Introduction

The elderly population has increased in Korean society and is expected to continue to increase over the ensuring years at a more rapid rate. As the proportion of elderly in the general population increases, this age bracket will continue to account for increasingly more significant proportion of the patients with intracranial aneurysms. Until recently, the standard method of treatment for intracranial aneurysms was craniotomy and microsurgical clipping.3)9)17)19)21)35)36) But, elderly patients with intracranial aneurysms have a greater risk of poor outcomes18)29) than younger patients undergoing microsurgical treatment (MST). Older age, combined with a higher frequency of co- morbidities, poorer clinical grades on admission12)13)20) and less active management, makes many of these patients poor surgical candidates. In general, patients >50 years of age would have more difficult time tolerating craniotomy and clipping of intracranial aneurysms than younger patients. In 1991, endovascular coiling for intracranial aneurysms was introduced as an alternative to microsurgical clipping. Since 1995 endovascular treatment (EVT) has been widely adopted as a competitive technique for the treatment of intracranial aneurysms.24)25) Because of the lower risk of rebleeding without the need for craniotomy, thereby reducing surgical trauma, EVT has been welcomed as a promising alternative to MST, especially in elderly patients with poor grade aneurysms.31) In 2002 the International Subarachnoid Aneurysm Trial (ISAT) suggested that the outcome in terms of survival, without disability, after 1 year of treatment is significantly better following endovascular coiling in all ages.24) Many studies have reported successful EVT of intracranial aneurysms with minimal complications in the elderly.2)15)22)26)30)32) However, in 2009, the 5-year follow-up results of the ISAT were published, demonstrating that the aforementioned benefits observed after 1 year of treatment appears to have vanished and no significant difference in disability or mortality remains between the two treatment modalities.23) Furthermore, in spite of the low rate of medium term rebleeding rates in both groups, rebleeding was nonetheless slightly more common in the EVT group. In addition, there still remains controversy on how to choose the best treatment for intracranial aneurysms between EVT and MST, especially in elderly patients. We present our experience on EVT and MST in 37 and 47 elderly patients (≥65 years of age), respectively.

Patients and Methods

Between March 2007 and June 2010, 101 patients ≥ 65 years of age were hospitalized for ruptured or unruptured intracranial aneurysms at our hospital. Seventeen patients with incomplete data, those not available for follow-up, and those with multiple cerebral aneurysms, which were discovered when both modalities were applied for the same patient, were excluded. In all circumstances, both the neuroradiologist and neurosurgeon jointly assessed the aneurysm primarily for complete occlusion. The standard indication for EVT in our hospital includes medically unstable conditions (cardiac and pulmonary disease), surgical contraindications because of difficult locations or the configuration of aneurysms, recurrent or residual aneurysms after unsuccessful surgery and refusal of surgery. However, the perfect standard for choosing between EVT and MST does not seem to exist and both treatment methods were determined on the basis of considerations for the shape of aneurysms, the width of the neck, the preference of the neuroradiologist and neurosurgeon, patient choices and the patient health status. The aneurysms were treated in 37 cases via EVT (group I) by the same neuroradiologist with coils and in 47 cases via MST (group II) by the same neurosurgeon. In group I, 20 patients (54.05%) had unruptured aneurysms, while 17 patients (45.95%) had ruptured aneurysms. In group II, 24 patients (51.06%) had unruptured aneurysms, while 23 patients (48.94%) had ruptured aneurysms (Table 1). The intracranial aneurysms were diagnosed by cerebral angiography. Subarachnoid hemorrhage (SAH) was confirmed by CT scan or lumbar puncture. Clinical assessment was made on admission with the Hunt and Hess grade (HHG)11) and on discharge with the Glasgow Outcome Scale (GOS).14)

Student’s t-test, a chi-square test and logistic regression analysis were performed for statistical evaluation. A probability value of 0.05 was used as the level of significance.

1. Group I

There was marked female predominance (32 women [86.49%] vs. 5 men [13.51%]) with an age range of 64-82 years (mean, 70.22 years). There were 8 patients (21.62%) with low-grade aneurysms (HHG < III), with the exception of those with unruptured aneurysms (20 [54.05%]), while there were 9 patients (24.32%) with high-grade aneurysms (HHG > III). The main associated risk factors and pre-existing illnesses included arterial hypertension, cardiac disorders and diabetes. Arterial hypertension was present in 12 patients (48%), cardiac disorders in 5 patients (20%) and diabetes in 4 patients (16%). Other factors were smoking and gastrointestinal disorders. Thirty-three aneurysms (89.19%) were in the anterior circulation and 4 aneurysms (10.81%) were in the posterior circulation. The size of aneurysms was < 10 mm in 33 cases (89.19%) and in the range of 10~15 mm in 4 cases (10.81%; Table 1).

For patients with aneurysms > 10 mm, there were equal frequencies of good and poor outcomes (2 patients each; Table 2). Complete angiographic occlusion was achieved in 33 aneurysms (89.19%). A neck remnant or incomplete occlusion recorded in 4 aneurysms (10.81%; Table 3).

2. Group II

There was also marked female predominance (38 women [80.85%] vs. 9 men [19.15%]) with an age range of 65-81 years (mean, 70.45 years). There were 12 patients (25.53%) with low-grade (HHG < III), with the exception of those with unruptured aneurysms (24 patients [51.06%]), while there were 11 patients (23.41%) with high-grade aneurysms (HHG > III). Arterial hypertension was the main risk factor (20 patients [54%]), followed by smoking and cardiac disorders, 6 patients (16%) and 4 patients (11%),

respectively. Other factors were diabetes, gastrointestinal disorders, alcohol consumption and obesity.In all cases, aneurysms were located in the anterior circulation. The size of aneurysms was < 10 mm in 39 patients (82.98%) and in the range of 10~15 mm in 6 patients (12.77%) along with large aneurysms (>15 mm) in 2 cases (4.26%; Table 1).

Five of eight (62.5%) patients with aneurysms > 10 mm in size had poor outcomes (Table 2). We confirmed complete clipping of the aneurysms by performing 3-dimensional CT angiography in 45 patients (95.74%) and partial clipping or wrapping of aneurysms in 2 cases (4.26%; Table 3).

Results

1. Peri-procedural complications with coiling

Six complications occurred (16.22%) and 2 of which were medical complications (Table 4). Of the three cases of thromboemboli, one occurred in an unruptured aneurysm in the left anterior cerebral artery. After complete endovascular obliteration of the aneurysm, the patient complained of right side motor weakness. The MRI image showed acute ischemic changes in the left middle cerebral artery territory. Although heparinization and hydration were attempted initially, the patient continued to have mild right-side hemiparesis. Two patients, who had thromboemboli arising from the treatment of unruptured aneurysms, had delayed ischemic strokes resulting in hemiparesis. Aneurysm rupture occurred in a patient who initially presented with a HHG I, 13 mm ruptured aneurysm in the right middle cerebral artery. Although complete endovascular obliteration of the aneurysm was achieved, a post-coiling CT scan showed an intracerebral and subdural hemorrhage which needed an emergency craniectomy and hematoma removal. After treatment, the patient recovered and was discharged with GOS 3. Pulmonary complications occurred in two patients during post-coiling care. The pneumonic process followed by pulmonary edema was treated successfully with medical consultation.

2. Post-surgical complications with microsurgery

Surgery-related complications were noted in 8 patients (17.02%) treated with clip placement (Table 4). Pulmonary complications, particularly pulmonary edema and pneumonia, were more prevalent in the patients subjected to MST. Five patients who suffered pulmonary complications were treated successfully. These complications are well-known in patients with prolonged artificial ventilation due to an increased length of stay in an intensive care unit and prolonged bedrest. The seizure attack occurred in two patients during post-operative care. It is reasonable to believe that the craniotomy, aneurysm dissection and the use of self-retaining brain retractors to some extent resulted in the development of epilepsy. Meningitis (1 patient) also occurred in the MST group. This com- plication responded to conservative therapy with appropriate antibiotics and excellent recovery was shown.

3. Clinical outcome

There was a favorable outcome (GOS, 4-5) in 89.19% of the patients in group I and in 82.98% in group II (Table 5). An analysis of clinical outcome in relation to clinical grade at the time of admission showed an important difference between the two groups (Table 6). In group I, 100% (20/20) of the patients with unruptured aneurysms and 87% (7/8) of the patients with low-grade (HHG < III) ruptured aneurysms achieved favorable outcomes, whereas 33% (3/9) of the patients with high-grade (HHG > III) ruptured aneurysms either died or displayed very poor outcomes (GOS, 1-3). In group II, 95.83% (23/24) of the patients with unruptured aneurysms and 83.33% (10/12) of the patients with low-grade (HHG < III) ruptured aneurysms showed favorable outcomes. Poor outcome (GOS, 1-3) was observed in 5 of 11 patients (45.5%) with high-grade (HHG > III) ruptured aneurysms. In treatment of unruptured aneurysms, significantly more favorable outcomes (GOS, 4-5) were noted with group I than group II; favorable outcomes were observed in all patients (100%) in group I and 23 of 24 patients (95.83%) in group II (Fig 1). Similarly, in treatment of ruptured aneurysms, group I achieved more favorable outcomes than group II; favorable outcomes occurred in

76.47% (13/17) vs. 69.57% (16/23) of unruptured and ruptured aneurysms, respectively (Fig. 2).

4. Statistical analysis

With the presumption that gender, existing illnesses, aneurysm location, aneurysm size, HHG and treatment modality (EVT vs. MST) at the time of admission can influence the GOS score, the p values of each variable were evaluated. The pvalues of each variable were computed by calculating the averages of age, aneurysm size, HHG and GOS at the time of admission by means of Student’s t test (Table 7). In terms of the average values, although there was a slight difference in these factors, p values were the only statistically significant differences in GOS (p=0.046). When evaluation was made with chi-square tests by considering whether or not there was existing disorders in each of the patients in the EVT and MST groups, aneurysm size and HHG were significantly different (p=0.000 and p=0.001, respectively). Based on multivariate analysis by log regression test, the aneurysm size was significant (OR=9.293; 95% CI, 1.684-51.281; p=0.011). In addition, the HHG was also significant based on multivariate analysis (OR=6.375; 95% CI, 1.152-35.271; p=0.034). However, among the factors that affect clinical outcome, treatment modality (EVT vs. MST) was not statistically significant (Table 8).

Discussion

Many previous studies have compared the clinical outcomes of patients with intracranial aneurysms who were treated endovascularly or surgically.1)4-8)10)24)25)27)28)34) Vanninen et al.35) demonstrated that the clinical outcome at 3 months was comparable between the EVT and MST groups in a prospective, randomized study of 109 patients with acute subarachnoid hemorrhage (SAH) caused by ruptured aneurysms. For unruptured aneurysms, Johnston et al.16) reported that adverse outcome is significantly more common in surgical cases (18.5%) compared with endovascular cases (10.6%) and the difference was not altered even after making adjustments for age, gender, race, transfer admission, emergency department admission and number of years of treatment. They also indicated a higher hospital mortality rate for surgical cases (2.3%) in comparison to coiling (0.4%). On the basis of their results, they concluded that EVT resulted in fewer adverse outcomes than MST for unruptured aneurysms. Taha et al.33) indicated that periprocedural technical complications associated with EVT was lower than surgery-related complications associated with MST for both ruptured and unruptured cerebral aneurysms.

There were also some limitations of EVT compared with MST in treatment of intracranial aneurysms. It is difficult to attempt EVT and succeed even if EVT is attempted in the cases, including pre-aneurysmal lesions, severe tortuosity of vessels, aneurysms with a wide neck, aneurysms with a branch arising from the sac and when multi-directional fusiform aneurysms are at one location. Weakness of EVT includes the lack of

re-assurance of direct visual inspection in the aneurysm and its obliteration, the lack of long-term research data on the durable efficacy and the low incidence of total aneurysm occlusion resulting in recanalization with subsequent aneurysm rebleeding.

However, there are relatively few studies that have compared EVT and MST in the elderly. The optimal management of intracranial aneurysms in the elderly remains controversial. We investigated the clinical characteristics and outcome in EVT and MST of intracranial aneurysms implemented on elderly patients > 65 of ages.

When the GOS score, which was independent of rupture, was evaluated at the time of discharge, there was a trend of acquiring a good GOS score when the HHG was good at the time of admission in both EVT and MST groups. On the other hand, when the HHG is bad at the time of admission, the GOS score tended to be bad, thereby illustrating that HHG at the time of admission influenced the GOS score. Moreover, there was a trend that the GOS score was worse when the aneurysms size was > 10 mm in comparison to < 10 mm. It can be concluded that HHG and aneurysm size (<10 mm or ≥10 mm) at the time of admission is a significant factor that affects the GOS (Table 8).

In the 2 groups that underwent EVT and MST, average values of GOS score by Student t-test were significantly different (4.54 [EVT] and 4.13 [MST], respectively, p=0.046; Table 7). However, they were not statistically significant based on univariate and multivariate analyses (Table 8).

If EVT or MST is not statistically significant factor on the GOS score, then it can be deemed less invasive EVT with less post-procedural complications is a treatment method that can certainly be considered in treatment of intracranial aneurysms in case of the elderly patient group. In addition, it would be able to overcome the limitations in the case of the elderly patient group that there is a lack of long-term research data on the durable efficacy and it has a higher

recurrence rate than MST. Because the lifespan of elderly patients is relatively shorter, the long-term usefulness of endovascular obliteration may be less important than in younger patients.

Conclusion

In the EVT and MST performed on elderly patients with ruptured and unruptured aneurysms in our hospital, the average value of the GOS score for the EVT group was significantly higher than the MST group. However, the GOS scores were not statistically different between the two groups. Because the two treatment methods do not differ statistically, with respect to the GOS score, then the less invasive EVT with less post-procedural complications in elderly patients can be considered with priority. It is anticipated that more favorable treatment results could be obtained in the future as endovascular techniques are being advanced even further. In this study, although the clinical grade at the time of discharge was evaluated in terms of GOS scores, the fact that long-term clinical follow-up was not made, and this is a limitation of this study, along with the necessity for long-term angiographic follow-up. In order to enhance the validity of our conclusion, it is believed that longer term angiographic follow-up in a larger number of cases will be needed.

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