Clinical, radiological, and flow-related risk factors for growth of untreated, unruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: Unruptured intracranial aneurysms are frequently followed to monitor aneurysm growth. We studied the yield of follow-up imaging and analyzed risk factors for aneurysm growth. METHODS: We included patients with untreated, unruptured intracranial aneurysms and ≥6 months of follow-up imaging from 2 large prospectively collected databases. We assessed the proportion of patients with aneurysm growth and performed univariable and multivariable Cox regression analyses to calculate hazard ratios with corresponding 95% confidence intervals (CI) for clinical and radiological risk factors for aneurysm growth. We repeated these analyses for the subset of small (<7 mm) aneurysms. RESULTS: Fifty-seven (12%) of 468 aneurysms in 363 patients grew during a median follow-up of 2.1 years (total follow-up, 1372 patient-years). In multivariable analysis, hazard ratios for aneurysm growth were as follows: 1.1 (95% CI, 1.0-1.2) per each additional mm of initial aneurysm size; 2.7 (95% CI, 1.2-6.4) for dome > neck ratio; 2.1 (95% CI, 0.9-4.9) for location in the posterior circulation; and 2.0 (95% CI, 0.8-4.8) for multilobarity. In the subset of aneurysms <7 mm, 37 of 403 (9%) enlarged. In multivariable analysis, hazard ratios for aneurysm growth were 1.1 (95% CI, 0.8-1.5) per each additional mm of initial aneurysm size, 2.2 (95% CI, 1.0-4.8) for smoking, 2.9 (95% CI, 1.0-8.5) for multilobarity, 2.4 (95% CI, 1.0-5.8) for dome/neck ratio, and 2.0 (95% CI, 0.6-7.0) for location in the posterior circulation. CONCLUSIONS: Initial aneurysm size, dome/neck ratio, and multilobarity are risk factors for aneurysm growth. Cessation of smoking is pivotal because smoking is a modifiable risk factor for growth of small aneurysms.

PHASES Score for Prediction of Intracranial Aneurysm Growth.

BACKGROUND AND PURPOSE: Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth. METHODS: In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles. RESULTS: We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5-10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22-1.43). With the lowest quartile of the PHASES score (0-1) as reference, hazard ratios were for the second (PHASES 2-3) 1.07 (95% CI, 0.49-2.32), the third (PHASES 4) 2.29 (95% CI, 1.05-4.95), and the fourth quartile (PHASES 5-14) 2.85 (95% CI, 1.43-5.67). CONCLUSIONS: Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.

Difference in aneurysm characteristics between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms.

BACKGROUND AND PURPOSE: Prediction of the risk of rupture of unruptured intracranial aneurysms is mainly based on aneurysm size and location. Previous studies identified features of aneurysm shape and flow angles as additional risk factors for aneurysm rupture, but these studies were at risk for confounding by patient-specific risk factors such as hypertension and age. In this study, we avoided this risk by comparing characteristics of ruptured and unruptured aneurysms in patients with both aneurysmal subarachnoid hemorrhage and multiple intracranial aneurysms. METHODS: We included patients with aneurysmal subarachnoid hemorrhage and multiple aneurysms who presented to our hospital between 2003 and 2013. We identified the ruptured aneurysm based on bleeding pattern on head computed tomography or surgical findings. Aneurysm characteristics (size, location, shape, aspect ratio [neck-to-dome length/neck-width], flow angles, sidewall or bifurcation type, and contact with bone) were evaluated on computed tomographic angiograms. We calculated odds ratios with 95% confidence intervals with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size and location. RESULTS: The largest aneurysm had not ruptured in 36 (29%) of the 124 included patients with 302 aneurysms. Odds ratios for aspect ratio≥1.3 was 3.3 (95% confidence intervals [1.3-8.4]) and odds ratios for irregular shape was 3.0 (95% confidence intervals [1.0-8.8]), both after adjustment for aneurysm size and location. CONCLUSIONS: Aspect ratio≥1.3 and irregular shape are associated with aneurysm rupture independent of aneurysm size and location, and independent of patient characteristics. Additional studies need to assess to what extent these factors increase the risks of rupture of small aneurysms in absolute terms.

Anosmia after coiling of ruptured aneurysms: prevalence, prognosis, and risk factors.

BACKGROUND AND PURPOSE: Anosmia occurs frequently in patients with subarachnoid hemorrhage (SAH) from a ruptured aneurysm treated with clipping. We analyzed prevalence, prognosis, and potential risk factors for anosmia after coiling for SAH. METHODS: We interviewed all patients who resumed independent living after SAH treated with coiling between 1997 and 2007. We assessed by means of logistic regression analyses whether risk of anosmia was influenced by site of the ruptured aneurysm, neurological condition on admission, amount of extravasated blood, hydrocephalus, and treatment for hydrocephalus. RESULTS: Of 197 patients, 35 (18%; 95%CI:12 to 23) experienced anosmia. Anosmia had improved in 23 (66%) of them; in 20 the recovery had been complete after a median period of 6 weeks (SD +/-6.5). Intraventricular hemorrhage was a risk factor for anosmia (OR 2.4; 95%CI:1.0 to 5.9). Anterior aneurysm location (OR 1.1; 95%CI:0.5 to 2.3) and high amount of extravasated blood (OR 0.9; 95%CI:0.4 to 2.1) were not related to anosmia. CONCLUSIONS: Anosmia occurs after coiling in 1 of every 6 SAH patients, but has a good prognosis in most patients. The cause of anosmia after coiling for ruptured aneurysms remains elusive; severity of the initial hemorrhage or long lasting hydrocephalus may be contributing factors.

Long-term, serial screening for intracranial aneurysms in individuals with a family history of aneurysmal subarachnoid haemorrhage: a cohort study.

BACKGROUND: Individuals with two or more first-degree relatives who have had aneurysmal subarachnoid haemorrhage (aSAH) have an increased risk of aneurysms and aSAH. We investigated the yield of long-term serial screening for intracranial aneurysms in these individuals. METHODS: In a cohort study, we reviewed the results of screening of individuals with a positive family history of aSAH (two or more first-degree relatives who had had aSAH or unruptured intracranial aneurysms) done at the University Medical Centre Utrecht (Utrecht, Netherlands) between April 1, 1993, and April 1, 2013. Magnetic resonance angiography or CT angiography was done from age 16-18 years to 65-70 years. After a negative screen, we advised individuals to contact us after 5 years, but did not actively call them for repeated screening. We recorded familial history of ruptured and unruptured intracranial aneurysms, smoking history, hypertension, previous aneurysms, screening dates, and screening results. We identified risk factors for positive initial and follow-up screens with univariable and multivariable regression analysis. FINDINGS: We identified aneurysms in 51 (11%, 95% CI 9-14) of 458 individuals at first screening, in 21 (8%, 5-12) of 261 at second screening, in seven (5%, 2-11) of 128 at third screening, and three (5%, 1-14) of 63 at fourth screening. Five (3%, 95% CI 1-6) of 188 individuals without a history of aneurysms and with two negative screens had a de-novo aneurysm in a follow-up screen. Smoking (odds ratio 2·7, 95% CI 1·2-5·9), history of previous aneurysms (3·9, 1·2-12·7), and familial history of aneurysms (3·5, 1·6-8·1) were significant risk factors for aneurysms at first screening in the multivariable analysis. History of previous aneurysms was the only significant risk factor for aneurysms at follow-up screening (hazard ratio 4·5, 1·1-18·7). Aneurysms were identified in six (5%, 95% CI 2-10) of 129 individuals who were screened before age 30 years. One patient developed a de-novo aneurysm that ruptured 3 years after the last negative screen. INTERPRETATION: In individuals with a family history of aSAH, the yield of long-term screening is substantial even after more than 10 years of follow-up and two initial negative screens. We advocate long-term serial screening in these individuals, although the risk of aSAH within screening intervals is not eliminated. FUNDING: The Dutch Heart Foundation.

Optimal screening strategy for familial intracranial aneurysms: a cost-effectiveness analysis.

OBJECTIVE: Individuals with a family history of subarachnoid hemorrhage (SAH), defined as 2 or more affected first-degree relatives, have an increased risk of aneurysm formation and rupture. Screening such individuals for intracranial aneurysms is advocated, but its effectiveness and cost-effectiveness are unknown, as are the optimal age ranges and interval for screening. METHODS: With a Markov model and Monte Carlo simulations we compared screening with no screening in individuals with a family history of SAH. We varied age ranges (starting screening at 20, 30, or 40 years old, ending screening at 60, 70, or 80 years old) and screening intervals (2-, 3-, 5-, 7-, 10-, and 15-year interval), and analyzed the impact in costs and quality-adjusted life years (QALY). RESULTS: Screening individuals with a family history of SAH is cost-effective. The strategy with the lowest costs per QALY was to screen only twice, at 40 and 55 years old. Sequentially lengthening the screening period and decreasing the screening interval yielded additional health benefits at acceptable costs up to screening from age 20 to 80 every 7 years. More frequent screening within this age range still provided extra QALYs, with an incremental cost-effectiveness ratio more favorable than 26,308/QALY ($38,410/QALY). CONCLUSION: This study provides evidence for recommendations to screen individuals with 2 or more first-degree relatives with subarachnoid hemorrhage. The optimal screening strategy according to our model is screening from age 20 until 80 every 7 years given a cost-effectiveness threshold of 20,000/quality-adjusted life year (QALY) ($29,200/QALY).

Configuration of intracranial arteries and development of aneurysms: a follow-up study.

BACKGROUND: The reasons for development of intracranial aneurysms are unknown; hemodynamic factors may play an important role in this process. We performed a cohort study to further elicit the role of intracranial arterial geometry. METHODS: We compared the original CTA/MRA of the circle of Willis of 26 patients who developed an aneurysm during follow-up with those of 78 controls with no aneurysm development who were matched for gender, age, and period of follow-up. We assessed hypoplasia of the arteries of the circle of Willis and measured bifurcation angles within and beyond the circle of Willis on three-dimensional CTA/MRA. Bifurcation angles were classified in tertiles for analysis. We used Student t test for comparison of bifurcation angles and calculated OR with corresponding 95% CI for presence of hypoplasia and bifurcation angles in tertiles. RESULTS: A hypoplastic branch was found in 5 of 7 (71%) sites with aneurysm development and in 6 of 21 corresponding sites (29%) without aneurysm development (OR 6; 95%CI 0.9 to 42). The branch angle was sharp (lowest tertile) in 10 of 14 (71%) sites with aneurysm development and in 8 of 42 (19%) sites without aneurysm development (OR 11.3; 95% CI 2.0 to 64). CONCLUSIONS: Bifurcations with a hypoplastic branch and bifurcations with sharper bifurcation angles are risk factors for development of aneurysms. Analysis of the geometry of intracranial arteries might be helpful in detecting persons with increased risk for developing aneurysms.