Skip to main content
SpringerLink
Log in

Long-term prognosis in patients with clipped unruptured cerebral aneurysms―increased cerebrovascular events in patients with surgically treated unruptured aneurysms

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

We retrospectively investigated surgical immediate and long-term overall results after clipping of the unruptured aneurysms. Between 1991 and 2008, 166 patients underwent neck clipping of unruptured saccular aneurysms at our institute. Patients were subsequently followed to clarify the occurrence of subarachnoid hemorrhage (SAH), and stroke other than SAH, aneurysm recurrence, cerebrovascular death, all-cause death, and risk factors. Surgical complication was noted in 14 patients (8.4 %) and surgical morbidity in two patients (1.2 %). Of 164 patients except for these two patients who suffered surgical morbidity, we could obtain more than 3 years follow-up information for 144 patients (87.8 %). There were 49 men and 95 women. The mean age was 58.5 years, and mean follow-up period was 7.9 years. Eight cases had died during follow-up (hepatic insufficiency in one, renal insufficiency in one, suicide in one, intracerebral hemorrhage (ICH) in two, SAH in one, and pneumonia after stroke in two). Therefore, the cause of death was stroke and late effects of stroke. Twelve symptomatic cerebrovascular events (cerebral infarction in seven, ICH in four, and SAH in one) occurred in ten patients. Consequently, annual risk of SAH after clipping of unruptured aneurysms was 0.085 %. Besides, annual risk of stroke in those patients was 1.06 %, and this incidence was higher than that in the general population. Although this study confirmed the good surgical result, annual risk of stroke after clipping of unruptured aneurysms was much higher than that in the general population. The long-term periodic examination to detect recurrent aneurysms and appropriate management to prevent stroke should be performed for patients with surgically treated unruptured aneurysm.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akiyama Y, Houkin K, Nozaki K, Hashimoto N (2010) Practical decision-making in the treatment of unruptured cerebral aneurysm in Japan: the U-CARE study. Cerebrovasc Dis 30:491–499

    Article  PubMed  Google Scholar 

  2. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N (2008) Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats. Stroke 39:1276–1285

    Article  PubMed  CAS  Google Scholar 

  3. Bruneau M, Rynkowski M, Smida-Rynkowska K, Brotchi J, De Witte O, Lubicz B (2011) Long-term follow-up survey reveals a high yield, up to 30 % of patients presenting newly detected aneurysms more than 10 years after ruptured intracranial aneurysms clipping. Neurosurg Rev 34(4):485–496

    Article  PubMed  Google Scholar 

  4. Chyatte D, Bruno G, Desai S, Todor DR (1999) Inflammation and intracranial aneurysms. Neurosurgery 45:1137–1146, discussion 1146–1137

    Article  PubMed  CAS  Google Scholar 

  5. David CA, Vishteh AG, Spetzler RF, Lemole M, Lawton MT, Partovi S (1999) Late angiographic follow-up review of surgically treated aneurysms. J Neurosurg 91:396–401

    Article  PubMed  CAS  Google Scholar 

  6. Edner G, Almqvist H (2007) The Stockholm 20-year follow-up of aneurysmal subarachnoid hemorrhage outcome. Neurosurgery 60:1017–1024, 1010.1227/1001.NEU.0000255458.0000207140.E0000255456

    Article  PubMed  Google Scholar 

  7. Hadeishi H, Yasui N, Suzuki A (1991) Risks of surgical treatment for unruptured intracranial aneurysms. No Shinkei Geka 19:945–949

    PubMed  CAS  Google Scholar 

  8. Hata J, Doi Y, Ninomiya T, Fukuhara M, Ikeda F, Mukai N, Hirakawa Y, Kitazono T, Kiyohara Y (2011) Combined effects of smoking and hypercholesterolemia on the risk of stroke and coronary heart disease in Japanese: the Hisayama study. Cerebrovasc Dis 31(5):477–484

    Article  PubMed  Google Scholar 

  9. Heiskanen O, Poranen A (1987) Surgery of incidental intracranial aneurysms. Surg Neurol 28:432–436

    Article  PubMed  CAS  Google Scholar 

  10. Juvela S, Poussa K, Porras M (2001) Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke 32:485–491

    Article  PubMed  CAS  Google Scholar 

  11. Morita A (2002) On-line outcome study of unruptured cerebral aneurysm in Japan (UCAS Japan). Rinsho Shinkeigaku 42:1188–1190

    PubMed  Google Scholar 

  12. Morita A, Fujiwara S, Hashi K, Ohtsu H, Kirino T (2005) Risk of rupture associated with intact cerebral aneurysms in the Japanese population: a systematic review of the literature from Japan. J Neurosurg 102:601–606

    Article  PubMed  Google Scholar 

  13. Morita A, Kimura T, Sora S (2009) Clinical standard of neurosurgical disorder (5): management of the unruptured intracranial aneurysms. No Shinkei Geka 37:399–411

    PubMed  Google Scholar 

  14. Nieuwkamp DJ, Algra A, Blomqvist P, Adami J, Buskens E, Koffijberg H, Rinkel GJ (2011) Excess mortality and cardiovascular events in patients surviving subarachnoid hemorrhage: a nationwide study in Sweden. Stroke 42:902–907

    Article  PubMed  Google Scholar 

  15. Pera J, Korostynski M, Krzyszkowski T, Czopek J, Slowik A, Dziedzic T, Piechota M, Stachura K, Moskala M, Przewlocki R, Szczudlik A (2010) Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation? Stroke 41(2):224–231

    Article  PubMed  CAS  Google Scholar 

  16. Raaymakers TW, Rinkel GJ, Limburg M, Algra A (1998) Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 29:1531–1538

    Article  PubMed  CAS  Google Scholar 

  17. Suzuki K (2008) Stroke register in Akita: incidence and the burden of diseases. Nihon Ronen Igakkai Zasshi 45:169–171

    Article  PubMed  Google Scholar 

  18. Suzuki K (2009) Calculation of stroke events in Japan from 2005 to 2055. Sougou Rinshou 58:194–198

    Google Scholar 

  19. Tsutsumi K, Ueki K, Morita A, Usui M, Kirino T (2001) Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results of long-term follow-up angiography. Stroke 32:1191–1194

    Article  PubMed  CAS  Google Scholar 

  20. Tsutsumi K, Ueki K, Usui M, Kwak S, Kirino T (1998) Risk of recurrent subarachnoid hemorrhage after complete obliteration of cerebral aneurysms. Stroke 29:2511–2513

    Article  PubMed  CAS  Google Scholar 

  21. Tsutsumi K, Ueki K, Usui M, Kwak S, Kirino T (1999) Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms. Stroke 30:1181–1184

    Article  PubMed  CAS  Google Scholar 

  22. van der Schaaf IC, Velthuis BK, Wermer MJH, Majoie C, Witkamp T, de Kort G, Freling NJ, Rinkel GJE, on behalf of the ASG (2005) New detected aneurysms on follow-up screening in patients with previously clipped intracranial aneurysms: comparison with DSA or CTA at the time of SAH. Stroke 36:1753–1758

    Article  PubMed  Google Scholar 

  23. Wermer MJH, Greebe P, Algra A, Rinkel GJE (2005) Incidence of recurrent subarachnoid hemorrhage after clipping for ruptured intracranial aneurysms. Stroke 36:2394–2399

    Article  PubMed  Google Scholar 

  24. Wermer MJH, van der Schaaf IC, Velthuis BK, Algra A, Buskens E, Rinkel GJE (2005) Follow-up screening after subarachnoid hemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain 128:2421–2429

    Article  PubMed  CAS  Google Scholar 

  25. Wiebers DO, Piepgras DG, Brown RD Jr, Meissner I, Torner J, Kassell NF, Whisnant JP, Huston J 3rd, Nichols DA (2002) Unruptured aneurysms. J Neurosurg 96:50–51, discussion 58–60

    Article  PubMed  Google Scholar 

  26. Wiebers DO, Whisnant JP, Huston J 3rd, Meissner I, Brown RD Jr, Piepgras DG, Forbes GS, Thielen K, Nichols D, O’Fallon WM, Peacock J, Jaeger L, Kassell NF, Kongable-Beckman GL, Torner JC (2003) Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103–110

    Article  PubMed  Google Scholar 

  27. Yonekura M (2004) Small unruptured aneurysm verification (SUAVe Study, Japan)–interim report. Neurol Med Chir (Tokyo) 44:213–214

    Article  Google Scholar 

Download references

Conflict of Interest

There is no conflict of interest to report.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan

    Masaaki Hokari, Satoshi Kuroda, Naoki Nakayama & Kiyohiro Houkin

  2. Department of Surgical Neurology, Research Institute for Brain and Blood Vessels-Akita, Akita, Japan

    Tatsuya Ishikawa

  3. Department of Neurosurgery, Asahikawa Red Cross Hospital, Asahikawa, Japan

    Hiroyasu Kamiyama

Authors
  1. Masaaki Hokari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoshi Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoki Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kiyohiro Houkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tatsuya Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroyasu Kamiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masaaki Hokari.

Additional information

Comments

Kazuhiro Hongo, Matsumoto, Japan

This is a paper describing the long-term prognosis in patients with clipped unruptured cerebral aneurysms, and the authors found that annual risk of SAH after clipping of unruptured aneurysm was 0.085 %, and annual risk of stroke in those patients was 1.06 %, and this incidence was higher than that in the general population. They also found that history of stroke was more frequent in the stroke after clipping group (P = 0.018). The incidence of risk factors such as hypertension, diabetes mellitus, and dyslipidemia in the patients of this study was ordinary as the general population. These results are valuable, and the authors gave us an important message. Even for patients with unrutpured aneurysms, long-tem follow-up is needed after clipping surgery. Neurosurgeons especially those who deal with stroke need to know these results.

John Braca, Christopher M. Loftus, Maywood, USA

As patient selection, preoperative risk optimization and immediate surgical outcomes improve in patients with surgical clipping of aneurysms, there will be a need to assess and scrutinize the long-term outcomes of these patients. Identifying patients that are in a high-risk group for cerebrovascular events and effectively getting the patient’s medical treatment to optimize their health will prove to be one of the next challenges in modern cerebrovascular surgery. In the present report, Masaaki Hokari et al. from the very experienced Hokkaido University group have described their findings in a Japanese population of patients with unruptured intracranial aneurysms following clipping.

Strategically excluding patients with more complex aneurysms requiring bypass techniques and ruptured intracranial aneurysms may allow a clearer picture of the patients’ long-term risk of postsurgical clipping. Of note, immediate surgical complications were tallied by including postoperative events 3 months after surgery as opposed to 1 month.

The authors correctly point out a limitation in their study as they acknowledged the short follow up time period. In addition, the relatively small sample size may limit the statistical relevance of their findings. Although, with the current data set, a more detailed table including aneurysm location and size as well as possible correlation with stroke laterality would be helpful to divide this group into subcohorts for further analysis. Continuing to analyze this data may elucidate the more high-risk locations of unruptured aneurysms that undergo surgical treatment.

The underlying histopathology of aneurysm formation underscores the importance of serial follow up of patients with cerebral aneurysms. “Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a proinflammatory phenotype.”1 Hokari et al. point out that even with their incomplete follow up, there were six de novo aneurysms that were detected. Based on this accumulating data, patients with intracranial aneurysms should conceivably be considered life-long patients.

When examining the histopathological data available for clipped aneurysms, the following conclusion was made by Killer-Oberpfalzer et al.: “The effectiveness of aneurysm clipping is related to the mechanics of aneurysm exclusion rather than the processes of endothelialization and neointima formation.”3 The implication of the genetic predisposition for patients with intracranial aneurysms to have a milieu conducive to other cerebrovascular diseases (i.e., stroke) has been described as the authors point out. 2, 4 Perhaps, the mechanical apposition of healthy endothelium remains as the most durable method of excluding an intracranial aneurysm from the circulation. Indeed, histological evidence of inflammation seen at the unruptured aneurysm neck following clipping3 alludes to a primary vessel pathology or a vessel segment that is susceptible to genetic expression of inflammatory biomolecules that can permit aneurysm recurrence or serve as a nidus for thrombotic/embolic events.

Postoperatively, patients are being successfully protected from a more immediate threat (risk of intracranial aneurysm rupture). However, as this new evidence mounts, surgeons need to stay ahead of the curve by shifting the focus from immediate postoperative care to educating patients about their comorbid conditions and the long-term natural history of cerebrovascular disease. In order to assist the ever-increasing workload of neurosurgeons, perhaps future efforts should be placed in forming multidisciplinary clinics specializing in the long-term care for patients with surgically clipped aneurysms to encourage life-long care and disease prevention.

References

1. Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, Koch WJ, Dumont AS. Biology of intracranial aneurysms: role of inflammation. J Cereb Blood Flow Metab. 2012 Sep;32(9):1659–76. doi:10.1038/jcbfm.2012.84. Epub 2012 Jul 11.

2. Chyatte D, Bruno G, Desai S, Todor DR. Inflammation and intracranial aneurysms. Neurosurgery 1999 45:1137–1146.

3. Killer-Oberpfalzer M, Aichholzer M, Weis S, Richling B, Jones R, Virmani R, Cruise GM. Histological analysis of clipped human intracranial aneurysms and parent arteries with short-term follow-up. Cardiovasc Pathol. 2012 Jul-Aug;21(4):299–306. doi: 10.1016/j.carpath.2011.09.010. Epub 2011 Nov 18.

4. Pera J, Korostynski M, Krzyszkowski T, Czopek J, Slowik A, Dziedzic T, Piechota M, Stachura K, Moskala M, Przewlocki R, Szczudlik A. Stroke. 2010 Feb;41(2):224–31. doi: 10.1161/STROKEAHA.109.562009. Epub 2009 Dec 31. Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation?

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hokari, M., Kuroda, S., Nakayama, N. et al. Long-term prognosis in patients with clipped unruptured cerebral aneurysms―increased cerebrovascular events in patients with surgically treated unruptured aneurysms. Neurosurg Rev 36, 567–572 (2013). https://doi.org/10.1007/s10143-013-0465-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-013-0465-y

Keywords

Search

Navigation