DOI: https://doi.org/10.21203/rs.3.rs-1822353/v1
Extremely small intracranial aneurysms (ESIAs) with a diameter no more than 2 mm are great challenges in neurosurgery. This study analyzed the complications, angiographic results, and clinical outcomes of patients with ESIAs undergoing endovascular coiling (EC) and microsurgical clipping (MC) and aim to determine which treatment is more beneficial for ESIAs.
Data of patients with ESIAs treated with EC or MC were retrospectively analyzed from February 2013 to December 2020 in the neurosurgical department of our hospital. Follow-up imaging included computed tomography angiography or digital subtraction angiography, and patient recovery was evaluated using the Glasgow Outcome Scale (GOS). The primary outcome was GOS 6 months later. The secondary outcomes included GOS at discharge, aneurysm occlusion rate 6 months after treatment, and postoperative complications such as cerebral infarction, hydrocephalus, pulmonary infection, postoperative rebleeding, hepatic or renal insufficiency, and electrolyte disturbance.
A total of 88 patients were included in this study, among which 48 patients were treated with EC and 40 patients were treated with MC. There was no difference in complications between the two groups, and the hospitalization time of EC group was shorter than that of MC group. But immediate postoperative angiography results showed that the occlusion rate of EC group was lower than MC group at discharge and 6 months later. There was no difference in GOS scores between the two groups at discharge and 6-month follow-up.
EC and MC treatments were alternative management for patients with ESIAs.
ESIAs is defined as an intracranial aneurysm with a maximum diameter of no more than 2 mm1. In the past, ESIA has rarely been studied because of its low detection rate. With the emergence and popularization of three-dimensional digital subtraction angiography (3D-DSA), the detection rate of ESIA has significantly increased. The International Subarachnoid Aneurysm Trial (ISAT) has suggested that endovascular coiling (EC) has better outcomes than that microsurgical clipping (MC) in patients who underwent both EC and MC2. However, since ISAT included all aneurysms, treatment for patients with ESIAs is still controversial3,4. EC treatment for ESIAs is technically difficult because of the limited space of aneurysms. MC treatment for ESIA is also difficult because the neck of the aneurysm is so small that the clip can easily slip and tear the aneurysmal neck. Occasionally, when MC is difficult, sacrificing part of the parent artery is necessary to achieve complete occlusion, which may result in stenosis or occlusion of the artery, leading to ischemic injury5. The rupture of ESIA is unpredictable, and patients with high-risk factors, such as young age, anterior communicating artery (ACoA) location, and hypertension, should be treated promptly6. In addition, recent studies have found that most ruptured aneurysms are small or very small7. Because these aneurysms have extremely small cavities and thin walls, and most of them are wide-necked aneurysms, both MC and EC treatments are very difficult. In this study, we compared the differences in aneurysm occlusion rate, complications, and short-term and long-term outcomes between the two groups to determine which treatment method is more beneficial for ESIAs.
This retrospective study was conducted from February 2013 to December 2020 at the Department of Neurosurgery. Inclusion criteria: (1) Aneurysm diameter was no more than 2 mm; (2) Written informed consent was obtained from all patients or designated proxies; (3) patients without other cerebrovascular diseases such as cerebral infarction and cerebrovascular malformation; (4) ruptured ESIA or unruptured ESIA combined other ruptured aneurysm or unruptured ESIA with severe intracranial vascular stenosis requires stent treatment8,9.
All patients underwent general anesthesia after endotracheal intubation. After successful femoral artery puncture, routine DSA of the whole cerebral blood vessel was initially performed to exclude other vascular problems and to determine the location, shape, size, and parent artery of the aneurysm. Based on the results of the 3D DSA, the appropriate surgical approach, angle, and stent were selected. A 6-F guiding catheter was placed in the distal internal carotid or vertebral artery. Following a roadmap in the working projection, the head of the stent microcatheter was placed at the distal end of the parent artery guided over the micro-guidewire in patients requiring stent-assisted embolization. Then, the microcatheter was advanced via a micro-guidewire and carefully placed in the aneurysmal cavity. According to the size and shape of the aneurysm, appropriate coils were selected to fill it with the assist of stent through semi-deployment technique. Coils with a diameter of 1.5 mm or even 1 mm were selected because of the extremely limited space of the aneurysm. The stent was fully deployed after complete coiling. A control angiography was performed to determine the extent of embolization and to assess whether the parent artery was occluded.
Pterional or interhemispheric approaches were used for operation according to the location and aneurysms. The parent artery and ESIAs were exposed. A suitable temporary clip was selected to block the parent artery temporarily. The blood vessels and nerves around the aneurysm should be carefully observed before clipping to avoid damaging important perforating vessels and nerves. We carefully applied the mini clip to the neck of aneurysm and checked whether the parent artery is narrow, and whether the aneurysm is completely occluded using fluorescence angiography. Postoperative CTA was performed to examine the parent artery and the occlusion of aneurysm. Intraoperative rupture, surgical approach, clip slippage and preoperative VP-shunt were recorded.
Complications such as intraoperative rupture, thrombosis, cerebral infarction, cerebral vasospasm, hydrocephalus, pulmonary infection, postoperative rebleeding, hepatic or renal dysfunction, electrolyte disturbance, and decompressive craniectomy were recorded before discharge. The Modified Raymond Classification10 was used to evaluate the degree of aneurysm occlusion immediately after intervention and during follow-up. Discharge and 6-month follow-up GOS scores were recorded in the EC and MC groups, respectively.
GraphPad Prism 8.02 (Inc., La Jolla, CA, USA) and SPSS 22.0 (Inc., IBM, Armonk, NY, USA) was used for statistical analysis and plotting. Data are presented as mean ± standard deviation and appropriate percentage. An unpaired t-test was used to evaluate the difference between the two groups. Counting data are represented by n (%), and the chi-square test was used to assess the relative risk. P-values of < 0.05 were considered statistically significant. The Wald χ2 test was used to determine the therapeutic effect of the procedures. The incidence and relative risk of dichotomous variables in the EC group versus the MC group were described, with a confidence interval of 95%.
A total of 88 patients were included in this study, among which 48 patients were treated with EC and 40 patients were treated with MC at the Department of Neurosurgery in our hospital from February 2013 to December 2020 (Fig. 1). No statistically significant differences in baseline characteristics were observed between the two groups. All patients were included in the final intention-to-treat analysis (Fig. 2). All data including those on sex, age, aneurysm location, size, complications, discharge, and follow-up GOS were recorded.
The baseline characteristics of the patients are summarized in Table 1 and aneurysm data are shown in supplement Table 1.
|
characteristics |
All (n = 88) |
Clipping group(n = 40) |
Endovascular group (n = 48) |
|---|---|---|---|
|
Age (years), mean ± SD |
56.1 ± 10.2 |
53.7 ± 8.9 |
58.1 ± 10.7 |
|
Sex, n (%) |
|||
|
Male |
28(31.8%) |
15(37.5%) |
13(27.1%) |
|
Female |
60(68.2%) |
25(62.5%) |
35(72.9%) |
|
Comorbidities, n (%) |
|||
|
Smoking |
24(27.3%) |
10(25%) |
14(29.2%) |
|
Hypertension |
48(54.5%) |
21(52.3%) |
27(56.3%) |
|
Presentation |
|||
|
Rupture (%) |
69(78.4%) |
35(87.5%) |
34(70.8%) |
|
Unruptured (%) |
23(26.1%) |
5(12.5%) |
18(29.2%) |
|
H-H grade |
|||
|
0 |
5 |
14 |
|
|
1 |
2 |
8 |
|
|
2 |
19 |
9 |
|
|
3 |
9 |
14 |
|
|
4 |
4 |
2 |
|
|
5 |
1 |
1 |
|
|
Fisher grade |
|||
|
0 |
5 |
14 |
|
|
1 |
9 |
4 |
|
|
2 |
4 |
17 |
|
|
3 |
9 |
7 |
|
|
4 |
13 |
6 |
All patients were successfully treated with EC or MCs. In the EC group, there were 30 cases of stent-assisted embolization, 15 cases of simple coil embolization, and 3 cases of double microcatheter embolization. A total of 44 cases with Raymond grade I and four cases with Raymond grade II were confirmed by angiography immediately after surgery. In the MC group, ESIAs were clipped successfully, including rupture of aneurysms in two patients and slippage of aneurysms in two patients. Postoperative cerebral CTA revealed complete occlusion of the aneurysm (table 2). Complications were observed in 7 cases in EC group versus 8 cases in MC group (P = 0.350) (supplement table 2 and Fig. 3B). The hospital stay in the EC group (10.16 ± 4.5 days) was significantly less than that of the MC group (12.50 ± 4.01 days) (Fig. 3A). Typical cases treated with EC and MC are shown in supplement Figs. 1 and supplement Figs. 2, respectively.
|
characteristics |
frequency |
|---|---|
|
EC |
|
|
Treatment methods, n (%) |
|
|
Single microcatheter |
15(31.3%) |
|
Double microcatheter |
3(6.2%) |
|
Stenting with coiling |
30(62.5%) |
|
Stent type, n (%) |
|
|
LVIS |
22(73.4%) |
|
Enterprise |
1(3.3%) |
|
Neuroform |
1(3.3%) |
|
Solitaire |
3(10.0%) |
|
Leo baby |
3(10.0%) |
|
MC |
|
|
Intraoperative variables |
|
|
Intraoperative rupture, n (%) |
2(5%) |
|
clip slippage |
2(5%) |
|
Preoperative VP-Shunt insertion, n (%) |
5(12.5%) |
|
Surgery Approach |
|
|
pterional, n (%) |
38(95%) |
|
Coronary, n (%) |
1(2.5%) |
|
Supraorbital lateral, n (%) |
1(2.5%) |
| Abbreviations: endovascular coiling, MC; microsurgery clipping, MC. | |
All patients in the EC group were followed up with DSA and showed good recovery. Angiography showed the rate of aneurysmal occlusion with Raymond Scale grade I in 46 (93.55%) patients and grade II in 2 (6.45%) patients in the EC group with 6 months’ follow-up. Cerebral CTA examination was performed in the MC group, and no recurrence was observed. GOS assessment was performed at discharge and 6 months later in all patients. Compared to patients in the MC (75%, 30/40) group, a higher percentage of patients in the EC (83.3%, 40/48) group had good recovery (GOS 5) at discharge, but the difference was not statistically significant (P = 0.33, 95% CI 0.70–1.12). Six months later, the recovery rates in the EC and MC groups increased to 93.75% (45/48) and 87.5% (35/40), respectively (Fig. 4A). Some patients with GOS scores were not 5 eventually changed to 5 at subsequent follow-up, including 6 patients in the EC group and 6 patients in the MC group; however, 1 patient died. Moreover, 1 patient with GOS 5 scores changed to 4 in each group (Fig. 4B and 4C). Subgroup analyses for a good outcome (GOS 5) showed no effect of age, sex, hypertension, smoking, aneurysm location, and good or poor clinical condition (Hunt–Hess grades and Fisher grades) at discharge (Fig. 5A) and 6 months follow-up (Fig. 5B) in the MC groups and EC group.
In our study, an ESIA was defined as an aneurysm with a maximum diameter no more than 2 mm, which differs from the definition of traditional very small intracranial aneurysms (VSIAs) with diameters of less than 3 mm1,11,12. Previous studies on small intracranial aneurysms mainly focused on aneurysms not more than 3 mm and found that both EC and MC treatment can achieve good results in VSIAs13,14. Compared with VSIAs, ESIAs have smaller aneurysm spaces. EC treatment is more likely to cause rupture, whereas MC treatment is more likely to cause clip slippage. Which management is the optimal treatment for the patient with ESIAs is still controversial. It was reported that small intracranial aneurysms with diameter less than 7 mm were reported to have a low incidence of rupture15. However, some studies reported that the rupture rate of small intracranial aneurysms was higher than expected. When patients have high risk factors for rupture, such as young age and aneurysms located in the ACoA, accompanied by hypertension and smoking, surgical treatment is reasonable and necessary6,16. For unruptured ESIAs with other ruptured IA or with severe intracranial and extracranial vascular stenosis requiring stent treatment, we performed the treatment together with ruptured IA and/or stenosis. MC and EC are both challenging to treat ESIAs, and it remains to be seen which treatment is better. Therefore, the complications and postoperative recovery of 48 cases with EC and 40 cases with MC treatment in our hospital were compared.
The rapid advances in endovascular manufacturing technologies, such as softer, smaller coils and stents with denser mesh, make embolization of tiny aneurysms safer17. Endovascular treatment can be divided into pure coil embolization and stent-assisted coil embolization. For narrow-necked ESIAs, pure coil embolization is sufficient, whereas for wide-necked ESIAs, stent-assisted embolization is required to prevent coil prolapse. Several kinds of stents are available in the embolization of aneurysm, including Neuroform EZ and Atlas, LEO (light-emitting diode), low-profile visualized intraluminal support (LVIS), Solitaire, and Enterprise stents. Due to the small space in the ESIAs, the suitable coils can be used during the operation are with diameter of 1.5mm or 1 mm, thus the mesh of the stent should be less than 1 mm otherwise the coil has risk of escape from the mesh. Therefore, it is necessary to select an appropriate stent for ESIAs. The LVIS and LEO stents have high metal coverage (up to 23%) because of their mesh less than 1 mm, and it was reported that these stents can even be used as a flow diverter1. Moreover, LVIS Junior, LEO Baby stents are the best choices for wide-necked aneurysms with a parent artery diameter < 2 mm due to their small size6. Therefore, LVIS, LVIS Junior, LEO and LEO Baby stents were mostly used to assist the embolization of wide-necked ESIAs in this study. In our study, most of the ESIAs were treated with the assistance of these stent, except 5 patients with enterprise in the early period.
Intraoperative aneurysm rupture has been a common and serious complication of EC treatment in the past. It has been reported that during the treatment of 422 aneurysms, 35 patients (8.3%) experienced intraoperative aneurysm rupture18. Moreover, it has been reported that the intraoperative rupture rate of VSIAs is more than two times higher (7.7%) than that of larger aneurysms16. However, recent studies, including our previous study, showed a lower rate of intraprocedural rupture than previous studies1,12,19. In our study, no intraoperative rupture occurred in 48 patients undergoing EC treatment, which we believe is related to the following factors. First, under the dual detector, the good plasticity of the microcatheter can stabilize in the center of the aneurysm cavity and avoid puncture of the aneurysmal wall with skilled microcatheter and wire technique. Second, the coil with a diameter less than or equal to the diameter of the aneurysm was selected to reduce the pressure of the coil on the aneurysm wall. Third, the semi-deployment technique avoids cage the microcatheter between aneurysm sac and stent, which reduces the risk of rupture during embolization.
In addition, thrombosis is another common complication of endovascular treatment, especially in patients undergoing stent-assisted embolization. The incidence of intra-procedural thrombosis during stent-assisted embolization for ruptured intracranial aneurysms was 8.1%20 to 11.2%,21 which is lower than that of VSIAs22. However, in our study, anticoagulant therapy was fully performed before, during, and after the operation, and external saline with high pressure was infused in the microcatheters continuously during the operation to prevent catheter thrombosis. Thus, no thrombotic events occurred in our series.
The proportion of recurrent aneurysms treated with EC ranged from 4–20%. Aneurysm recurrence is highly dependent on the location, size, neck, and incomplete embolization of the aneurysm13. ESIAs treated with pure coils achieved good stability and embolic compactness in aneurysms with narrow neck, meanwhile, stent-assisted embolization was mainly applicable to wide-necked ESIAs. It not only alters the flow dynamics in the parent vessel, but also provides a scaffold for the growth of endothelial cells23. Interesting, the rate of recurrence in ESIAs is lower even aneurysms were embolized with Raymond grad II, which showed us there are maybe some differences about the rate of embolization during the operation between ESIAs and bigger aneurysms.
MC treatment, which includes a single clip24, double clip11,14 and cotton-assisted5 surgical clipping techniques, remains the primary option for the treatment of ESIAs when EC fails or combined with hematoma.. Because of the small size of ESIA, MC treatment is prone to clip slippage because of the small cavity of the aneurysm. Therefore, double-clip technology or post-wrap clamping has been adopted in MC treatment for ESIAs to avoid clip slippage in recent years. In this study, the total occlusion rate of the MC was 100%. None of the patients had remnant aneurysms or rebleeding. Two (2.3%) incidences of clip slippage were noted in two patients in our study, which has been reported previously with different frequencies in different series.14,24 Intraoperative rupture is also a common complication of MC. Several factors, such as the location of the aneurysm, blood-blister aneurysm, intraoperative blood pressure fluctuation, and surgical experience of the surgeon, influence the rate of intraoperative rupture.25,26 In order to avoid complications, the parent artery and aneurysm should be exposed completely, and the proximal and distal parent arteries be blocked with temporary clips before clipping the aneurysm. Moreover, the operative site should be carefully checked to ensure whether the aneurysm was clipped completely and the perforating artery was not occluded. In our study, two patients experienced intraoperative aneurysm rupture and were completely clipped after temporary occlusion of the parent artery. Complications such as ischemia and rebleeding are also reported after MC. Bruneau et al. reported that the total occlusion rate of aneurysms was 98.2% and the mortality rate was 0%, only 2.7% patients had persistent neurological complications.24 Grasso reported that surgery-related ischemia occurred in 15% of patients, and bleeding occurred in 13.2% of patients.27 In our study, one patient (2.86%) died of severe preoperative cerebral hemorrhage, three (8.55%) patients developed postoperative cerebral infarction, and none showed postoperative rebleeding. In addition, complications that seem not very serious may have a certain impact on the patients’ prognosis if not been properly managed. In our study, three patients with ESIA of anterior communication artery had electrolyte disturbance after surgery, which may be caused by influence of the hypothalamic perforating arteries which originating from the ACoA. In general, the hypothalamic perforating arteries are a group of two to six arterial branches that supply blood to the various regions of the hypothalamus, with 10% originating on one side of the ACoA and ending on the other side of the hypothalamic region. Symptoms such as water and electrolyte disorders, consciousness disorders, cognitive disorders, and high fever may occur if the hypothalamic perforated artery is injured during the operation.28
So far, there are no studies focused on the comparison of EC and MC treatment for ESIAs. Previous studies retrospectively analyzed the clinical outcomes of 162 patients with VSIAs treated with either EC or MC. They found a slight trend towards improvement in outcomes with EC, but no significant differences were observed.13 In addition, another study that analyzed 130 patients with ruptured ACoA aneurysms found no significant differences in complication and retreatment rates between EC and MC at discharge and at 1- and 3-year follow-up periods.29,30
Therefore, we reported on 48 patients with ESIAs treated with EC and 40 patients with ESIAs treated with MC. All unruptured ESIAs were accompanied with severe internal carotid artery stenosis, and aneurysms should be treated before stent implantation or combining with other ruptured aneurysms, ESIA was treated at the same time as responsible aneurysm treatment in the EC group. Patients with large amounts of bleeding and high risk of hydrocephalus are mostly treated with MC, so as to remove hematoma and ventriculostomy during surgery and reduce the incidence of hydrocephalus. Meanwhile, for both EC and MC are suitable, we also considered the will of the patient's family to choose EC or MC.
In our series, there was no blister-like aneurysm in this group and the mortality rates of the two groups were 1.9% for coiling and 2.5% for clipping. Our results showed that procedure-related complications, such as cerebral infarction, hydrocephalus, pulmonary infection, postoperative rebleeding, hepatic or renal insufficiency, and electrolyte disturbance, occurred in 8/40 patients who underwent MC treatment compared with 7/48 patients who underwent EC treatment for ESIAs. In the EC group, 5 patients showed subtotal embolism after surgery, but DSA results revealed complete aneurysm occlusion during follow-up. In contrast, 2 patients showed complete embolization postoperatively while follow-up angiography revealed a recurrence of the aneurysm. In the MC group, the cerebral CTA of all patients showed complete clipping of the aneurysm at discharge, and there was no recurrence of the aneurysm during follow-up. The occlusion rate in the EC group was lower than that in the MC group, but it increased during follow-up. Further study revealed that blood pressure should be controlled after operation and that the stent could provide a scaffold for endothelial vessel growth and ultimately promote aneurysm occlusion. Coincidentally, 2 recurrent patients had hypertension and poor blood pressure control. For ESIAs located in the posterior circulation, MC treatment usually requires aggressive cranial base resections with transpetrosal approaches, complete control of the proximal and distal vessels, and extensive exposure of the aneurysm, which undoubtedly increase the trauma of the brain. Comparatively, EC treatment is significantly easier and more optimal for these patients. Therefore, all posterior circulation ESIAs in this study were treated with EC, and all patients successfully underwent EC treatment to achieve aneurysm embolism. MC treatment was feasible for patients who failed EC treatment or had blood blister-like aneurysms.
Our study has several limitations. First, it was a retrospective study and did not include a completely randomized control group. For example, we chose EC for the treatment of posterior circulation aneurysms, and we chose MC treatment for most of the aneurysms in the middle cerebral artery. However, no significant differences in sex, age, clinical grade, Fisher grade, or treatment timing were observed between the two groups. Second, this was a single-center study, and the results are only from our center, which may be different from those in other centers; whereas, our results are consistent with the current trend of aneurysm treatment results. Meanwhile, the MC group was followed up with CTA, whose results may not be accurate enough to evaluate aneurysm recurrence. Finally, follow-up results of CTA and DSA were only 81.5%, which may not be applicable to all patients.
Patients with ESIAs were suitable for both EC and MC treatments because no significant difference was observed in the outcome during discharge and follow-up.
The study was approved by the Ethics Committee of our hospital (WDRY2021-K070).
None
Qi Tian and Yujia Guo wrote the original draft, Shou-Meng Han, Junhui Chen and Jianfeng Wang collect data. Cheng-Li Liu and Gang Deng and Shenqi Zhang count and analyze data, Junmin Wang, Daofeng Tian and Qianxue Chen drew the figures and tables. Mingchang Li reviewed and revised articles for final versions.
This work was supported by the National Natural Science Foundation of China (grant/award no. 81971870, 82172173).
None