It is clear that more incidental intracranial aneurysms will be encountered in the future.
Approximately 5% or more of the population harbors these lesions, and advancing technology can be expected to demonstrate them with increasing regularity.
The prevalence of Unruptured intracranial aneurysm (UIAs) in first-degree relatives of patients with aSAH in the Hong Kong Chinese population was lower than that in Caucasians. At the same time, most of the UIAs detected in this study were small (85.7% were < 5 mm, vs 66% in a meta-analysis). With a similar incidence of aSAH in Hong Kong (7.5 per 100,000 person-years) as compared with data cited in the literature, the hypothesis that UIA rupture risk size threshold is different in Chinese patients should be further investigated 1).
A better comprehension of its evolution could optimize our therapeutic strategies.
It has been shown that even small aneurysms may enlarge and bleed unpredictably with the passage of time.
Many factors are involved in management of patients with unruptured intracranial aneurysms. Site, size, and group specific risks of the natural history should be compared with site, size, and age-specific risks of repair for each patient 3).
Pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients 4).
Studies on natural history of unruptured intracranial aneurysms suggest 10 year cumulative bleeding-related mortality and severe morbidity of no less than 7.5%. In the study of Krisht et al., surgical clipping resulted in an 0.8% rate of mortality and 3.4% permanent morbidity. This suggests that surgical clipping has the potential of a superior outcome to the natural history of patients who have an estimated life expectancy of no less than 10 years 5).
In Finland and Japan, the higher incidence of subarachnoid haemorrhage is not explained by a higher prevalence of UIAs, implicating higher risks of rupture 6).
During 1995 to 2004, a period of increasing neuroimaging utilization, Gabriel et al., did not observe an increased rate of detection of unruptured brain arteriovenous malformation (BAVM), despite increased detection of unruptured intracranial aneurysm (IA)s 7).
Unruptured intracranial aneurysms (IAs) are typically asymptomatic and undetected except for incidental discovery on imaging. Blood-based diagnostic biomarkers could lead to improvements in IA management.
Preliminary findings show that RNA expression from circulating neutrophils carries an IA-associated signature. These findings highlight a potential to use predictive biomarkers from peripheral blood samples to identify patients with IAs 9).
There is notable interhospital heterogeneity in outcomes among even the largest volume unruptured intracranial aneurysm referral centers. Although further regionalization may be needed, mandatory participation in prospective, adjudicated registries will be necessary to reliably identify factors associated with superior outcomes 10).
Both UIA treatment modalities decided by one hybrid neurosurgeon showed low complication rates and good clinical outcomes. These results may serve as a point of reference for clinical decision-making for patients with UIA 11).
In a cohort of Medicare patients, there was no difference in mortality and the readmission rate between clipping and coiling of unruptured cerebral aneurysms. Clipping was associated with a higher rate of discharge to a rehabilitation facility and a longer length of stay 12).
Surgery for incidental aneurysms of the anterior circulation can be accomplished without mortality and with an operative morbidity of 6.5%. Higher morbidity occurs in surgery for aneurysms in more difficult locations as well as larger aneurysms. The increased risk of bleeding from larger aneurysms, however, may justify the increased morbidity of surgery for these lesions. Surgery for incidental aneurysms can be recommended in healthy individuals whose anesthetic risk is acceptable and for aneurysms less than 1.5 cm in diameter arising from the middle cerebral and posterior communicating arteries. Advancing age alone is not a contraindication for surgery, nor is size greater than 1.5 cm in diameter; however, the latter factor increases the operative risk. Operations to clip aneurysms of the carotid bifurcation, carotid-ophthalmic, and anterior communicating arteries may also be recommended, but these aneurysms are more difficult to approach and surgery carries a higher morbidity. Larger aneurysms, greater than 1.5 cm in diameter, in patients over 60 years of age, and in less accessible locations may not benefit from operation because surgical morbidity for these lesions is high and with advancing age the lifetime risk of rupture has decreased. For incidental aneurysms of the posterior circulation there are insufficient data to make a recommendation regarding surgery, although it is anticipated that the counsel for anterior circulation aneurysms will apply. If operative mortality and morbidity are to be maintained at acceptable levels, incidental aneurysm surgery should be the province of the accomplished aneurysm surgeon who has available to him the most modern techniques and equipment. With the clipping of incidental aneurysms, hopefully the number of patients suffering from subarachnoid hemorrhage with its high morbidity and mortality rates can be further reduced 13).
Patients' life expectancy, risk of rupture, and utility of awareness of an untreated aneurysm mainly define cost-effectiveness. However, important uncertainties remain on the rupture risk according to size and location of the aneurysm and on the utility of awareness of untreated aneurysm. More data on these factors are needed to define and individualize cost-effectiveness analyses 14).
The results of a study demonstrate the importance of taking the preinterventional psychiatric history into considerations when evaluating the outcome after unruptured aneurysm treatment. The unfavorable outcome of the aneurysm group seems to be caused by factors that are not related the aneurysm diagnosis or treatment itself 16).
A series of 296 UIA patients (including 162 treated and 134 untreated) were analyzed. Postal questionnaires were sent to these patients, included Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale(SDS) and Short Form-36(SF-36). In total, 198 (66.9%) patients responded to our questionnaires. Patients with surgical clipping or endovascular coiling had a significant improvement in the physical function, body pain and mental health domains. No significant difference in the SAS, SDS and SF-36 was observed between the clipping and coiling group, while SF-36 in body pain domain was significant higher in the coiling group. Moreover, patients diagnosed 5years ago with or without treatment got lower score of SAS and SDS, higher SF-36 score than those diagnosed one year ago. Neurological complications may be an important factor causing lower quality of life. The QoL of patients with endovascular coiling appear to be better than those of surgical clipping, with no difference in anxiety or depression 17).
8705 patients underwent treatment for unruptured intracranial aneurysms.
Of these patients, 2585 (29.7%) had surgical clipping and 6120 (70.3%) had endovascular coiling. Instrumental variable analysis demonstrated no difference between coiling and clipping in 1-year postoperative mortality (OR 1.25, 95% CI 0.68-2.31) or 90-day readmission rate (OR 1.04, 95% CI 0.66-1.62). However, clipping was associated with a greater likelihood of discharge to rehabilitation (OR 6.39, 95% CI 3.85-10.59) and 3.6 days longer length of stay (LOS; 95% CI 2.90-4.71). The same associations were present in propensity score-adjusted and inverse probability-weighted models.
In a cohort of Medicare patients, there was no difference in mortality and the readmission rate between clipping and coiling of unruptured cerebral aneurysms. Clipping was associated with a higher rate of discharge to a rehabilitation facility and a longer length of stay 18).
Over an 11.5-year period, Serrone et al, recommended surveillance imaging to 192 patients with 234 UIAs. The incidence of UIA growth and de novo aneurysm formation was assessed. With logistic regression, risk factors for UIA growth or de novo aneurysm formation and patient compliance with the surveillance protocol was assessed.
During 621 patient-years of follow-up, the incidence of aneurysm growth or de novo aneurysm formation was 5.0%/patient-year. At the 6-month examination, 5.2% of patients had aneurysm growth and 4.3% of aneurysms had grown. Four de novo aneurysms formed (0.64%/patient-year). Over 793 aneurysm-years of follow-up, the annual risk of aneurysm growth was 3.7%. Only initial aneurysm size predicted aneurysm growth (UIA < 5 mm = 1.6% vs UIA ≥ 5 mm = 8.7%, p = 0.002). Patients with growing UIAs were more likely to also have de novo aneurysms (p = 0.01). Patient compliance with this protocol was 65%, with younger age predictive of better compliance (p = 0.01).
Observation of low-risk UIAs with surveillance imaging can be implemented safely with good adherence. Aneurysm size is the only predictor of future growth. More frequent (semiannual) surveillance imaging for newly diagnosed UIAs and UIAs ≥ 5 mm is warranted 19).
A prospective consecutive cohort of 292 patients (2006-2014) and 368 SUIAs (anterior circulation aneurysms (ACs) smaller than 7 mm and posterior circulation aneurysms smaller than 4 mm without previous subarachnoid haemorrhage) was observed (mean follow-up time of 3.2 years and 1177.6 aneurysm years). Factors associated with aneurysm growth were systematically reviewed from the literature.
The aneurysm growth probability was 2.6±0.1% per year. The rate of unexpected aneurysm rupture before treatment was 0.24% per year (95% CI 0.17% to 2.40%). The calculated rate of aneurysm rupture after growth was 6.3% per aneurysm-year (95% CI 1% to 22%). Aneurysms located in the posterior circulation and aneurysms with lobulation were more likely to grow. Females or patients suffering hypertension were more likely to have an aneurysm growing. The probability of aneurysms growth increased with the size of the dome and was proportional to the number of aneurysms diagnosed in a patient.
It is safe to observe patients diagnosed with SUIAs using periodic imaging. Intervention to secure the aneurysm should be performed after growth is observed 20).
Bekelis et al performed a cohort study of 100% Medicare fee-for-service claims data for elderly patients who underwent treatment for unruptured cerebral aneurysms from 2007 to 2012. In order to control for measured confounding we used multivariable regression analysis with mixed effects to account for clustering at the Hospital Referral Region (HRR) level. An instrumental variable (regional rates of endovascular treatment) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method.
During the study period 8705 patients underwent treatment for unruptured cerebral aneurysms and met the inclusion criteria. Of these, 2585 (29.7%) had surgical clipping and 6120 (70.3%) had endovascular treatment. The median total Medicare expenditures in the first year after the admission for the procedure were $46 800 (IQR $31 000-$74 400) for surgical clipping and $48 100 (IQR $34 500-$73 900) for endovascular therapy. When we adjusted for unmeasured confounders, using an instrumental variable analysis, clipping was associated with increased 7-day Medicare expenditures by $3527 (95% CI $972 to $5736) and increased 1-year Medicare expenditures by $15 984 (95% CI $9017 to $22 951).
In a cohort of Medicare patients, after controlling for unmeasured confounding, we demonstrated that surgical clipping of unruptured cerebral aneurysms was associated with increased 1-year expenditures compared with endovascular treatment 21).
198 unruptured cerebral aneurysms for whom clinical observation and follow-up with imaging surveillance was recommended at 4 clinical centers were prospectively recruited into this study. Imaging data (predominantly CT angiography) at initial presentation was recorded. Computational geometry was used to estimate numerous metrics of aneurysm morphology that described the size and shape of the aneurysm. The nonlinear, finite element method was used to estimate uniform pressure-induced peak wall tension. Computational fluid dynamics was used to estimate blood flow metrics. The median follow-up period was 645 days. Longitudinal outcome data on these aneurysm patients-whether their aneurysms grew or ruptured (the unstable group) or remained unchanged (the stable group)-was documented based on follow-up at 4 years after the beginning of recruitment.
Twenty aneurysms (10.1%) grew, but none ruptured. One hundred forty-nine aneurysms (75.3%) remained stable and 29 (14.6%) were lost to follow-up. None of the metrics-including aneurysm size, nonsphericity index, peak wall tension, and low shear stress area-differentiated the stable from unstable groups with statistical significance.
The findings in this highly selected group do not support the hypothesis that image-derived metrics can predict aneurysm growth in patients who have been selected for observation and imaging surveillance. If aneurysm shape is a significant determinant of invasive versus expectant management, selection bias is a key limitation of this study 22).
One thousand twelve patients with 1440 UIA underwent 1080 craniotomies. 10.1% (95% confidence interval [CI], 8.4-12.0) of craniotomies resulted in a complication leading to a modified Rankin Scale score >1 at 12 months. Logistic regression found age (odds ratio, 1.04; 95% CI, 1.02-1.06), size (odds ratio, 1.12; 95% CI, 1.09-1.15), and posterior circulation location (odds ratio, 2.95; 95% CI, 1.82-4.78) to be significant. Cumulative 10-year risk of retreatment or rupture was 3.0% (95% CI, 1.3-7.0). The complication-effectiveness model was derived by dividing the complication risk by the 10-year cumulative freedom from retreatment or rupture proportion. Risk per effective treatment ranged from 1% for a 5-mm anterior circulation UIA in a 20-year-old patient to 70% for a giant posterior circulation UIA in a 70-year-old patient.
Complication-effectiveness analyses increase the information available with regard to outcome for the management of UIAs 23).
Of 1231 UIAs in 1124 patients, 625 (50.7 %) aneurysms were treated with surgery, and 606 (49.3 %) aneurysms were treated with EVT. The overall complication rate of UIA treatment was 3.2 %. The rate of adverse events was 2.4 %, and the rates of morbidity and mortality were 0.6 and 0.2 %, respectively. The rates of adverse events, morbidity, and mortality were not significantly different between surgery and EVT. The rate of hospital use for EVT was stationary over the years of the study. Posterior circulation in surgery, large aneurysms (>15 mm) in EVT, and stent- or balloon-assisted procedures in EVT were associated with the occurrence of complications. Poor clinical outcome (mRS of 3-6) was 0.8 % at hospital discharge 24).