Screening for Intracranial Aneurysm in 355 Patients With Autosomal-Dominant Polycystic Kidney Disease
Background and Purpose—The association of autosomal-dominant polycystic kidney disease (ADPKD) with intracranial aneurysm (ICAN) is well known but little is known about the characteristics of ICAN in ADPKD. The purpose of this study was to investigate the prevalence and characteristics of ICAN in ADPKD.
Methods—We screened 355 patients with ADPKD (mean age, 46.5±13.2 years; range, 7 to 87 years) with 3-dimensional time-of-flight MR angiography. Size, location, and morphology of aneurysms were assessed. The prevalence and characteristics of ICAN in patients with ADPKD were evaluated. Patients with ICAN found by MR angiography and moderate renal function subsequently were recommended to undergo digital subtraction angiography for comparison.
Results—The prevalence of ICAN in ADPKD was 12.4% (95% CI, 8.95% to 15.82%) with an equal gender distribution. The prevalence increased as age increased, reaching a peak value of 23.3% (95% CI, 16.85 to 29.75%) in the 60- to 69-year age group. The prevalence of ICAN in patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN was higher than patients with ADPKD lacking such family history (relative risk, 1.968; 95% CI, 1.57 to 2.67). The mean diameter of ICAN was 3.85±3.25 mm. The most frequent site of ICAN was the internal carotid artery. The result of digital subtraction angiography of 15 patients with 18 ICANs and moderate renal function corresponded to the detection of MR angiography.
Conclusion—The characteristics of ICAN in patients with ADPKD were different from some previous reports. Systematic screening of ICAN with 3-dimensional time-of-flight MR angiography is recommended for patients with ADPKD, particularly for adult patients (≧30 years) or patients with a positive family history of hemorrhagic stroke or ICAN.
Autosomal-dominant polycystic kidney disease (ADPKD) is 1 of the most common single-gene hereditary disorders, which is a systemic disorder associated with various extrarenal manifestations such as hypertension, hepatic cysts, and intracranial aneurysms (ICANs).1 Compared with the general population, patients with ADPKD have an increased frequency of ICAN with estimates of prevalence ranging from 4% to 41% and the morbidity of aneurysmal subarachnoid hemorrhage is higher in patients with ADPKD with half of those who survive having severe neurological deficits.2,3 Therefore, screening of patients with ADPKD for ICAN is an important issue. In this study, we screened for ICAN in 355 patients with ADPKD with 3-dimensional time-of-flight MR angiography at 3 T. To our knowledge, this is the largest study of ICAN in association with ADPKD to date.
Materials and Methods
This retrospective study was approved by ethics committees at both Shang Hai Jiao Tong University and the Second Military Medical University of China. Informed consent was obtained from each subject participating in this study.
During the period from November 1, 2007, to November 20, 2008, a total of 378 consecutively diagnosed patients with ADPKD from the department of nephrology in Chang Zheng Hospital affiliated with the Second Military Medical University of China were invited to participate in this study. The diagnosis of ADPKD was made on the basis of abdominal ultrasound or CT examination that showed ≥5 cysts in both kidneys, usually in addition to a family history of polycystic kidney disease.
Twenty-three patients refused to participate in this study, and the remainder (355 patients, response rate of 93.9%) underwent 3-dimensional time-of-flight MR angiography at 3 T free of charge. Patients with ICAN found by MR angiography and moderate renal function (serum creatinine <4 mg/dL) were recommended for digital subtraction angiography (DSA) as a reference standard for comparison. If MR angiography revealed negative results, no DSA was performed.
These 355 patients with ADPKD (169 women, 186 men) came from 288 families with a mean age of 46.5±13.2 years (range, 7 to 87 years). Detailed information is shown in Table 1.
MR Angiography and DSA
All MR angiographies were performed on a 3-T system (Achieva; Philips Medical Systems) and DSA including conventional intra-arterial DSA, rotational DSA, and 3-dimensional reconstruction.
The primary analysis of this study is the estimation of the frequency of ICAN detected in patients with ADPKD. The frequency was estimated and a 95% CI constructed for the estimate. Other data were expressed as mean±SD and processed with the statistical software SPSS 15.0 (SPSS Inc). Quantitative and qualitative data were analyzed with variance analysis and the χ2 test, respectively. Logistic regression was used to analyze the factors. P<0.05 was considered statistically significant.
One fusiform and 53 saccular aneurysms were detected in 44 patients (52.6±10.6 years, 23 women and 21 men) from 38 families. The clinical data of patients with ADPKD with and without ICAN are shown in Table 1.
The prevalence of patients with ICAN among 355 patients with ADPKD was 12.4% (95% CI, 8.95% to 15.82%) and the prevalence in female patients (13.6%) was 1.2 times higher than in male patients (11.3%), but there were no statistically significant differences in gender distribution (P=0.528), indicating ICANs have an equal gender distribution in patients with ADPKD. If excluding those <30 years old (n=42), the prevalence of patients with ADPKD (≧30 years old) with ICAN increased to 13.7% (95% CI, 9.96% to 17.60%). The prevalence of ICAN in patients with ADPKD increased with age increasing, reaching a peak value of 23.3% (95% CI, 16.85% to 29.75%) in the 60- to 69-year age group. All ICANs but 1 were small (<10 mm) with a mean diameter of 3.85±3.25 mm (range, 1.7 to 25 mm); 23 aneurysms (43.4%) were ≦3 mm; 25 aneurysms (47.2%) were 3 to 6 mm; 4 aneurysms (7.5%) were 6 to 10 mm; and 1 aneurysm (1.9%, 25 mm) was >10 mm. All ICANs were located in the anterior circulation (26 at the internal carotid artery, 14 at the middle cerebral artery, 13 at the anterior communicating artery, and 1 at the anterior cerebral artery). A single aneurysm was detected in 36 patients (81.8%), whereas multiple aneurysms were detected in 8 patients (18.2%). The characteristics of the aneurysms are shown in Tables 2 and 3.
ICANs have a higher prevalence of 21.6% in patients with a positive family history of hemorrhagic stroke or ICAN compared with 8.3% in patients with a family history of possible hemorrhagic stroke or ICAN and 11.0% in patients with a negative family history of hemorrhagic stroke or ICAN (relative risk, 1.968).
No statistically significant differences in ICAN prevalence were found based on hypertension (P=0.722); moreover, the prevalence of ICAN in patients with ADPKD was unrelated to renal function (P=0.302), liver cysts (P=0.517), and duration of ADPKD (P=0.141), but it was correlated with duration of hypertension (P=0.001). The size of aneurysms was also unrelated to age of the patient (P=0.127).
Fifteen patients with 18 ICANs detected by MR angiography subsequently volunteered to undergo DSA, which showed all 18 aneurysms. No additional aneurysms were found by DSA.
Although the high incidence of ICAN in patients with ADPKD has long been recognized, the exact frequency of the association is unclear, and little is known about the specific characteristics of ICAN in patients with ADPKD.
In our study, we found a prevalence of 12.4% for ICAN in patients with ADPKD, which is a slightly higher than reports of Huston and Ruggieri (10% and 11.7%, respectively).4,5 In addition, the incidence of ICAN in patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN was higher versus patients with ADPKD lacking such a family history. Thus, for patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN, systematic screening is strongly recommended.
The characteristics of ICAN differ in other respects between our study and some of the previous literature. In most studies, the frequent site of aneurysm was different between patients with ADPKD and the general population. The most frequently reported site of aneurysm in patients with ADPKD is the middle cerebral artery, and almost 5% to 10% aneurysms are located in the posterior circulation; large aneurysms seem to occur more frequently in patients with ADPKD in that the proportion of large aneurysms (>10 mm) was 27%. In the general population, however, the most frequent site of aneurysms is the internal carotid artery; in large aneurysms, it is <7%.6,7 In our study, however, ICANs were most frequently located in the internal carotid artery, which accounted for nearly half of the overall ICANs. No ICANs were detected in the posterior circulation, which may be a beneficial message. In general, ICANs in the posterior circulation have a higher risk of rupture than that in the anterior circulation.8 We think these differences may be attributed to racial and ethnic differences, although there have not been reports with regard to the Asian population to confirm or oppose our results.
- Received January 31, 2010.
- Revision received September 13, 2010.
- Accepted September 15, 2010.
- © 2010 American Heart Association, Inc.
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