sometimes treated these small aneurysms (40%–60% of the time). A third of the respondents in our survey were practicing neurointerventionalists who treated aneurysms in clinical practice. The utility and cost-effectiveness of routine treatment or close imaging surveillance of all small UIAs are not well-established.³⁶

Surveillance imaging may not detect growth if the intervals are too far apart. Other studies have suggested that aneurysms might bleed shortly after formation, and most aneurysms without early rupture may remain stable for life, thereby questioning the rationale for prophylactic treatment of incidental small UIAs.³⁷ Significant heterogeneity in imaging follow-up protocols has been demonstrated in both untreated and treated aneurysms.^13,38

The AHA/ASA guidelines recommend that patients with documented enlargement during follow-up should be offered treatment in the absence of prohibitive comorbidities (Class I; Level of Evidence B). Long-term follow-up imaging may be considered after treatment, given the combined risk of aneurysm recurrence and de novo aneurysm formation (Class IIb; Level of Evidence B). The timing and duration of follow-up is, however, not defined for treated and untreated aneurysms, and additional investigation has been deemed necessary.⁸

Aneurysm growth is probably an irregular and discontinuous process, with potentially long periods of stability interjected with brief periods of wall instability, permitting growth or aneurysm rupture.^19,24,39 Some studies have suggested a decreased risk of aneurysm rupture after 5 years. However, in the only long-term study of patients diagnosed with UIAs between 1956 and 1978 and prospectively followed, the median time between diagnosis and a subsequent aneurysm rupture was 10.6 years (range, 1.2–24.4 years), with a median follow-up of 24.4 years.³⁴

The cost-effectiveness of screening for asymptomatic UIAs depends on multiple factors: the likelihood of UIA detection in the study population; the sensitivity and specificity of the imaging technique; the risk of rupture in conservatively followed UIAs; the cost, morbidity, and mortality associated with treatment (such as coiling or clipping); and the risk of subsequent rupture after aneurysm treatment. The AHA/ASA guidelines recommend screening in patients with ≥2 family members with intracranial aneurysms or subarachnoid hemorrhage and in patients with a history of autosomal polycystic kidney disease (Class I; Level of Evidence B).⁸

There are several limitations in interpreting the results of this survey. The survey was designed to study general imaging practices and perceptions among specialists in neuroimaging. Each aneurysm has unique characteristics, and each patient needs individual consideration. The survey did not address consideration of specific features such as aneurysm location that may significantly impact treatment decisions. An overrepresentation of neurointerventional radiologists (29%) in the respondents might bias the results toward aggressive, routine treatment of small UIAs. The study was also subject to inherent limitations of survey methodology.