Introduction

   The management of unruptured intracranial aneurysm (UIAs) has changed in recent years affected by such factors as improved understanding of the natural history of unruptured aneurysm, increased frequency of diagnosis of unruptured aneurysms by non-invasive image techniques, and establishment of endovascular coiling as an alternative to surgical clipping. Concerning about the natural history of UIAs, the bleeding risks was known to be 0.5-2.2 % per year.³⁾⁴⁾⁵⁾ However, great controversy on the bleeding risks of UIAs was evoked by the data of the International Study of Unruptured Intracranial Aneurysms (ISUIA), which reported much benign natural history of small size (<7 mm) UIAs and size and location were the important factors for determining bleeding risk.¹²⁾¹⁵⁾ Based on such risk factors of every individual UIA, it is very fundamental step in management of UIAs to determine whether preventive repair may be beneficial or not.
   For the unruptured aneurysms, noninvasive endovascular coiling rather than surgical clipping drew more attraction as primary treatment. However, no randomised study comparing endovascular coiling with surgical clipping for UIAs has yet available, even though a couple of data of prospective randomised studies for ruptured aneurysms are published.⁹⁾¹⁰⁾ And, although coil embolization was known to be effective in preventing rebleeding of ruptured aneurysms, generalization of this data to unruptured aneurysms has limitation because no long follow-up over 2 to 3 decade was yet made.
   The development of non-invasive imaging technique, like magnetic resonance angiography(MRA) or multi-slice computed tomography angiography (MDCTA), made the diagnose of UIAs possible without conventional digital subtraction angiography (DSA) in large number of cases and this non-invasive techniques contributed to increased detection of UIAs.
   In management of UIAs, a useful practical guideline should be provided in determining under what circumstances the preventative repair of UIAs would be beneficial and what means of treatment would be preferred.

Material and Methods

   We treated 151 unruptured intracranial aneurysms from January to December 2004, and the number of ruptured aneurysms was 332 during the same period. One hundred-six aneurysms of 151 UIAs were treated using endovascular coil technique. The annual numbers of UIAs in our hospital were 19, 7, 13, 29, 42, 50 from 1999 to 2004, and the annual number of UIAs treated by coiling were 5, 4, 8, 19, 30, 40 respectively. Both the number of UIAs and the number of UIAs treated by coils increased annually, particularly the coiling cases (Fig. 1). The locations of UIAs were anterior circulation in 120 cases and posterior circulation in 31. Eleven aneurysms presented with non-hemorrhagic mass symptoms. Endovasular coiling was used in 72 (60%) out of 120 anterior circulation UIAs and 30 (96.7%) out of 31 posterior circulation UIAs. Aneurysms of paraclinoidal carotid artery (ICA) and basilar artery were the most common and detailed distributions is on Table 1. The reasons of selection of endovascular coil method were anticipated surgical difficulty in 69, pre-determined by referral physicians in 17, poor medical conditions in 11, and patient's preference in 9. As neuro-endovascular procedures also has being performed by vascular neurosurgeons in our department, the decision in selecting treatment method in anticipated difficult surgical cases was made by neurosurgeons based on comparison the relative feasibility between clipping and coiling.

1. Endovascular Techniques and methods of evaluation
   Endovascular coiling procedures were performed under general anesthesia through a transfemoral route. After femoral sheath had been introduced, systemic heparinization was made by bolus injection of heparin 3000-5000 IU and 1000-2000 IU every our to maintain the activated clotting time (ACT) within 2.5 to 3 times of normal. Biplane Digital subtraction angiography (DSA) machine (VB 3000, Philips Co.) with rotational 3-dimension angiography function was used in all cases. A couple of different version of microcatheters produced by Boston Scientific Co^TM or Cordis^TM were used, case to case, using coaxial technique. For aneurysm embolization coils, various versions of Guglielmi Detachable Coils (GDCs, Boston Scientific Co.) were used in most case except some recent cases in which Orbit^TM coils(Cordis) were tried. Stent assisted coil technique was used in 22 cases (20.7%) and balloon assisted technique in 3 cases (2.8%)(Fig. 3). The immediate angiographic results of coil occlusion were described by "complete" with no contrast filling in body and neck of aneurysm, "neck remnants" with contrast filling in neck portion, and "incomplete" with contrast filling in body. Single follow-up angiographic study was obtained in 41 cases (38.6%) at 13,0 months mean period(5 to 22 months) and twice follow-up angiogram in 6. Clinical follow up was made in 81 cases and mean follow-up period was 16.9 months (8 to 37 months).

Results

1. Immediate angiographic outcomes and procedural complications
   Sixty-three (59.4%) aneurysms were smaller than 10mm in maximum aneurysm size, 30 (28.3%) aneurysms were 11-20 mm, and 13 (12.2%) were over 21 mm (Fig. 2). The immediate angiographic results were complete in 61(57.5%) aneurysms, neck remnants in 35 (33%) aneurysms, incomplete embolization in 7 (6.7%), and attempted and failed in 3 (2.8%). Of 63 aneurysms with small size (<10 mm), 45 (71.4%) resulted in complete occlusion, neck remnants in 15 (23.8%), incomplete occlusion in 1 (1.6%), and unsuccessful attempt in one. Of 30 aneurysms with 11-20 mm in size, 14 (46.7%) achieved complete occlusion, 13 (43.3%) resulted in neck remnants, 2 (6.7%) had complete occlusion, and 1 attempt only. Of 13 aneurysms sized over 21 mm, only 2 (15.4%) complete embolizations were obtained. Seven (53.8%) had neck remnants and 4 (30.8%) were incompletely embolized. There were 9 procedural complications, 6 thromboembolisms, 2 aneurysm perforations, and 1 coil migration. Two aneurysm perforations happened both in small size (<10 mm) aneurysms. Three of 6 thromboembolic complications were recanalized with intraarterial superselective thrombolysis and recovered clinically well. Aneurysmal bleeding of two perforated cases were controlled by completion of coiling and immediate reversal of heparinization, and eventually recovered well. However, three patients with thromboembolic complications and a coil migration patients were remained in permanent neurologic deficits, so morbidity rate was 3.8%.

2. Angiographic and clinical follow-up
   Forty-one angiographic follow-up cases included 18 (43.9%) cases of complete occlusion of immediate angiographic results, 18 (43.9%) cases of neck remnants, and 5 (12.2%) incomplete occlusion. Recanalization occurred in 2 out of 18 initially complete occlusion and they were subsequently reembolized. Among 18 aneurysms with neck remnants, 3 (16.7%) cases changed to complete occlusion by delayed thrombosis and 4 (22.2%) cases developed further recanalization by coil compaction. Three of these coil compactions were retreated by coiling, and achieved complete occlusion in two cases. Three out of 5 incompletely occluded cases showed no change and further coil compaction was noticed in two. Of 81 clinically followed up aneurysms, no delayed aneurysmal bleeding was experienced. four improved their previous symptoms associated to mass, 4 presented with remained neurological deficits, and the others were neurologically intact or remained unchanged.

Discussion

   Despite the significant improvement in the surgical and medical managements for aneurysmal subarachnoid hemorrhage(SAH), it is still serious disease with high mortality and morbidity because important part of its prognosis is determined by the severity of initial hemorrhage.³⁾⁴⁾⁵⁾ And, when UIAs were discovered incidentally, they has been operated for decades with expectation that the preventive repairing of aneurysm can eliminate this high mortality and morbidity caused by possible hemorrhage. However, the natural history and the risks associated with the surgical repair of UIAs were not sufficiently known. The bleeding risks of UIAs has been reported constantly to be within 1% to 3% for decades.³⁾⁴⁾⁷⁾ Since the data from the International Study of Unruptured Intracranial Aneurysms (ISUIA, Part 1, 1998 & Part 2, 2003) was published, great controversy has been evoked regarding to the natural history of UIAs.¹²⁾¹⁵⁾ In ISUIA 2, the rupture rate of for anterior circulation aneurysms <7 mm was 0% per year in patients with no prior SAH, and 0.3% per year in patients with previous SAH; 7-12 mm aneurysms, 0.5% per year in both groups; 13-24 mm aneurysms, 3% per year; and giant aneurysms 8% per year.
   Rupture rate for posterior circulation aneurysms were higher at all sizes; <7 mm was 0.5% per year in subjects with no prior SAH, 0.7% per year in patients with prior SAH; 7-12 mm, 3% per year; 13-24 mm, 3.7% per year; and giant aneurysms, 10% per year.¹²⁾ To summarize the ISUIA, the bleeding risk of small size aneurysms, particularly for anterior circulation aneurysms, is significantly benign than previously believed, and size, location and previous bleeding were the main factors associated with rupture risks. In other previous studies of risk factors, not only aneurysmal diameter, location, and prior SAH but also hypertension, female gender, and smoking were reported as important risk factors.^5)6)15) On the other hand, there remains no controversy about the high bleeding risks of giant unruptured aneurysms. Although our over all results of coil embolization for unruptured aneurysms were relatively good with compatible mortality rate (3.8%) and no morbidity, large number of small UIAs (< 10 mm) were included in preventive coil treatment. If the ISUIA data can be generalized, many of small aneurysms of our series, particularly for anterior circulation aneurysms, can be managed by observation only.¹³⁾ Nevertheless, indications of repair for small sized anterior circulation UIAs have to be made carefully and further investigations is necessary.
   Due to the less invasive aspects of endovascular coiling and new development and improvement in this techniques every season, proportions of coling in the aneurysmal treatments continue to expand. While both treatments, clipping and coiling, has been done by vascular neurosurgeons in our department over 8 years, same trend was noticed in our series, particularly in unruptured aneurysms (Fig. 2). However, sufficient data comparing the clipping and coiling in the treatments of unruptured aneurysms are not available, although some randomised data about the ruptured aneurysms has been published. One of the best available data comparing clipping and coiling is from the prospective but non-randomised arm of ISUIA-Part 2. Surgical clipping had combined morbidity and mortality at 1 year of 12.2% versus 9,5% for coiling, however, aneurysmal obliteration was complete in only 51% of cases.¹²⁾ Important concerning about endovascular aneurysmal coiling is limitation of complete obliteration and recanalization. And, although endovascular coiling has been shown effective in prevention of rebleeding after SAH, same effect in unruptured aneurysms is questionable since durability of treatment needs a follow-up of several decades. In a Brilstra's prospective study comparing the quality of life and functional health after treatment of UIAs between surgical clipping and coil embolization, operation has considerable impact on functional health and quality of life, however coil embolization does not.¹⁾ Unruptured giant aneurysms are indicated treatment as they have relatively high bleeding risks. Management of giant or complex aneurysms is generally very challenging with any single method, but combined endovascular and microsurgical management of giant or complex aneurysms are often very useful and successful.¹¹⁾
   Between 3.6 and 6% of the population harbour an unruptured intracranial aneurysm.¹⁴⁾ Depending on what investigating methods was taken, such as autopsy or MRA, the detection rate can vary widely. Recent improvements of non-invasive imaging technique, like magnetic resonance angiography (MRA) or multi-slice computed tomography angiography (MDCTA), caused increase in detection of UIAs. Although this techniques make diagnosis of UIAs possible without conventional DSA in many cases, the quality of data still has some limitation and insufficient in detecting small aneurysms. As non-invasive techniques improves rapidly and brain examinations using these imaging techniques will expand as an alternatives to DSA, increased detection of UIAs is expected.

Conclusions

   Thanks to the improvement of non-invasive imaging techniques and establishment of endovascular coil techniques as an alternatives to surgical clipping, both numbers, absolute number of detected UIAs and number of UIAs treated by coil, continue to increase in recent years. The data of ISUIA presented improved understanding on a controversial point of natural history of UIAs and risks associated with surgical repair of UIAs. Since the bleeding risks of small sized, anterior circulation UIAs has much benign than previously thought, indications of treatment for this particular group of aneurysms have to be made carefully. And also, based on the important risk factors of UIAs, a practically useful guideline for the treatment of UIAs is need to be made.

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