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

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.

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Correspondence to Masaaki Hokari.

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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.

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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?

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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

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

Keywords

  • Long-term prognosis
  • Clipping
  • Unruptured cerebral aneurysms
  • Stroke