DÄ internationalArchive25/2008The Interdisciplinary Treatment of Unruptured Intracranial Aneurysms

Original article

The Interdisciplinary Treatment of Unruptured Intracranial Aneurysms

Dtsch Arztebl Int 2008; 105(25): 449-0. DOI: 10.3238/arztebl.2008.0449

Seifert, V; Gerlach, R; Raabe, A; Güresir, E; Beck, J; Szelényi, A; Setzer, M; Vatter, H; Rochemont, R D M d; Zanella, F; Sitzer, M; Berkefeld, J

Introduction: The purpose of this article is to present the results of microsurgical clipping or endovascular coil obliteration of unruptured intracranial aneurysms (UIA), in a single cerebrovascular center with regard to successful obliteration and periprocedural complications.
Methods: Data concerning patients with UIA were recorded in the neurovascular database of the neurosurgical department at the University of Frankfurt. The outcome of treatment was assessed with the modified Rankin Scale.
Results: 126 patients were treated by open surgery and 74 patients by endovascular coil obliteration. After treatment, the rate of new, mostly transient neurological deficits was 5%, and there were no deaths related to any treatment in this series. The outcome was good in 124 (98.4%) of the surgically treated patients and 73 (98.6%) of the endovascularly treated patients, and only 3 patients (1.5%) had a treatment-related unfavorable outcome. 98% of the treated aneurysms were satisfactorily obliterated. 7 endovascularly treated patients required retreatment because of coil compaction leading to recanalization of the aneurysm.
Conclusions: The majority of patients with unruptured intracranial aneurysms, even complex ones, can be treated by microsurgery or endovascular aneurysm obliteration with very good clinical results and a very low percentage of unfavorable outcomes. With careful patient selection and individualized assignment of the best form of treatment to each patient, we were able to achieve a low overall complication rate and a very high rate of obliteration in our specialized neurovascular center.
Dtsch Arztebl Int 2008; 105(25): 449–56
DOI: 10.3238/arztebl.2008.0449
Key words: unruptured intracranial aneurysm, clipping, coiling, complication, morbidity
LNSLNS The use of non-invasive neuroradiological techniques to evaluate non-specific symptoms is leading to an increase in incidental intracranial findings. Magnetic resonance imaging (MRI) screening showed 1.8% of the population to have unruptured intracranial aneurysms (UIA) (1), often diagnosed as an incidental finding. Deciding on the further procedure and the need for primary prophylaxis of subarachnoid bleeding is a challenge for all the disciplines involved in these patients' management. Treating UIA is only productive, however, if the expected morbidity risk associated with rupture relevantly exceeds the risk of treatment. The first important step is therefore to identify suitable patients. Available treatment modalities are microsurgical clipping and endovascular coil obliteration (e-table 1 gif ppt, e-table 2 gif ppt, e-table 3 gif ppt). The literature data, however, do not allow conclusions to be drawn as to whether either of these procedures is superior in principle. While views about which therapeutic approach is optimal are often controversial, the decision should be taken as a consensus agreement by the specialized disciplines involved in the patient's management. The purpose of this article was not to compare the two forms of treatment but to evaluate the results of the interdisciplinary treatment of a consecutive series of patients with unruptured aneurysms at a neurovascular center.

Methods
Since June 1999, all patients diagnosed with an intracranial aneurysm at the Neurocenter of Johann Wolfgang Goethe University in Frankfurt/Main, Germany (Department of Neurosurgery, Department of Neurology, and Institute for Neuroradiology) have been entered in the neurovascular database of the Department of Neurosurgery. The database includes both patients with subarachnoid bleeding (SAB) from a ruptured aneurysm and with UIA. Up to February 2007, altogether 1078 patients were entered in the database, of whom 790 suffered SAB from a ruptured aneurysm and were not analyzed further in this study. 288 patients (26.7%) had a total of 362 UIA. 200 (69.4%) of these patients received treatment. Reasons for conservative management in 88 patients (117 UIA) were either a very poor clinical state following SAB from another, ruptured aneurysm, small aneurysm size more suitable for follow-up observation, or the patient's wish not to be treated.

During follow-up, the number of UIA treated with both types of intervention at our center steadily increased (figure 1 gif ppt). Before establishing a treatment strategy, four-vessel digital subtraction angiography (DSA), including 3-D reconstruction was performed in each patient. No standard selection criteria were applied to decide the treatment modality, rather, every aneurysm was discussed jointly by an interdisciplinary team of experienced neurovascular neurosurgeons and neuroradiologists. The aneurysm criteria (size, morphology, configuration, site, relation to carrier vessel) as well as the patient criteria (age, life expectancy, comorbidity) and the patient's preference were the deciding factors for the type of treatment selected (table 1 gif ppt). There were no relevant differences between the two forms of treatment as regards the severity of existing comorbidities. When the optimal treatment had been selected in the interdisciplinary consultation, the result was discussed with the patient and the treatment with the anticipated lowest periprocedural risk and most stable longterm occlusion was presented as a definitive recommendation. The treatment algorithm is based on the recommendations for the management of unruptured aneurysms of the German Society of Neurosurgery (2) which are derived from the data of the International Study of Unruptured Intracranial Aneurysms (ISUIA studies) (3, 4) and the guidelines of the medical societies. In both disciplines, the treatment was carried out by colleagues with many years of experience. The data were deliberately evaluated using purely descriptive methods since the intention was to demonstrate that these are complementary treatment modalities which only provide the best results when patients are specifically selected for each procedure.

Periprocedural management
Craniotomy for clipping the aneurysm was performed in a manner suited to the localization in a standardized microsurgical procedure. The endovascular treatment was also performed under general anesthesia. To document treatment associated complications such as bleeding or infarctions, cranial computed tomography was routinely performed after 24 to 48 hours. In the event of thromboembolic complications, magnetic resonance imaging was also performed.

The success of aneurysm obliteration in the endovascularly treated patients was documented at the end of the neuroradiological intervention. In all operated patients, control angiography was performed between day 7 and day 10. Obliteration was assessed as follows: complete occlusion (no residual filling of the aneurysm and neck of aneurysm), small residue (occlusion with small residue at aneurysm neck) or residual aneurysm (residual filling of the aneurysm) (5). In the first few years, all patients with endovascularly treated UIA underwent digital subtraction angiography (DSA) over the course of 6 months. Over the last few years follow-up magnetic resonance angiography (MRA) has been performed after 6 months. In addition, MRA was recommended after 2 and 5 years.

The follow-up clinical examination was performed between 3 and 6 months after the treatment and patient outcome was recorded using the modified Rankin Scale (mRS) (6, 7) which describes the patient's clinical condition based on specific criteria.

Results
The clinical symptoms and the reason for performing DSA are shown in table 2 gif ppt. It is notable that unspecific clinical symptoms such as headache, dizziness or other complaints that prompted the use of MRI or CT diagnostic procedures which disclosed the presence of an unruptured aneurysm were much more common than specific focal neurological abnormalities. The patient specific data (age, gender and patients with multiple aneurysms) as well as aneurysm specific characteristics are shown in table 3 gif ppt. There were no conspicuous differences as regards the size of the treated aneurysms. Patients with multiple aneurysms were more often treated microsurgically. Table 4 gif ppt presents the type of treatment according to the localization of the aneurysms. This clearly shows that all so-called transitional aneurysms arising from the cavernous sinus and extending intradurally were treated endovascularly. Aneurysms of the posterior circulation (vertebrobasilar system) as well as paraclinoid aneurysms were more frequently treated endovascularly. In contrast, almost all aneurysms of the middle cerebral artery were treated microsurgically. There were no appreciable differences for the other sites.

Complete clip occlusion was achieved in 90.3% (149 of 165 UIA) (e-figure 1 jpg ppt). In 11 (6.7%) aneurysms the clip was intentionally placed at a short distance from the carrier vessel or the efferent branches to avoid stenosing the vessel. This was especially the case for complex aneurysms with partial calcification in which the entire base of the aneurysm had to be reconstructed with different clips. In 5 cases the aneurysm was wrapped. Of the microsurgically treated aneurysms with a small residue and the wrapped aneurysms, 8 (50%) underwent repeat angiography over the course of 6 months and showed no changes.

The endovascular treatment was performed for 58 aneurysms by placing and anchoring platinum coils in the aneurysm. Nine patients additionally required the implantation of a vascular stent, and 8 patients required coiling with the balloon reconstruction technique in order to achieve adequate occlusion of the aneurysm and prevent the coil becoming dislocated into the carrier vessel. Occlusion of the carrier vessel was performed in 4 patients after an occlusion test. 47 of the 80 endovascularly treated aneurysms (58.8%) were occluded completely (e-figure 2 jpg ppt). In 33 (41.2%) a minimal residue was detectable at the base. Sufficient occlusion was achieved for all aneurysms such that no residual perfusion within the aneurysmal sac was detectable (e-table 2 gif ppt). For the endovascularly treated aneurysms, follow-up angiographic evaluation revealed recanalization of the aneurysm with partial filling in 7 patients, necessitating repeat endovascular treatment. Three of these patients initially had complete occlusion, and in 4 patients a small residue was visible. In 3 further patients with a small residue after coiling, spontaneous obliteration of the residue occurred during the further course. The treatment objective of bleeding prophylaxis was achieved in all patients with the exception of one female patient with a complex basilar aneurysm which was treated with a flow modifying stent. After 12 months, this patient suffered SAB from the previously treated aneurysm.

Complications during the course of treatment (table 5 gif ppt) were not essentially different in the two treatment groups. There were no treatment related mortalities. De novo neurological deficits were due mainly to cerebral ischemia or minor periprocedural bleeding. The rate of symptomatic ischemia after clipping and coiling was 2.4% and 3.7%, respectively. Periprocedural thromboembolic complications after endovascular therapy were treated by the intra-arterial use of antiplatelet medications (glycoprotein IIb/IIIa receptor antagonists) in half of the thromboembolisms without ischemic deficits.

After surgical therapy, 2 patients (1.2%) developed symptomatic bleeding. One aneurysm ruptured during the endovascular procedure, but without rupture related morbidity in the long-term course. The course of treatment was very good to good in the great majority of patients. Regardless of the treatment modality, 98.8% of all treated aneurysms (n = 245) and 98.5% of all patients (n = 200) had a postprocedural mRS <=2 (table 6 gif ppt).

Discussion
Two basic questions arise regarding the treatment of patients with unruptured intracranial aneurysms. Is the treatment of this aneurysm indicated in this specific patient and, which is the most suitable treatment in this particular case to achieve permanent aneurysm occlusion with the lowest periprocedural risk? Even after publication of the prospective ISUIA data (4), the evidence situation for establishing the indication for treatment and selecting the suitable treatment modality remains modest due to the presence of selection bias and cannot be improved by the results reported here. The aim of this study was to present an overview of the results of treatment in a large patient sample at a specialized neurovascular center in which the two treatment modalities are available on the basis of an interdisciplinary consensus and used in a complementary manner.

The decision whether to treat or observe a patient must be based on a consideration of both patient and aneurysm specific factors. The basic requirement is to weigh the risks associated with aneurysm rupture with potentially fatal SAB against the risks of treatment (e-table 3 gif ppt). Besides the localization and size of the aneurysm, age and previous SAB are important criteria for establishing the indication for treatment. In accordance with the guidelines of the medical societies, treatment is justified for asymptomatic aneurysms of the anterior circulation from a size of 7 mm onwards, and also for symptomatic intradural aneurysms or previous SAB from a different aneurysm. Asymptomatic aneurysms of the posterior circulation – including aneurysms of the carotid artery at the origin of the posterior communicating artery – also justify an intervention. As a general principle, the indication for treatment should always be considered in relation to the patient's age and state of health (figure 2 gif ppt). A relative indication for treatment may also be present for incidental aneurysms <7 mm in diameter if there is a family history of aneurysmal disease or if the aneurysm has increased in size or changed its configuration in the follow-up examination.

In our patient series none of the patients died of the treatment and the treatment associated morbidity with poor outcome (mRS = 3–5) was only 1.2% (2 of 165 clipped aneurysms and 1 of 80 endovascularly treated aneurysms). The treatment results presented here are therefore better than those in the ISUIA studies (3, 4) and show good consistency with the results of other series (819). An analysis of the results over the time course shows that compared to the first segment of the series with recently published data (20), no relevant morbidity occurred within the last 20 months. The use of new surgical techniques (intraoperative indocyanine green angiography [21–23], continuous intraoperative monitoring [24], vascular navigation [25]) and new endovascular techniques (e1e4) is leading to an improvement in safety in the treatment of UIA.

The ISUIA studies provide no information regarding the rate of completely obliterated aneurysms. In the series presented here, complete occlusion without small neck residue was successful in 58.8% of the endovascularly and 90.3% of the surgically treated patients. Because of the relatively short follow-up time, the results of the endovascular treatment are only preliminary and require further evaluation in terms of the effectiveness of bleeding prophylaxis in the long-term course. The surgically treated aneurysms with a small neck residue were large, in some cases calcified aneurysms in which either the carrier vessel or afferent vascular branches were involved in the aneurysm. Wrapping, an alternative mode of treatment for unclippable aneurysms, was performed in 5 patients (3% of the UIA) (e5). Although a small residue was left at the base of the aneurysm in reconstruction of the vessels and clip occlusion of a complex aneurysm in order to prevent ischemic deficits, this was found to be stable in the follow-up examinations.

Our data also show that certain aneurysm sites primarily favor one form of treatment. For example, all aneurysms that begin in the cavernous sinus and extending intradurally (transitional aneurysms) and the majority of aneurysms in the region supplied by the vertebrobasilar artery were treated by the endovascular technique. The paraclinoid aneurysms were also more frequently treated surgically. Almost all aneurysms of the middle cerebral artery were treated surgically. The experience that aneurysms of the middle cerebral artery are better treated surgically is consistent with the treatment results obtained at other centers (e6, e7).

In conclusion, it should be mentioned that without randomization naturally no direct comparison was possible between neurosurgical and endovascular treatment of unruptured aneurysms. A competitive comparison of this kind between two treatment modalities is no longer up to date, and the two therapeutic approaches should be regarded as complementary. The two interventions also generate similar costs and are adequately covered by the Diagnosis Related Groups (DRG) remuneration system and coils by additional payments. Although such comparative cost calculations were not performed directly for the treatment of UIA, it was shown that there was no significant difference in costs for patients with ruptured aneurysm and SAB (e8). A discussion of costs of treatment versus costs of conservative therapy is very difficult to conduct and can only be poorly substantiated in view of the lack of data.

In patients with small unruptured aneurysms of the anterior circulation, the treatment outcome in the ISUIA study (4) was independent of the treatment modality. This fact underlines the importance of a careful, interdisciplinary consideration of the suitable therapeutic approach taking into account patient age, aneurysm size and configuration and comorbidity. Patients with large, complex aneurysms – defined by vessels originating at the base – will have to continue being treated microsurgically, with a significantly higher level of technical difficulty and correspondingly greater demands on the microsurgical skills of the surgeon. The data presented here show that even with these aneurysms, surgical therapy offering a very good outcome and a low rate of complications is possible at a specialized center. The most important point, however, is that a non-competitive discussion of each individual aneurysm by a team of experienced neurosurgeons and neuroradiologists is indispensable for establishing whether there is an indication for treatment in a specific case and which procedure is the safest and most promising.

Conclusion
Unruptured intracranial aneurysms can be treated surgically or endovascularly with low morbidity and a very good clinical and angiographic outcome. Complex and partially calcified aneurysms with involvement of a carrier vessel or vascular branches are more suitable for surgical treatment. The treatment of patients with unruptured aneurysms should be carried out at specialized centers handling large numbers of cases and with corresponding endovascular and neurosurgical experience. It should be carried out only after an interdisciplinary case discussion and a joint decision regarding the optimal treatment modality and taking into consideration all the risks.

Acknowledgement
We express our thanks to Ms. Marina Eberhardt for her support with designing the diagrams and Ms. Anne Sicking for her assistance in maintaining the database.

Conflict of interest statement
The authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript received on 17 August 2007, revised version accepted on 6 February 2008.

Translated from the original German by mt-g.

Corresponding author
Prof. Dr. med. Volker Seifert
PD Dr. med. Rüdiger Gerlach
Klinik für Neurochirurgie
Johann Wolfgang Goethe-Universität
Schleusenweg 2–16
60528 Frankfurt/Main, Germany
r.gerlach@em.uni-frankfurt.de
1.
Vernooij MW, Ikram MA, Tanghe HL et al.: Incidental findings on brain MRI in the general population. N Engl J Med 2007; 357: 1821–8.
2.
Raabe A, Beck J, Berkefeld J et al.: Recommendations for the management of patients with aneurysmal subarachnoid hemorrhage. Zentralbl Neurochir 2005; 66: 79–91.
3.
Unruptured intracranial aneurysms–risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators. N Engl J Med 1998; 339: 1725–33.
4.
Wiebers DO, Whisnant JP, Huston J et al.: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362: 103–10.
5.
Raymond J, Guilbert F, Roy D: Neck-bridge device for endovascular treatment of wide-neck bifurcation aneurysms: initial experience. Radiology 2001; 221: 318–26.
6.
Bonita R, Beaglehole R: Recovery of motor function after stroke. Stroke 1988; 19: 1497–500.
7.
Rankin J: Cerebral vascular accidents in patients over the age of 60. II. Prognosis. Scott Med J 1957; 2: 200–15.
8.
Moroi J, Hadeishi H, Suzuki A, Yasui N: Morbidity and mortality from surgical treatment of unruptured cerebral aneurysms at Research Institute for Brain and Blood Vessels – Akita. Neurosurgery 2005; 56: 224–31.
9.
Wanke I, Doerfler A, Dietrich U et al.: Endovascular treatment of unruptured intracranial aneurysms. Am J Neuroradiol 2002; 23: 756–61.
10.
Gonzalez N, Murayama Y, Nien YL et al.: Treatment of unruptured aneurysms with GDCs: clinical experience with 247 aneurysms. Am J Neuroradiol 2004; 25: 577–83.
11.
Goddard AJ, Annesley-Williams D, Gholkar A: Endovascular management of unruptured intracranial aneurysms: does outcome justify treatment? J Neurol Neurosurg Psychiatry 2002; 72: 485–90.
12.
Orz YI, Hongo K, Tanaka Y et al.: Risks of surgery for patients with unruptured intracranial aneurysms. Surg Neurol 2000; 53: 21–7.
13.
Ogilvy CS, Carter BS: Stratification of outcome for surgically treated unruptured intracranial aneurysms. Neurosurgery 2003; 52: 82–7.
14.
King JT Jr, Berlin JA, Flamm ES: Morbidity and mortality from elective surgery for asymptomatic, unruptured, intracranial aneurysms: a meta-analysis. J Neurosurg 1994; 81: 837–42.
15.
Solomon RA, Fink ME, Pile-Spellman J: Surgical management of unruptured intracranial aneurysms. J Neurosurg 1994; 80: 440–6.
16.
Raftopoulos C, Goffette P, Vaz G et al.: Surgical clipping may lead to better results than coil embolization: results from a series of 101 consecutive unruptured intracranial aneurysms. Neurosurgery 2003; 52: 1280–7.
17.
Taha MM, Nakahara I, Higashi T et al.: Endovascular embolization vs surgical clipping in treatment of cerebral aneurysms: morbidity and mortality with short-term outcome. Surg Neurol 2006; 66: 277–84.
18.
Raaymakers TW, Rinkel GJ, Limburg M, Algra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998; 29: 1531–8.
19.
Krisht AF, Gomez J, Partington S: Outcome of surgical clipping of unruptured aneurysms as it compares with a 10-year non-clipping survival period. Neurosurgery 2006; 58: 207–16.
20.
Gerlach R, Beck J, Setzer M et al.: Treatment related morbidity of unruptured intracranial aneurysms: results of a prospective single centre series with an interdisciplinary approach over a 6 year period (1999–2005). J Neurol Neurosurg Psychiatry 2007; 78: 864–71.
21.
Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V: Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery 2003; 52: 132–9.
22.
Raabe A, Nakaji P, Beck J et al.: Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 2005; 103: 982–9.
23.
Raabe A, Beck J, Seifert V: Technique and image quality of intraoperative indocyanine green angiography during aneurysm surgery using surgical microscope integrated near-infrared video technology. Zentralbl Neurochir 2005; 66: 1–6.
24.
Szelenyi A, Langer D, Kothbauer K, De Camargo AB, Flamm ES, Deletis V: Monitoring of muscle motor evoked potentials during cerebral aneurysm surgery: intraoperative changes and postoperative outcome. J Neurosurg 2006; 105: 675–81.
25.
Raabe A, Beck J, Rohde S, Berkefeld J, Seifert V: Three-dimensional rotational angiography guidance for aneurysm surgery. J Neurosurg 2006; 105: 406–11.
e1.
Pouratian N, Oskouian RJ Jr, Jensen ME, Kassell NF, Dumont AS: Endovascular management of unruptured intracranial aneurysms. J Neurol Neurosurg Psychiatry 2006; 77: 572–8.
e2.
Weber W, Siekmann R, Kis B, Kuehne D: Treatment and follow-up of 22 unruptured wide-necked intracranial aneurysms of the internal carotid artery with Onyx HD 500. Am J Neuroradiol 2005; 26: 1909–15.
e3.
Malek AM, Halbach VV, Phatouros CC et al.: Balloon-assist technique for endovascular coil embolization of geometrically difficult intracranial aneurysms. Neurosurgery 2000; 46: 1397–406.
e4.
Vallee JN, Pierot L, Mont'alverne F et al.: Unruptured intracranial aneurysms treated by three-dimensional coil embolization: evaluation of the postoperative aneurysm occlusion volume. Neuroradiology 2005; 47: 438–45.
e5.
Deshmukh VR, Kakarla UK, Figueiredo EG, Zabramski JM, Spetzler RF: Long-term clinical and angiographic follow-up of unclippable wrapped intracranial aneurysms. Neurosurgery 2006; 58: 434–42.
e6.
Regli L, Uske A, de Tribolet N: Endovascular coil placement compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: a consecutive series. J Neurosurg 1999; 90: 1025–30.
e7.
Regli L, Dehdashti AR, Uske A, de Tribolet N: Endovascular coiling compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: an update. Acta Neurochir Suppl 2002; 82: 41–6.
e8.
Wolstenholme J, Rivero-Arias O, Gray A et al.: Treatment pathways, resource use, and costs of endovascular coiling versus surgical clipping after aSAH. Stroke 2008; 39: 111–9.
e9.
Diener HC et al.: Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Georg Thieme Verlag, 2005.
Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Klinik für Neurochirurgie: Prof. Dr. med. Seifert, PD Dr. med. Gerlach, Prof. Dr. med. Raabe, Dr. med. Güresir, PD Dr. med. Beck, Dr. med Szelényi, Dr. med. Setzer, PD Dr. med. Vatter Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Institut für Neuroradiologie: PD Dr. med. Du Mesnil de Rochemont, Prof. Dr. med. Zanella, Prof. Dr. med. Berkefeld Klinikum Herford, Anstalt des öffentlichen Rechts, Klinik für Neurologie, Herford: Prof. Dr. med. Sitzer *Volker Seifert und Rüdiger Gerlach teilen sich die Erstautorenschaft
1. Vernooij MW, Ikram MA, Tanghe HL et al.: Incidental findings on brain MRI in the general population. N Engl J Med 2007; 357: 1821–8.
2. Raabe A, Beck J, Berkefeld J et al.: Recommendations for the management of patients with aneurysmal subarachnoid hemorrhage. Zentralbl Neurochir 2005; 66: 79–91.
3. Unruptured intracranial aneurysms–risk of rupture and risks of surgical intervention. International Study of Unruptured Intracranial Aneurysms Investigators. N Engl J Med 1998; 339: 1725–33.
4. Wiebers DO, Whisnant JP, Huston J et al.: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003; 362: 103–10.
5. Raymond J, Guilbert F, Roy D: Neck-bridge device for endovascular treatment of wide-neck bifurcation aneurysms: initial experience. Radiology 2001; 221: 318–26.
6. Bonita R, Beaglehole R: Recovery of motor function after stroke. Stroke 1988; 19: 1497–500.
7. Rankin J: Cerebral vascular accidents in patients over the age of 60. II. Prognosis. Scott Med J 1957; 2: 200–15.
8. Moroi J, Hadeishi H, Suzuki A, Yasui N: Morbidity and mortality from surgical treatment of unruptured cerebral aneurysms at Research Institute for Brain and Blood Vessels – Akita. Neurosurgery 2005; 56: 224–31.
9. Wanke I, Doerfler A, Dietrich U et al.: Endovascular treatment of unruptured intracranial aneurysms. Am J Neuroradiol 2002; 23: 756–61.
10. Gonzalez N, Murayama Y, Nien YL et al.: Treatment of unruptured aneurysms with GDCs: clinical experience with 247 aneurysms. Am J Neuroradiol 2004; 25: 577–83.
11. Goddard AJ, Annesley-Williams D, Gholkar A: Endovascular management of unruptured intracranial aneurysms: does outcome justify treatment? J Neurol Neurosurg Psychiatry 2002; 72: 485–90.
12. Orz YI, Hongo K, Tanaka Y et al.: Risks of surgery for patients with unruptured intracranial aneurysms. Surg Neurol 2000; 53: 21–7.
13. Ogilvy CS, Carter BS: Stratification of outcome for surgically treated unruptured intracranial aneurysms. Neurosurgery 2003; 52: 82–7.
14. King JT Jr, Berlin JA, Flamm ES: Morbidity and mortality from elective surgery for asymptomatic, unruptured, intracranial aneurysms: a meta-analysis. J Neurosurg 1994; 81: 837–42.
15. Solomon RA, Fink ME, Pile-Spellman J: Surgical management of unruptured intracranial aneurysms. J Neurosurg 1994; 80: 440–6.
16. Raftopoulos C, Goffette P, Vaz G et al.: Surgical clipping may lead to better results than coil embolization: results from a series of 101 consecutive unruptured intracranial aneurysms. Neurosurgery 2003; 52: 1280–7.
17. Taha MM, Nakahara I, Higashi T et al.: Endovascular embolization vs surgical clipping in treatment of cerebral aneurysms: morbidity and mortality with short-term outcome. Surg Neurol 2006; 66: 277–84.
18. Raaymakers TW, Rinkel GJ, Limburg M, Algra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998; 29: 1531–8.
19. Krisht AF, Gomez J, Partington S: Outcome of surgical clipping of unruptured aneurysms as it compares with a 10-year non-clipping survival period. Neurosurgery 2006; 58: 207–16.
20. Gerlach R, Beck J, Setzer M et al.: Treatment related morbidity of unruptured intracranial aneurysms: results of a prospective single centre series with an interdisciplinary approach over a 6 year period (1999–2005). J Neurol Neurosurg Psychiatry 2007; 78: 864–71.
21. Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V: Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery 2003; 52: 132–9.
22. Raabe A, Nakaji P, Beck J et al.: Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 2005; 103: 982–9.
23. Raabe A, Beck J, Seifert V: Technique and image quality of intraoperative indocyanine green angiography during aneurysm surgery using surgical microscope integrated near-infrared video technology. Zentralbl Neurochir 2005; 66: 1–6.
24. Szelenyi A, Langer D, Kothbauer K, De Camargo AB, Flamm ES, Deletis V: Monitoring of muscle motor evoked potentials during cerebral aneurysm surgery: intraoperative changes and postoperative outcome. J Neurosurg 2006; 105: 675–81.
25. Raabe A, Beck J, Rohde S, Berkefeld J, Seifert V: Three-dimensional rotational angiography guidance for aneurysm surgery. J Neurosurg 2006; 105: 406–11.
e1. Pouratian N, Oskouian RJ Jr, Jensen ME, Kassell NF, Dumont AS: Endovascular management of unruptured intracranial aneurysms. J Neurol Neurosurg Psychiatry 2006; 77: 572–8.
e2. Weber W, Siekmann R, Kis B, Kuehne D: Treatment and follow-up of 22 unruptured wide-necked intracranial aneurysms of the internal carotid artery with Onyx HD 500. Am J Neuroradiol 2005; 26: 1909–15.
e3. Malek AM, Halbach VV, Phatouros CC et al.: Balloon-assist technique for endovascular coil embolization of geometrically difficult intracranial aneurysms. Neurosurgery 2000; 46: 1397–406.
e4. Vallee JN, Pierot L, Mont'alverne F et al.: Unruptured intracranial aneurysms treated by three-dimensional coil embolization: evaluation of the postoperative aneurysm occlusion volume. Neuroradiology 2005; 47: 438–45.
e5. Deshmukh VR, Kakarla UK, Figueiredo EG, Zabramski JM, Spetzler RF: Long-term clinical and angiographic follow-up of unclippable wrapped intracranial aneurysms. Neurosurgery 2006; 58: 434–42.
e6. Regli L, Uske A, de Tribolet N: Endovascular coil placement compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: a consecutive series. J Neurosurg 1999; 90: 1025–30.
e7. Regli L, Dehdashti AR, Uske A, de Tribolet N: Endovascular coiling compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: an update. Acta Neurochir Suppl 2002; 82: 41–6.
e8. Wolstenholme J, Rivero-Arias O, Gray A et al.: Treatment pathways, resource use, and costs of endovascular coiling versus surgical clipping after aSAH. Stroke 2008; 39: 111–9.
e9. Diener HC et al.: Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Georg Thieme Verlag, 2005.