Value of Magnetic Resonance Angiography for the Detection of Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease1 2

Transcription

1 Value of Magnetic Resonance Angiography for the Detection of Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease 2 John Huston III, Vicente E. Torres, Patrick P. Sulivan, Kenneth P. Offord, and David 0. Wiebers J. Huston, P.P. Sullivan, Department of Diagnostic Radiology. Mayo Clinic and Mayo Foundation. Rochester, MN ye. Torres, Division of Nephrology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN K.P. Offord, Section of Biostatistics, Mayo Clinic and Mayo Foundation. Rochester, MN DO. Wiebers, Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester. MN (J. Am. Soc. Nephrol. 993; 3:87-877) ABSTRACT The association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD), the 30-day mortality rate exceeding 50% for aneurysmal rupture, the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk, and the development of noninvasive imaging techniques for their detection have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. The sensitivity and specificity of high-resolution computed tomography and magnetic resonance imaging for the diagnosis of small intracranial aneurysms have been disappointing. To determine the value of magnetic resonance angiography (MRA), 85 patients with ADPKD without symptoms related to an intracranial aneurysm and 2 patients with ADPKD presenting with a subarachnoid hemorrhage or a suspected aneurysmal leak were studied. MRA was performed with the Multisequence Vascular Package (GE Medical Systems) with use of three-dimensional time-of-flight and three-dimensional phase-contrast techniques, and postprocessing maximum intensity projection im- I Received December 9, 992. Accepted March Presented In part at the 25th Annual Meeting of the American Society of Nephrology. Baltimore, MD. November 5 to Correspondence to Dr. J Huston, Department of Diagnostic Radiology, Mayo Clinic, 200 FIrst Street SW, Rochester, MN / /0 Journal of the American Society of Nephrology Copyright 993 by the American Society of Nephrology ages were generated to eliminate the problem of overlapping vessels. Asymptomatic intracranial aneurysms were detected in 6 (22%) of 27 patients with and 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02, information missing in 2 patients) and in the 2 patients who presented with a symptomatic aneurysm. A stepwise logistic regression analysis indicated that a family history of intracranial aneurysm or subarachnoid hemorrhage was independently associated with the presence of intracranial aneurysms. All of the aneurysms were s6.5 mm in diameter. These observations, together with previous experience with high-resolution computed tomography and magnetic resonance imaging, suggest that MRA is superior to computed tomography and magnetic resonance imaging in the presymptomatic detection of intracranial aneurysms and confirm a familial clustering of intracranial aneurysms in ADPKD. Key Words; Aneurysm. autosomal dominantpo/ycystic kidney disease. magnetic resonance angiography. subarachnoid hemorrhage T he association of intracranial aneurysms with autosomal dominant polycystic kidney disease (ADPKD) ( -4) combined with a 30-day mortality rate exceeding 50% after aneurysmal rupture (5) and the effectiveness of surgical repair of unruptured aneurysms with a low surgical risk (6-8) have led physicians to consider the value of screening patients with ADPKD for unruptured intracranial aneurysms. A decision analysis has not supported the routine use of cerebral arteriography (9). With the development of high-resolution computed tomography (CT) and magnetic resonance, noninvasive visualization of intracranial aneurysms has become possible ( 0, ). Although the sensitivity of high-resolution CT and magnetic resonance Imaging to detect large intracranial aneurysms appears to be adequate, the specificity of these techniques to diagnose small intracranial aneurysms has been low ( 0, ). The purpose of this study was to determine the value of magnetic resonance angiography (MRA) in the presymptomatic diagnosis of intracranial aneurysms in patients with ADPKD. Journal of the American Society of Nephrology 87

2 MPA Detection of Intracranial Aneurysms in ADPKD MATERIAL AND METHODS Patients The patients with ADPKD seen by the authors during the period from 989 to 992 were given detailed information regarding the association of intracranlal aneurysms and ADPKD and the possible indications for noninvasive presymptomatic evaluatlon for Intracranial aneurysms in this disease. This information was based in part on the results of our previous studies ( 0. 2). Eighty-five asymptomatic ADPKD patients from 80 families agreed to undergo MRA. Indications included a family history of intracranial aneurysms (N = 26), evaluation before major elective surgery or renal transplantation (N = 3), or request by the patient for the purpose of reassurance (N = 28). One patient evaluated before renal transplantation was later classified as having a positive family history when, as part of the study, her son was discovered to have an intracranial aneurysm. In addition, two symptomatic patients with histories of subarachnoid hemorrhage or suspected aneurysmal leak were studied during the same period. Information abstracted for the study included gender, age. presence of hypertension defined as a diastolic blood pressure 95 mm Hg or treatment with antihypertensive medications, serum creatinine level at the time of MRA, and family history of intracranial aneurysm or subarachnoid hemorrhage as diagnosed by a neurologist or a pathologist at our center or elsewhere. Eighty of the 87 patients had computed tomographies of the abdomen available for review. The severity of the polycystic liver disease was graded according to the extent of the cross-sectional area occupied by cysts as follows: mild, <0%; moderate, 0 to 40%, and severe, >40%. r;\. r A. I f / C-- Tl/ -J * us..,.- A. i:i Figure. MIP image through the entire data set with overlapping vessels partially obscuring vascular detail (a). 3D image with the right carotid subvolume outlined (b). Right carotid subvolume isolated from other vascular structures (c). Nine of 9 projection images of the right carotid subvolume allow enhanced perception of the carotid siphon aneurysm (arrow in panel d). 872 Volume 3 Number 2 993

3 Huston et al Methods Patients were examined with a.5-t superconducting imaging system (Signa; GI Medical Systems, Milwaukee, WI). Standard magnetic resonance head imaging was performed with sagittal T -weighted and transaxial T2-weighted sequences. In addition, high-resolution 3-mm transaxial Ti -weighted imag- Ing through the circle of Willis was performed. Vascular magnetic resonance imaging was performed with the Multisequence Vascular Package (GE Medical Systems, Milwaukee, WI) with the use of threedimensional (3D) time-of-flight (TF) (3,4) and 3D phase-contrast (PC) ( 5, 6) techniques. A coronal 2D PC scout image with 30 cm/s maximum velocity encoding was obtained to localize the volume for 3D TF and 3D PC imaging. Then, 3D PC angiography was performed in all patients (TR, 26 to 36; TE, 7.4 to 8.2, one excitation, 28 views, 5- to 20-degree flip angle, 8-cm field of view, 30 cm/s maximum velocity encoding) with the use of 60 axial sections between 0.7 and.0 mm thick. Additionally. 3D TF imaging was performed in 5 patients (TR, 40; TE, 4.3 to 6.0; one excitation, 92 to 256 views, 20-degree flip angle, 8-cm field of view) with the use of 60 axial sections between 0.7 and.0 mm thick. With both the 3D TF and 3D PC sequences, postprocesslng maximum intensity projection (MIP) images were generated to eliminate the problem of overlapping vessels (Fig. ) (i7). This resulted in i9 MIP images perpendicular to the axial imaging plane at 0-degree increments. These subvolumes were selected from the MIP image along the axial imaging plane of both the 3D TF and the 3D PC series. Care was taken to include the anterior communicating artery in both carotid volumes. Viewing the individual subvolumes in a cine loop on an independent monitor enhanced the perception of the 3D relationship of the vessels and facilitated the identification of small aneurysms (Fig. 2). Statistical Analysis Two sample t tests, x2 and Mantel-Haenszel x2 analyses were used for comparisons between the groups of patients with and without intracranial aneurysms. In addition, a stepwise logistic regression analysis with backward elimination of variables that did not achieve a P = 0.05 level of significance was used to assess the predictive value of age. gender, family history of intracranial aneurysm or subarachnoid hemorrhage, history of hypertension, serum creatinine level, and severity of the polycystic liver disease on the presence of intracranial aneurysms detected by MRA (i 8). These analyses were done both including and excluding the two patients with ADPKD and symptomatic intracranial aneurysms. Only two-tailed P values are reported. Figure 2. Careful attention to postprocessing is required for accurate image interpretation. Early in our experience, only two subvolumes were obtained to separate the carotid circulation (a) from the posterior circulation. With improved postprocessing software, optimal window and level image parameters, and separate right and left carotid systems, this right MCA bifurcation aneurysm is clearly seen by both PC (arrow in panel b) and TF (arrow in panel c) techniques. The aneurysm was not identified by the original postprocessing technique (arrow in panel a). RESULTS Intracranial aneurysms, one in each of patients, were detected in 9 asymptomatic patients with ADPKD (Figs. i through 3) and in the 2 patients with ADPKD who presented with symptoms related to an aneurysmal rupture or suspected aneurysmal leak (Fig. 4). Multiple aneurysms were not detected in any of these patients. The latter two patients underwent conventional angiography and surgical clipping of the aneurysms without complications. The gender and age of the patients with intracranial aneurysms and the location and size of the aneurysms are summarized in Table. All of the aneurysms were s6.5 mm in maximal diameter. The clinical data on the patients with ADPKD with and without intracranial aneurysms are shown in Table 2. A family history of intracranial aneurysms Journal of the American Society of Nephrology 873

4 MRA Detection of Intracranial Aneurysms in ADPKD A: 4I4f - B.% i..,w ls I I j..., ).-,* i -_..u.. \I #{49} I \.. \ \. Figure 3. High-resolution 52 x 256 3D TF imaging is superior to 3D PC imaging for detecting small intracranial aneurysms. Forty-five-year-old woman with a.5-mm right superior cerebellar artery aneurysm identified with 52 x 256 3D TF imaging (arrow in panel a) that was not apparent on 3D PC imaging (arrow in panel b)., ( Figure 4. Forty-nine-year-old woman with a sudden onset of a severe headache. MRA identified a 5-mm right MCA bifurcation aneurysm (arrow in panel a). This finding was confirmed by conventional angiography (arrow in panel b) and at surgery when clipping of the aneurysm was performed. or subarachnoid hemorrhage and the presence of severe polycystic liver disease were associated with the presence of intracranial aneurysms detected by MRA. A stepwise logistic regression analysis with backward elimination of nonsignificant variables indicated that both the family history of intracranial aneurysm or subarachnoid hemorrhage and the presence of severe polycystic liver disease were Independently associated with the presence of Intracranial aneurysms (Table 3). Both patients with symptomatic intracranial aneurysms had severe polycystic liver disease, but neither one had a family history of intracranial aneurysm or subarachnold hemorrhage. Excluding these two patients from the analysis. the univarlate association between family history and presence of aneurysms continues to be significant (P = 0.0), whereas the association with severe polycystic liver disease is not (P = 0.23). Thus, the I 874 Volume 3 Number 2 993

5 Huston et al presence of severe polycystic liver disease was not a significant predictor for the presence of an intracranial aneurysm in asymptomatic patients. Asymptomatic intracranial aneurysms were detected by MRA in 6 (22%) of 27 patients with and in 3 (5%) of 56 patients without a family history of intracranial aneurysm or subarachnoid hemorrhage (P = 0.02 ). Other vascular abnormalities noted in these patients included an ectatic middle cerebral artery in TABLE I. Location and size of I I intracranial aneurysms detected by MRA in nine asymptomatic and two symptomatic ADPKD patients Location Size#{76} (mm) AP SI RL Figure Asymptomatic 58Fb Rt carotid siphon F Lt periophthalmic SF Basilar tip I.5 47F Rt MCA bifurcation SF Rt superior cerebellar I F Rt carotid siphon M Lt carotid siphon F Lt carotid siphon M Rt MCA bifurcation I I.5 Symptomatic 49F Rt MCA bifurcation M Lt anterior cerebral AP. anteroposterior; SI. superior-inferior; RL, right-left. b Age (years) and sex of patient. one patient, fetal origin of a posterior cerebral artery in two patients, hypoplastic cerebral arteries in two patients, and absence of a lateral sinus in one patient. Additional findings included an arachnoid cyst in five patients, cavum septum pellucidum in two, pineal cyst in one, and empty sella in one. DISCUSSION Intracranial aneurysms were detected by MRA in 9 ( i %) of 85 patients with ADPKD who had no symptoms related to the presence of aneurysms. Because of numerous referral and selection biases, this frequency should be viewed as only an approximation of the frequency of intracranial aneurysms in this disease. Similar biases have influenced previous autopsy and angiography studies and have resulted In highly variable frequencies ranging from 0 to 50% at autopsy ( -4, i 2, i 9) and from 8 to 60% in studies using conventional arteriography (,20-24). The most recent and comprehensive studies of this association suggest that the overall prevalence of intracranial aneurysms in ADPKD does not exceed 0% (, 2), which is in agreement with the findings of this study. With the development of high-resolution CT and magnetic resonance imaging, the noninvasive visualization of intracranial aneurysms became possible ( 0, i). Although these imaging techniques have sensitivity adequate enough to detect large intracranial aneurysms, their specificity for the detection of small aneurysms has been disappointing. In our previous study of 96 patients with ADPKD, small areas (2 to 4 mm) of contrast enhancement or signal void, TABLE 2. Clinical data on the patients with ADPKD with and without ICA at the time of MRA#{76} With ICA (N= ) Without ICA (N =76) PValue Age(yr) 48± (29-72) 45± 2(7-67) NS Sex(M:F) 3:8 3:45 NS Family history of ICAb 6/ (55%) 2/74 (28%) 0.08 Hypertension 0/ (9%) 66/76 (87%) NS Serum Creatinine (mg/dl).2 2(8%) 28(34%) (46%) 27(32%) (27%) 3 (8%) ESRF I (9%) 8 (0%) NS Polycystic liver diseasec None I (0%) 4(20%) Mild (<0% SA) 2 (20%) 26 (38%) Moderate (0-40% SA) 2 (20%) 6 (23%) Severe (>40% SA) 5 (50%) 3 (9%) CA. intracranial aneurysm; ESRF, end-stage renal failure; SA. cross-sectional area on CT; NS. not significant. b Information not available in two patients without ICA. C Information not available in seven patients without and one patient with ICA. Journal of the American Society of Nephrology 875

6 MRA Detection of Intracranial Aneurysms in ADPKD TABLE 3. Frequency of intracranial aneurysms according to family history of intracranial aneurysms and severity of polycystic liver diseasea Family History of Aneu- Degree of Liver In- N rysmsb volvement - - No Yes None Mild Moderate Severe Missing Total None Mild Moderate Severe Missing Total (4) 5 56(58) (3) 3(5) Ane urysm Present (2.4) (8.6) a Numbers in parentheses include the two patients with symptomatic aneurysms. U Information not available in two patients. possibly due to vascular tortuosity or small aneurysms, were noted in patients but no definite aneurysms were detected (io). Two of these patients subsequently underwent conventional arteriography, which failed to detect any aneurysms. Similarly, Chapman et at. detected areas suspicious for intracranial aneurysms in of 69 patients with ADPKD who had high-resoltuion CT. Seven of these patients underwent conventional arteriography, and Intracranial aneurysms were found in only 2 patients ( ). Thus. high-resolution CT or magnetic resonance Imaging detected definite intracranial aneurysms in only 2 of the 65 patients in these combined series. By comparison, MRA in this study detected definite aneurysms in 9 of 85 patients who had no symptoms related to the presence of aneurysms (P < 0.00). In addition, MRA also detected definite aneurysms, subsequently confirmed by conventional arteriography, in two symptomatic patients. These results suggest that MRA is superior to high-resolution CT and magnetic resonance imaging for the detection of small intracranial aneurysms. The improvement in the postprocessing software that has occurred in the last 2 yr allows viewing of mdividual volumes in a clne loop, enhancing the perception of the 3D relationship of the vessels and facilitating the Identification and accurate measurement of very tiny aneurysms and their distinction from other vascular structures. In addition, because no Intravascular contrast medium is required. MRA is suitable for ADPKD patients who have impaired renal function. Several investigators have suggested that patients with ADPKD and a family history of intracranial aneurysm or subarachnoid hemorrhage are more likely to have an intracranial aneurysm (25-27). The results of our study are consistent with these observatlons. Intracranial aneurysms were detected in 5% of our patients without and in 22% of our patients with a family history of intracranial aneurysm or subarachnoid hemorrhage. Our study also suggests a possible association between the severity of the polycystic liver disease and the presence of an intracranial aneurysm. This association, however, only reaches statistical significance when two patients with symptomatic intracranial aneurysms detected by MRA are included in the analysis. This observatlon, along with the report by Chauveau et al. of intracranial aneurysms in two patients with severe polycystic kidney disease and renal failure at an early age (28), may suggest an increased risk for the presence of aneurysms in patients with a severe expresslon of polycystic kidney or liver disease. Age, gender, history of hypertension. and renal function were not found to be significant predictors for the presence of an aneurysm. The value of presymptomatic detection of intracranial aneurysms by MRA in patients with polycystic kidney disease is dependent upon the natural history of unruptured intracranial aneurysms and the risk! benefit ratio of interventional therapy. In the general population, aneurysmal size is an important variable for predicting the future rupture of unruptured Intracranial aneurysms in the absence of prior subarachnoid hemorrhage from a different source (29,30). For unruptured aneurysms less than i 0 mm in diameter in patients with no prior subarachnoid hemorrhage, the risk of subsequent rupture appears to be low. Whether this is also true in patients with ADPKD is uncertain, because it has been suggested that familial intracranial aneurysms in general rupture at a smaller size and when the patient is younger in comparison with sporadic intracranial aneurysms (3). In addition, several studies have suggested that intracranial aneurysms in ADPKD rupture with the patients at a younger age than do intracranial aneurysms in the general population (2,32.33). ACKNOWLEDGMENTS Research supported by grant DK44863 from the NIH. REFERENCES. Suter W: Das kongenitale aneurysma der basalen gehinarterien und cystennleren. Schweiz Med Wochenschr 949;79:47i Brown RAP: Polycystic disease of the kidneys and intracranial aneurysms: The etiology and interrelationship of these conditions: Review of recent literature and report of seven cases in 876 Volume 3 Number 2 993

7 Huston et al which both conditions coexisted. Glasg Med J 95:32: Bigelow NH: The association of polycystic kidneys with intracranial aneurysms and other related disorders. Am J Med Sd 953:225: Torres VE, Holley KE, Offord KP. Epidemiology. In: Grantham JJ, Gardner KD, eds. Problems in Diagnosis and Management of Polycystic Kidney Disease, Proceedings of the First International Workshop. Kansas City: PKR Foundation; 985: Iglesias CG, Torres VE, Offord KP, Holley KE, Beard CM, Kurland LT: Epidemiology of adult polycystic kidney disease, Olmsted County. Mmnesota: Am J Kidney Dis 983:2: Wirth FP, Laws ER Jr, Piepgras D, Scott RM: Surgical treatment of incidental intracranial aneurysms. Neurosurgery 983; i 2:507-5 i. 7. Rice BJ, Peerless SJ, Drake CG: Surgical treatment of unruptured aneurysms of the posterior circulation. J Neurosurg 990:73: i Nishimoto A, Ueta K, Onbe H, et at. : Nationwide co-operative study of intracranial aneurysm surgery in Japan. Stroke 985;6: Levey AS, Pauker 5G. Kassirer JP: Occult intracranial aneurysms in polycystic kidney disease: When is cerebral arteriography indicated? N Engl J Med 983;308: Torres VE, Wiebers DO, Forbes GS: Cranial computed tomography and magnetic resonance imaging in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 990; : Chapman AB, Rubinstein D, Hughes R, et at.: Intracranial aneurysms in autosomal dominant polycystic kidney disease. N Engl J Med 992; 327: Schievink WI, Torres VE, Piepgras DG, Wiebers DO: Saccular intracranial aneurysms in autosomal dominant polycystlc kidney disease. J Am Soc Nephrol i992;3: Ruggien PM, Gerhard AU, Masaryk TJ, Modic MT: Intracranial circulation : Pulse-sequence considerations in three-dimensional (volume) MR angiography. Radiology 989; 7: Keller PJ, Drayer BP, Pram EK, et at.: MR angiography with two-dimensional acquisition and three-dimensional display. Radiology 989; 73: Dumoulin CU, Hart HR: Magnetic resonance anglography. Radiology 986;6 : Dumoulin CL, Souza SP, Walker MF, Wagle W: Three-dimensional phase contrast angiography. Magn Reson Med 989;9: Huston J, Rufenacht DA, Ehman RU, Wiebers DO: Intracranial aneurysms and vascular malformations: Comparisons of time-of-flight and phase-contrast MR angiography. Radiology 99i;8:72i Heiwig JT, Council KA (eds): Statistical Analysis System User s Guide. Cary, NC: SAS Institute; Lazarus JM, Bailey GU, Hampers CL, et at.: Hemodialysis and transplantation in adults with polycystic renal disease. JAMA i 97 :27: Ishibashi A: Renal imagings in the diagnosis of polycystic kidney disease. Jpn J Nephrol 98: 23: Wakabayashi T, Fujita S. Ohbora Y, Suyama T, Tamaki N, Matsumoto 5: Polycystic kidney disease and intracranial aneurysms. Early anglographic diagnosis and early operations for the unruptured aneurysm. J Neurosurg 983;58: Matsumura M, Wada H, Nojiri K, Ohwada A, Shinoda T: Unruptured intracranial aneurysms In polycystic kidney disease. Acta Neurochir 986:70: Tapaninaho A, Ryynanen M, Vapahlati M, et at. : Polycystic kidney disease and intracranial aneurysms [Abstract]. Acta Neurochir 989;98: Higashihara E, Aso Y, Shimazaki J, Ito H, Koiso K, Sakai 0: Clinical aspects of polycystic kidney disease. J Urol 992;47: Kaehny W, Bell P. Earnest M, Stears J, Gabow P: Family clustering of intracranial aneurysms (ICA) in autosomal dominant polycystic kidney disease (ADPKD) [Abstract]. Kidney Int 987; 3: Saifuddin A, Dathan JRE: Adult polycystic kidney disease and intracranial aneurysms. BMJ 987:295: Fehlings MG, Gentili F: The association between polycystic kidney disease and cerebral aneurysms. Can J Neurol Sd 99:8: Chauveau D, Sirieix M-F, Schillinger F, Uegendre C, GrUnfeld J-P: Recurrent rupture of intracranial aneurysms in autosomal dominant polycystic kidney disease. BMJ 990:30: Wiebers DO, Whisnant JP, Sundt TM, O Fallon WM: The significance of unruptured intracranial saccular aneurysms. J Neurosurg 987:66: Wiebers DO, Tones VE: Screening for unruptured intracranial aneurysms in ADPKD. N Engl J Med i992;327: Lozano AM, Leblanc R: Familial intracranial aneurysms. J Neurosurg 987:66: Lozano AM, Leblanc R: Cerebral aneurysms and polycystic kidney disease: A critical review. Can J Neurol Sd 992:9: Chauveau D, Pirson Y, GrUnfeld JP: Intracranial aneurysms and autosomal-dominent polycystic kidney disease: Preliminary results of a cooperative study [Abstract]. Kidney Int 99; 39: 32. Journal of the American Society of Nephrology I 877