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.
4.1 Endovascular coiling
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.
4.2 Microsurgical clipping
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
4.3 Endovascular coiling (EC) versus microsurgical clipping (MC)
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.