Abstract
The long-term efficacy of clipping unruptured intracranial aneurysms via various keyhole mini-craniotomy procedures was evaluated. A retrospective review was conducted on 350 unruptured intracranial aneurysms (6.1 ± 1.9 mm) in 330 patients (218 women and 112 men, mean age 62 ± 10 years) located in the anterior circulation and clipped via various keyhole mini-craniotomy procedures between July 2005 and December 2023. modified Rankin Scale and Mini-Mental State Examination were evaluated. Anxiety and depression were assessed using the Beck Depression Inventory and the Hamilton Rating Scale for Depression. The state of clipping was assessed by computed tomography angiography at 1 year and at intervals of a few years. The mean size of the craniotomy was 26.5 ± 3.4 mm and the complete neck clipping rate was 96.9%. The mean postoperative hospitalization was 2.7 ± 3.6 days. Two patients (0.6%) experienced symptomatic lacunar infarctions. Surgical morbidity (modified Rankin Scale >2 or Mini-Mental State Examination <24) at 3 months, 1 year, and at the last examination (mean 6.6 ± 4.4 years) was 0.9%, 1.5%, and 1.8%, respectively. Neither neurological state nor cognitive function changed significantly during the follow-up period. Anxiety and depression states improved significantly at 3 months after surgery. During radiological follow up (mean 7.1 ± 4.6 years, range 1-19 years), the rates of regrowth of aneurysm remnant, recurrence, retreatment, and rupture were 18.1% (1.6%/year), 0.9% (0.1%/year), 0.9% (0.1%/year), and 0.3% (0.04%/year), respectively. Our study confirmed that keyhole clipping of unruptured intracranial aneurysm had low morbidity, early recovery in anxiety and depression, and very low aneurysm recurrence and retreatment rates, indicating that this modality is substantially curative.
Keywords: unruptured aneurysm, clipping, keyhole surgery
Introduction
Endovascular treatment for unruptured intracranial aneurysm (UIA) has recently become more common than open clipping surgery, especially with the continuous development of more advanced devices and techniques.1,2) However, direct clipping surgery for UIA continues to have several benefits such as a higher complete aneurysm obliteration rate, longer treatment durability, and a lower retreatment rate compared to endovascular treatment.3) Open clipping surgery for UIA, however, also has disadvantages, including a higher postoperative complication rate, longer hospitalization related to its invasiveness, and cosmetic problems. Modern technologies such as three-dimensional (3D) reconstruction imaging of the anatomy and aneurysm location now allow individualized planning of the keyhole approach for each patient.4-6) The keyhole approach can minimize tissue disruption and optimize the surgical outcome.5-8)
We have performed clipping surgeries via various keyhole mini-craniotomies for subsets of UIAs in the anterior circulation to maintain some advantages and resolve the disadvantages of clipping since 2005. This overview describes the benefits of keyhole clipping of UIA based on our personal experience of 350 cases over 20 years, and clarifies the best candidates for keyhole clipping in various UIA locations as alternatives to endovascular treatment. Patient cognitive and psychological conditions were evaluated and the reduced invasiveness of keyhole clipping was verified. Computed tomography angiography (CTA) was used to follow up the state of the clipping to confirm long-term durability and very low recurrence and retreatment rates. We conclude that subsets of UIAs are definitely favored for keyhole clipping, and complete neck clipping is unlikely to require extensive follow-up imaging, which tends to reduce patient anxiety and improve the quality of life.
Materials and Methods
Patients
A total of 708 UIAs were treated by surgical clipping in our institutions between July 2005 and December 2023, of which 350 aneurysms in 330 patients (218 women and 112 men; mean age 62 ± 10 years, range 33-83 years) were clipped using the supraorbital keyhole, pterional keyhole, sphenoid ridge keyhole, or unilateral interhemispheric keyhole approaches by the senior surgeon (KM). The UIAs were initially identified by neuroimaging performed for subarachnoid hemorrhage (SAH) caused by other aneurysms in 9 patients, symptomatic oculomotor nerve palsy in 2, unrelated symptoms such as headache and vertigo in 176, health examination with magnetic resonance imaging (MRI) in 91, cerebral strokes in 26, and other reasons in 26. We excluded patients with neurological deficits except for oculomotor nerve palsy caused by aneurysmal compression and those with impaired cognitive function (Mini-Mental State Examination [MMSE] <24).
The institutional ethics committee of our facilities approved the retrospective study protocol, and written informed consent was obtained from all patients (Tokyo General Hospital: No-24-18, Juntendo University Shizuoka Hospital: C24-0159-S01, National Defense Medical College: 2439).
Aneurysms, surgical indications, preoperative simulation, and types of keyhole mini-craniotomy
All UIAs were located in the anterior circulation, and were simple aneurysms with a diameter of less than 10 mm. The good and poor candidates for clipping at each location have been described elsewhere but are summarized in Table 1. Patients underwent CTA, and the 3D images of the aneurysm and skull were merged into single 3D image using Ziostation 2.4 software (Ziosoft, Inc., Tokyo, Japan) for surgical simulation. The optimal location and size of the keyhole were then determined. The approaches for 196 middle cerebral artery (MCA) aneurysms were either the pterional (160) or sphenoid ridge keyhole (36) approaches. 80 anterior cerebral artery (ACA) aneurysms (79 anterior communicating artery [AcomA] aneurysms, 1 A1 aneurysm) were treated using the supraorbital keyhole approach. 73 internal carotid artery (ICA) aneurysms (41 posterior communicating artery [PcomA] aneurysms, 23 anterior choroidal artery [AchoA] aneurysms, 8 ICA paraclinoid aneurysms, 1 ICA top aneurysm) were also treated using the supraorbital keyhole approach, and 1 ACA genu aneurysm was treated using the unilateral interhemispheric keyhole approach. The details of the surgical technique for each keyhole approach are described elsewhere. Briefly, the supraorbital keyhole approach is a combination of an eyebrow skin incision and supraorbital mini-craniotomy.8,9) The pterional keyhole approach is a combination of an outer canthal skin incision and pterional mini-craniotomy.6) The sphenoid ridge keyhole approach is a combination of a sideburn skin incision and sphenoid ridge mini-craniotomy.10) The unilateral interhemispheric keyhole approach is a combination of a straight transverse midforehead skin incision and midline frontal mini-craniotomy (Figure S1).11)
Table 1.
Good and Poor Indications for Keyhole Clipping for Anterior Circulation Aneurysm
| Location of Aneurysm | Good Indication for Keyhole Clipping | Poor Indication for Keyhole Clipping |
|---|---|---|
| MCA | Lateral projecting MCA bifurcation aneurysm | Short M1 aneurysm M1 aneurysm Posterior projecting aneurysm |
| ACA | Anterior or inferior projecting AcomA aneurysm Anterior projecting A1 aneurysm |
Posterior projecting AcomA aneurysm High-positioned AcomA aneurysm |
| ICA | Lateral projecting PcomA aneurysm Lateral projecting AchoA aneurysm Anterior projecting ICA top aneurysm |
Retro-carotid ICA aneurysm Low lying ICA Highly perforated involved aneurysm |
ACA, anterior cerebral artery; AchoA, anterior choroidal artery; AcomA, anterior communicating artery; ICA, internal carotid artery; MCA, middle cerebral artery; PcomA, posterior communicating artery
Clinical and radiological follow-up
Neurological status was evaluated using the modified Rankin Scale (mRS) and MMSE, a few days before the operation and at 3 months, 1 year, and several years after the operation. An mRS score >2 or an MMSE score <24 was defined as morbidity according to the International Study of Unruptured Intracranial Aneurysms (ISUIA).12) The level of anxiety and depression was assessed using the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D) a few days before and at 3 months after the operation.
Neuroimaging follow-up included CTA and diffusion-weighted imaging on the day after surgery, followed primarily by CTA at 1 year and several years after surgery.
Statistical analysis
The Kruskal-Wallis test or the Chi-square test was used for comparisons between the 3 groups. If a significant difference was detected, pairwise comparisons with the Mann-Whitney U test were performed between groups as post hoc tests. The Friedman test was used for comparisons across 4 time points. If a significant difference was detected, the Wilcoxon signed-rank test was used to compare the preoperative point with the 3 postoperative points to identify which points differed from the preoperative value as post hoc tests. The p < 0.05 was considered to be statistically significant. Statistical analysis was performed using SPSS Statistics 26 (IBM Corporation, Armonk, NY, USA).
Results
Surgical results
Regarding the locations of UIAs treated by keyhole clipping surgery, more than half (56%) were MCA aneurysms, followed by AcomA aneurysms (23%) and ICA aneurysms (21%). As for the types of keyholes used to clip UIAs, the pterional keyhole was used in 46%, the supraorbital keyhole in 44%, and the sphenoid ridge keyhole in 10% (Figure S2). Table 2 shows the mean aneurysm size, mean maximal size of keyhole, mean operation time, mean postoperative hospitalization, and the state of clipping in all, MCA, ACA, and ICA aneurysms. The mean aneurysm size was 6.1 ± 1.9 mm for all 350 UIAs. However, the mean size of ICA aneurysms (5.5 ± 1.8 mm) was significantly smaller than that of MCA and ACA aneurysms. The mean craniotomy size was 26.5 ± 3.4 mm, and the mean operation time was 181 ± 39 min for all UIAs. The mean craniotomy size (28.8 ± 3.5 mm) and the mean operation time (199 ± 39 min) of ACA aneurysms were significantly greater than those of MCA and ICA aneurysms. The mean postoperative hospitalization was 2.7 ± 3.6 days, and 88% of the patients were discharged within 3 days for all UIAs. The mean hospitalization of ICA aneurysms (3.2 ± 5.7 days) was significantly longer than those for MCA and ACA aneurysms.
Table 2.
Characteristics of Aneurysm Size, Maximal Size of Keyhole, Operation Time, Postoperative Hospitalization, and State of Clipping in MCA, ACA, and ICA Aneurysms
| Variable | All (n = 350) | (1) MCA (n = 196) | (2) ACA (n = 81) | (3) ICA (n = 73) |
P-Value (3-groups test) Pairwise Comparison |
|---|---|---|---|---|---|
| Aneurysm size (mm) | 6.1 ± 1.9 | 6.4 ± 1.9 | 6.2 ± 1.8 | 5.5 ± 1.8 |
P < 0.01 (1) vs (3): **, (2) vs (3): * |
| Size of keyhole (mm) | 26.5 ± 3.4 | 25.3 ± 2.8 | 28.8 ± 3.5 | 27.1 ± 3.1 |
P < 0.001 (1) vs (2): **, (1) vs (3): **, (2) vs (3): * |
| Operation time (min) | 181 ± 39 | 176 ± 39 | 199 ± 39 | 174 ± 33 |
P < 0.001 (1) vs (2): **, (2) vs (3): * |
| Hospitalization (days) | 2.7 ± 3.6 | 2.5 ± 3.1 | 2.6 ± 2.0 | 3.2 ± 5.7 |
P < 0.01 (1) vs (2): *, (1) vs (3): ** |
| State of clipping | |||||
| Complete neck clipping | 339 (96.9%) | 192 (98.5%) | 79 (97.5%) | 67 (91.8%) | NS |
| Neck remnant | 8 (2.2%) | 2 (1.0%) | 2 (2.5%) | 4 (5.5%) | NS |
| Dome remnant | 3 (0.9%) | 1 (0.5%) | 0 (0%) | 2 (2.7%) | NS |
Mean values are presented as the mean ± SD. 3-groups test: by Kruskal-Wallis test. Pairwise comparison: by Mann-Whitney U test (**: P < 0.01, *: P < 0.05).
ACA, anterior cerebral artery; ICA , internal carotid artery; MCA , middle cerebral artery; NS, not significant
The complete clipping rate was 96.9%, and neck remnant and dome remnant (wrapping) occurred in 8 (2.2%) and 3 (0.9%) cases, respectively, among all 350 UIAs. MCA, ACA, and ICA aneurysms showed no significant differences, but the complete clipping (91.8%) rate for ICA aneurysms was the lowest among the 3 groups.
Surgical complications
Table 3 shows the perioperative complications and postoperative MRI findings. Two patients experienced symptomatic complete stroke due to lacunar infarction, one had hemiparesis (mRS 3), which persisted, and the other had word fluency trouble (mRS 2), which resolved at 1 year. Two patients had an MMSE score of less than 24. The rate of perioperative complications was 4.0% among all 350 patients, but surgical morbidity, defined by the ISUIA study (mRS >2 or MMSE <24) was 0.9%. MCA, ACA, and ICA aneurysms showed no significant differences in perioperative complications, morbidity, or chronic subdural hematoma. Eleven patients (3.1%) showed lacunar infarction on postoperative diffusion-weighted imaging and 7 of these 11 patients were asymptomatic. Lacunar infarction was most common with MCA aneurysm (9 cases, 4.6%). Eight of these 9 lacunar infarctions occurred with the pterional keyhole (5.0%) and one occurred with the sphenoid ridge keyhole approach (2.8%). No cortical infarction or hemorrhagic complication was noted.
Table 3.
Complications after Keyhole Clipping Surgeries in All, MCA, ACA, and ICA Aneurysms
| Variable | All (n = 350) | (1) MCA (n = 196) | (2) ACA (n = 81) | (3) ICA (n = 73) |
P-Value (3-groups test) |
|---|---|---|---|---|---|
| Perioperative complication | |||||
| Complete stroke | 2 | 1 (mRS 2) | 0 | 1 (mRS 3) | NS |
| RIND | 2 | 2 | 0 | 0 | NS |
| Oculomotor palsy | 1 | 0 | 0 | 1 | NS |
| Anosmia | 1 | 0 | 1 | 0 | NS |
| Facial palsy | 1 | 1 | 0 | 0 | NS |
| Epilepsy | 3 | 2 | 1 | 0 | NS |
| MMSE <24 | 2 | 2 | 0 | 0 | NS |
| Infection | 2 | 1 | 1 | 0 | NS |
| Total (%) | 14 (4.0%) | 9 (2.6%) | 3 (3.7%) | 2 (2.7%) | NS |
| Morbidity (mRS >2 or MMSE <24) | 3 (0.9%) | 2 (1.0%) | 0 (0%) | 1 (1.4%) | NS |
| CSDH | 12 (3.4%) | 5 (2.6%) | 2 (2.5%) | 5 (6.8%) | NS |
| MRI findings | |||||
| Lacunar infarction | 11 (3.1%) | 9 (4.6%) | 1 (1.2%) | 1 (1.4%) | NS |
| Cortical infarction | 0 | 0 | 0 | 0 | |
| Venous infarction | 1 | 1 | 0 | 0 | NS |
| Contusion | 0 | 0 | 0 | 0 | |
| Other intracranial hemorrhage | 0 | 0 | 0 | 0 | |
3-groups test: by chi-square test.
ACA, anterior cerebral artery; CSDH, chronic subdural hematoma; ICA, internal carotid artery; MCA, middle cerebral artery; MMSE, Mini-Mental State Examination; mRS, modified Rankin Scale; NS, not significant; RIND, reversible ischemic neurological deficits
Long-term clinical and cognitive status and anxiety/depressive state
The mean clinical follow-up period was 6.6 ± 4.4 years (range 1-19 years). During the follow-up period, 7 patients (2.0%) were lost to follow-up at 1 year after keyhole clipping and 13 patients (3.7%) died of unrelated causes such as cancer and myocardial infarction, except for 1 patient who died of SAH due to rupture of an untreated ICA fusiform aneurysm. Three patients (0.9%) suffered SAH, 2 from rupture of untreated aneurysms (a contralateral MCA aneurysm and an ICA fusiform aneurysm) and 1from rupture of a recurrent PcomA aneurysm 18 years after keyhole clipping at the age of 90 years. The clinical follow-up data at each time point are shown in Table 4. Overall, mRS after keyhole clipping showed no significant change throughout the observation period. Although 2 patients had an MMSE score of less than 24 at 3 months, 4 patients at 1 year, and 5 patients at the last examination after keyhole clipping, MMSE scores did not change significantly throughout the follow-up period. Morbidity (mRS >2 or MMSE <24) at 3 months, 1 year, and the last examination was 2 in 350 patients (0.9%), 5 in 343 patients (1.5%), and 6 in 339 patients (1.8%), respectively. Neither neurological status nor cognitive function changed significantly throughout the follow-up period among all patients, including those with MCA, ACA, and ICA aneurysms.
Table 4.
Comparisons of Neurological Status before and after Keyhole Clipping in All, MCA, ACA, and ICA Aneurysms
| Variable | (1) Preop | (2) At 3 mo | (3) At 1 y | (4) Last |
P-Value (4-points test) Pairwise Comparison |
|---|---|---|---|---|---|
| All (n = 350) | At 6.6 ± 4.4 y | ||||
| mRS score | 0.01 ± 0.08 | 0.02 ± 0.21 | 0.02 ± 0.20 | 0.02 ± 0.20 | NS |
| MMSE score | 28.9 ± 1.7 | 29.2 ± 1.5 | 29.1 ± 1.6 | 28.9 ± 2.0 | NS |
| BDI score | 6.5 ± 5.6 | 2.1 ± 3.1 | <0.001 | ||
| HAM-D score | 4.2 ± 3.8 | 1.5 ± 2.0 | <0.001 | ||
| MCA (n = 196) | At 6.5 ± 4.5 y | ||||
| mRS score | 0.00 ± 0.00 | 0.02 ± 0.17 | 0.02 ± 0.12 | 0.01 ± 0.10 | NS |
| MMSE score | 29.0 ± 1.7 | 29.3 ± 1.6 | 29.2 ± 1.6 | 29.0 ± 1.9 | NS |
| BDI score | 6.2 ± 5.2 | 2.4 ± 3.0 | <0.001 | ||
| HAM-D score | 4.1 ± 4.0 | 1.5 ± 1.8 | <0.001 | ||
| ACA (n = 81) | At 6.8 ± 4.2 y | ||||
| mRS score | 0.00 ± 0.00 | 0.01 ± 0.11 | 0.03 ± 0.16 | 0.01 ± 0.11 | NS |
| MMSE score | 28.9 ± 1.7 | 29.1 ± 1.4 | 29.0 ± 1.7 | 28.6 ± 2.1 | NS |
| BDI score | 7.8 ± 6.5 | 1.8 ± 2.4 | <0.001 | ||
| HAM-D score | 4.7 ± 3.7 | 1.7 ± 2.1 | <0.001 | ||
| ICA (n = 73) | At 6.6 ± 4.5 y | ||||
| mRS score | 0.03 ± 0.16 | 0.04 ± 0.35 | 0.04 ± 0.36 | 0.06 ± 0.38 | NS |
| MMSE score | 28.9 ± 1.9 | 29.3 ± 1.3 | 29.1 ± 1.3 | 28.9 ± 2.0 | NS |
| BDI score | 5.6 ± 5.5 | 2.0 ± 3.9 | <0.001 | ||
| HAM-D score | 3.9 ± 3.6 | 1.4 ± 2.4 | <0.001 |
Mean values are presented as the mean ± SD. 4-points test: by Friedman test; . Pairwise (2-points) comparison: by Wilcoxon signed-rank test (P < 0.01, P < 0.05).
ACA, anterior cerebral artery; BDI, Beck Depression Inventory; HAM-D, Hamilton Rating Scale for Depression; ICA, internal carotid artery; MCA, middle cerebral artery; MMSE, Mini-Mental State Examination; mRS, modified Rankin Scale; NS, not significant
Anxiety and depression, as assessed by both BDI and HAM-D were significantly improved at 3 months after the operation. Such improvements were also observed in patients with MCA, ACA, and ICA aneurysms.
Long-term radiological follow-up
The mean radiological follow-up period was 7.1 ± 4.6 years (range 1-19 years). Table 5 shows the numbers of regrowth of aneurysm remnant, aneurysm recurrence, de novo aneurysm, and retreatment in each location. One patient with an MCA aneurysm had regrowth among 3 with aneurysm remnants and underwent re-clipping 1 year after keyhole clipping. Neither of the 2 patients with neck remnants in ACA aneurysms showed regrowth, although 1 showed aneurysm recurrence but was not re-treated. One of the 6 patients with remnant ICA aneurysm showed regrowth and underwent re-clipping 8 years after keyhole clipping. Two patients showed aneurysm recurrence, and 1 suffered rupture 18 years later at the age of 90 years after keyhole clipping and was re-treated by coiling. In total, 2 of 11 aneurysm remnants showed regrowth (18.1%, 1.6%/year), 3 showed aneurysm recurrence (0.9%, 0.1%/year), and 3 patients required retreatment (0.9%, 0.1%/year). The incidence of rupture after keyhole clipping was 0.3% (0.04%/year). De novo aneurysms were found during follow-up in 21 cases, but all were small and none required treatment. These radiological findings were not significantly different between MCA, ACA, and ICA aneurysms.
Table 5.
Regrowth of Aneurysm Remnant, Recurrence, and De Novo Aneurysm in All, MCA, ACA, and ICA Aneurysms
| Variable | All (n = 350) | MCA (n = 196) | ACA (n = 81) | ICA (n = 73) | P-Value (3-groups test) |
|---|---|---|---|---|---|
| Regrowth of remnant (%/year) | 2 (1.6) | 1 (1.9) | 0 (0) | 1 (2.3) | NS |
| Aneurysm recurrence (%/year) | 3 (0.1) | 0 (0) | 1 (0.17) | 2 (0.6) | NS |
| De novo aneurysm (%/year) | 21 (0.9) | 13 (1.0) | 3 (0.5) | 5 (1.4) | NS |
| Retreatment (%/year) | 3 (0.1) | 1 (0.1) | 0 (0) | 2 (0.4) | NS |
3-groups test: by chi-square test.
ACA, anterior cerebral artery; ICA, internal carotid artery; MCA , middle cerebral artery; NS, not significant
Discussion
Good UIA candidates for keyhole clipping
The generally accepted ideal candidates for surgical clipping include anterior circulation aneurysms, especially those located superficially such as MCA aneurysms, and small aneurysms less than 10 mm in size.13) The PHASES (Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid hemorrhage from another aneurysm, Site of aneurysm) score based on pooled analysis of prospective cohort studies can be used for clinical decision-making in patients with UIAs, and identifies the PcomA, AcomA, ACA, and MCA as sites of aneurysms that tend to rupture.14) Our study showed that the aneurysms treated by keyhole clipping were all anterior circulation UIAs; MCA aneurysms were most frequently treated, followed by AcomA and PcomA aneurysms, and were generally less than 10 mm in size. These locations and sizes of UIAs favored for keyhole clipping are generally accepted.15) UIAs that are generally difficult to clip even with conventional craniotomy, are not candidates for keyhole clipping. Therefore, keyhole clipping is not suitable for the following types of MCA, AcomA, and ICA aneurysms: short M1, M1, or posterior-projecting MCA aneurysms, posterior-projecting or high-positioned AcomA aneurysms, and retrocarotid, low-lying, or highly perforator-involved ICA aneurysms. Successful and safe keyhole clipping of UIAs depends mainly on selecting aneurysms suitable for the keyhole approach in each location based on the specific characteristics as described in Table 1.
The keyhole approach has drawbacks such as limited working space and a narrowed working angle compared with the conventional craniotomy approach, which hinders the safe manipulation and clipping of large and/or complicated UIAs.
Demographic data and surgical occlusion rate of UIAs by keyhole clipping
In the present study, the mean aneurysm size was significantly smaller and the mean hospitalization time for ICA aneurysms was significantly longer than those for MCA and ACA aneurysms. An MRA-based brain dock examination of Japanese adults showed that 93% of ICA aneurysms (C1 and C2) were small (less than 5 mm diameter).16) We previously reported that keyhole clipping of ICA aneurysms carries a higher risk of dog-ear neck remnant, and recommended stricter indication criteria, limiting it to small aneurysms.17) Consequently, the mean size of ICA aneurysms was significantly smaller than that of MCA and ACA aneurysms. One of our patients with an ICA aneurysm suffered hemiparesis and required 51 days of rehabilitation, resulting in significantly longer mean hospitalization time for ICA aneurysms compared to MCA and ACA aneurysms.
In the present study, the mean craniotomy size was significantly larger and the mean operation time was significantly longer for ACA aneurysms than for MCA and ICA aneurysms. This reason is because AcomA aneurysms require wider operative fields and more time to access and dissect the aneurysms.
Occlusion rates of small UIAs are generally high with both surgical clipping and endovascular treatment. A multicenter surgical series of 228 very small UIAs (mostly in the anterior circulation) showed a complete occlusion rate of 98.2%.18) A meta-analysis of endovascular studies with 261 small UIAs showed a complete occlusion rate of 85% with a 6% retreatment rate.19) The complete occlusion rate in the present study was 96.9% by keyhole clipping. Therefore, careful selection of candidates for keyhole clipping can result in neck clipping rates via keyhole craniotomy that are comparable to those of conventional craniotomy. However, the complete clipping rate of ICA aneurysms was the lowest (91.8%), although the difference was not statistically significant. The clip used to obliterate an ICA aneurysm can prevent microscopic observation of the clipping status, especially in low-lying ICAs. Therefore, endoscopic observation should be used to check for any neck remnant of the ICA aneurysm behind the clip blade.
Safety of keyhole clipping of UIAs
Endovascular treatment remains superior to clipping in terms of disability and complications, despite the higher rate of unruptured aneurysm recurrence.20) A subanalysis of the ISUIA cohort showed overall morbidity and mortality including cognitive impairment of 12.6% for clipping and 9.8% for endovascular coiling at 1 year.12) A recent meta-analysis reported that surgical mortality and morbidity (mRS >2) for UIAs in the anterior circulation were 0.15% and 3.0%, respectively.21) A multicenter surgical series with 228 very small UIAs (mostly anterior circulation) reported no mortality after clipping and permanent neurological morbidity of 2.7%.18) A meta-analysis of endovascular treatments of small UIAs showed mortality and morbidity in 4%.19) In the present study, mortality was 0% and morbidity (mRS >2 or MMSE <24) was 0.9%. Keyhole clipping is considered to be unsafe due to its narrow surgical field and smaller working angle, which obstruct both observation and manipulation of the aneurysm from various directions. However, strict selection of UIAs suitable for keyhole clipping, careful preoperative simulation using 3D imaging, and the surgeon's experience can ensure safe keyhole clipping. In the present study, the rate of lacunar infarction was highest with MCA aneurysms (4.6%), particularly MCA aneurysms treated using the pterional keyhole approach (5.0%) although this was not statistically significant. The surgical trajectory via the pterional keyhole follow a straight axis, making it difficult to observe the lateral lenticulostriate artery located behind the aneurysm. Therefore, we have shifted to using the sphenoid ridge keyhole approach for MCA aneurysms, which provides a wider surgical angle to observe the perforators behind the aneurysm and has a lower lacunar infarction rate (2.8%).
Hospital stay after treatment
Longer hospitalization is one of the disadvantages of open surgical clipping. A retrospective cohort study of 2535 patients with UIA based on information from 18 American states found that the endovascular coiling cohort had an average hospital stay of 4.5 days, compared with 7.4 days in the surgical clipping cohort.22) Advanced coiling techniques have further shortened the average length of stay to 2.2 days.23) The present study found that the average hospitalization after keyhole clipping was 2.7 ± 3.6 days, with 88% of patients discharged within 3 days. Our average hospitalization after keyhole clipping for UIA is comparable to that of endovascular treatment. A shorter hospital stay can be achieved through less invasive operations with a lower complication rate. Minimizing hospital stay ensures high-quality medical care, lower medical costs, and early reintegration into society after treatment.23,24) Indeed, short hospital stay and early psychological improvement after keyhole clipping both contribute to a better quality of life after treatment.6)
Preserved cognitive function and improved psychological state after keyhole clipping
The ISUIA study showed that neuropsychological impairment as well as functional disability are major determinants of morbidity after treatment of UIAs, so examination of cognitive function is mandatory to assess the postoperative state. According to the ISUIA, the rates of impaired cognitive function (MMSE <24) were 8.5% for surgical clipping and 5.4% for endovascular coiling. In the present study, only 2 patients (0.6%) showed MMSE <24 and morbidity (mRS >2 or MMSE <24) was 0.9%. The mRS and MMSE did not change significantly throughout the follow-up period (1-19 years, 6.6 ± 4.4 years). These facts validate the conclusion that keyhole clipping is less invasive, and that both cognitive function and functional state can be preserved for a long time.
Surgical outcomes cannot be evaluated only by measures such as mRS or cognitive function. Subjective and patient-based outcome evaluation is imperative to assess the true surgical outcome after treatment of UIA.25) The ideal outcomes of UIA treatment are to increase life expectancy whilst preventing future aneurysm rupture, which will lead to high life satisfaction for the patient. Life satisfaction and mental state can be diminished by fears about possible future aneurysm rupture, treatment risk, anxiety about poor functional result after treatment, and fear of recurrence. A real-world evaluation reported that 35% of patients with UIA treated by surgical clipping suffered from depression.26) Patients who underwent clipping for UIA continued to have high levels of anxiety and depression, especially during the recovery period (median: 3 months), so the anxiety and depression scores only improved 1 to 3 years after either clipping or coiling.25,27-30) Although endovascular treatment is the first-line strategy for UIA because of superior mortality and morbidity compared to clipping, the prevalences of anxiety and depression in UIA patients treated by endovascular treatment were 17.0% and 15.5%, respectively, at 31 ± 9 months after discharge.31) This persistent depressive state is considered to result from fears of bleeding and recurrence after endovascular intervention. Our present study found that depression and anxiety scores were significantly improved soon after clipping treatment (at 3 months). We assume this prompt improvement in depressive mood was aligned with the quick recovery without sequelae after the less invasive keyhole operation. We explained to the patients that completely clipped UIAs rarely bleed or recur, which relieved anxiety and helped to improve depression scores at 3 months after keyhole clipping.
Very low aneurysm recurrence and retreatment rate after keyhole clipping
The incidence of aneurysm remnants after conventional surgical clipping is 4.6%-18%.32-34) The incidence of regrowth of the aneurysm remnant is 1.8%-2.1% per year, and the total regrowth rate is 12.5%-27%.35) Although aneurysm recurrence after complete clipping is considered to be low, the incidence of recurrent aneurysm after complete clipping is 0.14%-2.4% and the annual incidence is 0.02%-0.26%.32,36,37) A recent study using 3D CTA showed regrowth of an aneurysm remnant occurred in 11.8% of cases (3.4%/year) and aneurysm recurrence after conventional clipping was 2.7% (0.7%/year).38) The retreatment rate for conventional surgical clipping of UIA is 0.4%-4.6%.18,39) The incidence of rupture of recurrent aneurysm is 0%-0.3%.32,36) In the present study, with a mean follow-up period of 7.1 ± 4.6 years (1-19 years), the incidence of aneurysm remnant after keyhole clipping was 3.1%, regrowth of the remnant was 18.1% (1.6%/year), recurrence was 0.9% (0.1%/year), retreatment was 0.9% (0.1%/year), and rupture was 0.3% (0.04%/year). The durability of keyhole clipping is comparable to or better than that of clipping via conventional craniotomy. Aneurysm remnant and recurrence are common with AcomA and ICA anurysms, especially PcomA, aneurysms.33,40) In the present study, ICA aneurysms had the highest incidence of aneurysm neck remnant (5.5%) and recurrence (0.6%/year), although the difference were not significant. The present study showed low incidences of neck remnant and recurrence in AcomA aneurysms compared to PcomA aneurysm, because mostly anteriorly or inferiorly projecting aneurysms were treated. Aneurysm remnant and recurrence tend to occur with larger aneurysms (>12 mm).33) Our series treated relatively small (<10 mm) anterior circulation aneurysms and consequently showed very low recurrence and retreatment rates. Over many years, aneurysm recurrence and retreatment rates of <1% affirm that keyhole clipping for relatively small anterior circulation aneurysms can be substantially considered curative and that no follow-up imaging may be needed.38) The risk of aneurysm recurrence after endovascular treatment is higher than with surgical clipping, so all patients are advised to return periodically after endovascular treatment for angiography to monitor for residual or recurring aneurysm. This increases anxiety for a long time after endovascular intervention. Although endovascular treatment is generally considered the standard for UIA, physicians should consider these findings when making treatment recommendations for individual patients.
Conclusions
Our present study confirmed that keyhole clipping of relatively small anterior circulation UIA results in low morbidity including preserved cognitive function, short hospitalization, early recovery from depression and anxiety, and very low aneurysm recurrence and retreatment rates, which indicates that keyhole clipping is curative. Only such a less invasive and potentially curative treatment modality can ensure better quality of life with psychological comfort.
Disclaimer
Author Kojiro Wada is one of the Editorial Board members of the Journal. This author was not involved in the peer-review or decision-making process for this paper.
Conflicts of Interest Disclosure
All authors have no conflict of interest.
Supplementary Material
Four types of keyhole craniotomy to clip an unruptured intracranial aneurysm. A: Pterional keyhole to clip the MCA aneurysm. B: Sphenoid ridge keyhole to clip the MCA aneurysm. C: Supraorbital keyhole to clip ICA and AcomA aneurysms. D: Unilateral interhemispheric keyhole to clip distal ACA aneurysm.
ACA: anterior cerebral artery; AcomA: anterior communicating artery; ICA: internal cerebral artery; MCA: middle cerebral artery.
Locations of unruptured intracranial aneurysms treated by keyhole clipping (A) and types of keyhole approach (B). A1: A1 portion of the ACA; ACA genu: genu of the anterior cerebral artery; AcomA: anterior communicating artery; AchoA: anterior choroidal artery; ICA: internal carotid artery; ICA para: internal carotid artery paraclinoid; ICA top: top of the internal cerebral artery; MCA: middle cerebral artery; PcomA: posterior communicating artery.
References
- 1).Brinjikji W, Rabinstein AA, Nasr DM, et al. Better outcomes with treatment by coiling relative to clipping of unruptured intracranial aneurysms in the United States, 2001-2008. AJNR Am J Neuroradiol. 2011;32(6):1071-5. doi: 10.3174/ajnr.A2453 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2).Hulsbergen AFC, Mirzaei L, van der Boog ATJ, et al. Long-term durability of open surgical versus endovascular repair of intracranial aneurysm: a systematic review and meta-analysis. World Neurosurg. 2019;132:e820-33. doi: 10.1016/j.wneu.2019.08.002 [DOI] [PubMed] [Google Scholar]
- 3).Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. 2002;360(9342):1267-74. doi: 10.1016/s0140-6736(02)11314-6 [DOI] [PubMed] [Google Scholar]
- 4).Mori K, Wada K, Otani N, et al. Validation of effectiveness of keyhole clipping in nonfrail elderly patients with unruptured intracranial aneurysms. J Neurosurg. 2017;127(6):1307-14. doi: 10.3171/2016.9JNS161634 [DOI] [PubMed] [Google Scholar]
- 5).Mori K, Wada K, Otani N, et al. Long-term neurological and radiological results of consecutive 63 unruptured anterior communication artery aneurysms clipped via lateral supraorbital keyhole minicraniotomy. Oper Neurosurg. 2018;14(2):95-103. doi: 10.1093/ons/opx244 [DOI] [PubMed] [Google Scholar]
- 6).Mori K, Wada K, Otani N, et al. Keyhole strategy aiming at minimizing hospital stay for surgical clipping of unruptured middle cerebral artery aneurysms. J Neurosurg. 2019;130(4):1359-66. doi: 10.3171/2017.10.JNS171973 [DOI] [PubMed] [Google Scholar]
- 7).Figueiredo EG, Welling LC, Preul MC, et al. Surgical experience of minipterional craniotomy with 102 ruptured and unruptured anterior circulation aneurysms. J Clin Neurosci. 2016;27:34-9. doi: 10.1016/j.jocn.2015.07.032 [DOI] [PubMed] [Google Scholar]
- 8).Reisch R, Perneczky A. Ten-year experience with the supraorbital subfrontal approach through an eyebrow skin incision. Neurosurgery. 2005;57(suppl):242-55. doi: 10.1227/01.neu.0000178353.42777.2c [DOI] [PubMed] [Google Scholar]
- 9).Perneczky A, Fries G. Endoscope-assisted brain surgery: part 1--evolution, basic concept, and current technique. Neurosurgery. 1998;42(2):219-25. doi: 10.1097/00006123-199802000-00001 [DOI] [PubMed] [Google Scholar]
- 10).Nathal E, Gomez-Amador JL. Anatomic and surgical basis of the sphenoid ridge keyhole approach for cerebral aneurysms. Neurosurgery. 2005;56(suppl):178-85. doi: 10.1227/01.neu.0000145967.66852.96 [DOI] [PubMed] [Google Scholar]
- 11).Fukushima T, Miyazaki S, Takusagawa Y, et al. Unilateral interhemispheric keyhole approach for anterior cerebral artery aneurysms. Acta Neurochir Suppl (Wien). 1991;53:42-7. doi: 10.1007/978-3-7091-9183-5_8 [DOI] [PubMed] [Google Scholar]
- 12).Wiebers DO, Whisnant JP, Huston J 3rd, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103-10. doi: 10.1016/s0140-6736(03)13860-3 [DOI] [PubMed] [Google Scholar]
- 13).Ajiboye N, Chalouhi N, Starke RM, et al. Unruptured cerebral aneurysms: evaluation and management. ScientficWorldJournal. 2015;2015:954954. doi: 10.1155/2015/954954 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14).Greving JP, Wermer MJH, Brown RD Jr, et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol. 2014;13(1):59-66. doi: 10.1016/S1474-4422(13)70263-1 [DOI] [PubMed] [Google Scholar]
- 15).Rathore L, Yamada Y, Kawase T, et al. The keyhole approach in anterior circulation aneurysm--Current indication and limitation with review of literature. Asian J Neurosurg. 2020;15(2):278-84. doi: 10.4103/ajns.AJNS_25_19 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16).Imaizumi Y, Mizutani T, Shimizu K, et al. Detection rates and sites of unruptured intracranial aneurysms according to sex and age: an analysis of MR angiography-based brain examinations of 4070 healthy Japanese adults. J Neurosurg. 2018;130(2):573-8. doi: 10.3171/2017.9.JNS171191 [DOI] [PubMed] [Google Scholar]
- 17).Toyooka T, Wada K, Otani N, et al. Potential risks and limited indications of the supraorbital keyhole approach for clipping internal carotid artery aneurysms. World Neurosurg X. 1019;2:100025. doi: 10.1016/j.wnsx.2019.100025 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18).Bruneau M, Amin-Hanjani S, Koroknay-Pal P, et al. Surgical clipping of very small unruptured intracranial aneurysms: a multicenter international study. Neurosurgery. 2016;78(1):47-52. doi: 10.1227/NEU.0000000000000991 [DOI] [PubMed] [Google Scholar]
- 19).Yamaki VN, Brinjikji W, Murad MH, et al. Endovascular treatment of very small intracranial aneurysms: meta-analysis. AJNR Am J Neuroradiol. 2016;37(5):862-7. doi: 10.3174/ajnr.A4651 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20).Hwang JS, Hyun MK, Lee HJ, et al. Endovascular coiling versus neurosurgical clipping in patients with unruptured intracranial aneurysm: a systematic review. BMC Neurol. 2012;12:99. doi: 10.1186/1471-2377-12-99 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21).Fotakopoulos G, Lempesis IG, Georgakopoulou VE, et al. Surgical outcomes of patients with unruptured anterior vs. inferior circulation aneurysms: a meta-analysis. Med Int (Lond). 2023;4:5. doi: 10.3892/mi.2023.129 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22).Higashida RT, Lahue BJ, Torbey MT, et al. Treatment of unruptured intracranial aneurysms: a nationwide assessment of effectiveness. AJNR Am J Neuroradiol. 2007;28(1):146-51. [PMC free article] [PubMed] [Google Scholar]
- 23).Duan Y, Blackham K, Nelson J, et al. Analysis of short-term total hospital costs and current primary cost drivers of coiling versus clipping for unruptured intracranial aneurysms. J Neurointerv Surg. 2015;7(8):614-8. doi: 10.1136/neurintsurg-2014-011249 [DOI] [PubMed] [Google Scholar]
- 24).Hoshikuma Y, Shimizu T, Toyota S, et al. Statistical analysis of the factors that affect postoperative length of hospital stay after unruptured intracranial aneurysm treatment in Japan: a 20-year nationwide multicenter study. Neurol Med Chir (Tokyo). 2024;64(4):154-9. doi: 10.2176/jns-nme.2023-0142 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25).Yamashiro S, Nishi T, Koga K, et al. Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms. J Neurol Neurosurg Psychiatry. 2007;78(5):497-500. doi: 10.1136/jnnp.2006.098871 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26).Lim YC, Lee E, Song J. Depression or anxiety according to management modalities in patients with unruptured intracranial aneurysms. Stroke. 2022;53(12):3662-70. doi: 10.1161/STROKEAHA.122.040330 [DOI] [PubMed] [Google Scholar]
- 27).Backes D, Rinkel GJE, van der Schaaf IC, et al. Recovery to preinterventional functioning, return-to-work, and life satisfaction after treatment of unruptured aneurysm. Stroke. 2015;46(6):1607-12. doi: 10.1161/STROKEAHA.115.008795 [DOI] [PubMed] [Google Scholar]
- 28).Brilstra EH, Rinkel GJE, van der Graaf Y, et al. Quality of life after treatment of unruptured intracranial aneurysms by neurosurgical clipping or by embolization with coils. A prospective, observational study. Cerebrovasc Dis. 2004;17(1):44-52. doi: 10.1159/000073897 [DOI] [PubMed] [Google Scholar]
- 29).Otawara Y, Ogasawara K, Kubo Y, et al. Anxiety before and after surgical repair in patients with asymptomatic unruptured intracranial aneurysm. Surg Neurol. 2004;62(1):28-31. doi: 10.1016/j.surneu.2003.07.012 [DOI] [PubMed] [Google Scholar]
- 30).Solheim O, Eloqayli H, Muller TB, et al. Quality of life after treatment for incidental, unruptured intracranial aneurysms. Acta Neurochir (Wien). 2006;148(8):821-30. doi: 10.1007/s00701-006-0804-7 [DOI] [PubMed] [Google Scholar]
- 31).Zhai XD, Yu JX, Ma YJ, et al. Prevalence of and risk factors for anxiety and depression in Chinese patients with unruptured intracranial aneurysms treated by endovascular intervention. BMC Psychiatry. 2020;20(1):430. doi: 10.1186/s12888-020-02834-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32).Burkhardt JK, Chua MHJ, Weiss M, et al. Risk of aneurysm residual regrowth, recurrence, and de novo aneurysm formation after microsurgical clip occlusion based on follow-up with catheter angiography. World Neurosurg. 2017;106:74-84. doi: 10.1016/j.wneu.2017.06.110 [DOI] [PubMed] [Google Scholar]
- 33).Jabbarli R, Pierscianek D, Wrede K, et al. Aneurysm remnant after clipping: the risks and consequences. J Neurosurg. 2016;125859:1249-55. doi: 10.3171/2015.10.JNS151536 [DOI] [PubMed] [Google Scholar]
- 34).Thornton J, Bashir Q, Aletich VA, et al. What percentage of surgically clipped intracranial aneurysms have residual necks? Neurosurgery. 2000;46(6):1294-8. doi: 10.1097/00006123-200006000-00003 [DOI] [PubMed] [Google Scholar]
- 35).Piao J, Luan T, Qu L, et al. Intracranial post-clipping residual or recurrent aneurysms: current status and treatment options. Med Int (Lond). 2021;1(1):1. doi: 10.3892/mi.2021.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36).Brown MA, Parish J, Guandique CF, et al. A long-term study of durability and risk factors for aneurysm recurrence after microsurgical clip ligation. J Neurosurg. 2017;126(3):819-24. doi: 10.3171/2016.2.JNS152059 [DOI] [PubMed] [Google Scholar]
- 37).Tsutsumi K, Ueki K, Morita A, et al. T. Risk of aneurysm recurrence in patients with clipped cerebral aneurysms: results of long-term follow-up angiography. Stroke. 2001;32(5):1191-4. doi: 10.1161/01.str.32.5.1191 [DOI] [PubMed] [Google Scholar]
- 38).Marbacher S, Grüter BE, Wanderer S, et al. Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography. J Neurosurg. 2023;138(3):717-23. doi: 10.3171/2022.5.JNS22424 [DOI] [PubMed] [Google Scholar]
- 39).Daileda T, Vahidy FS, Chen PR, et al. Long-term retreatment rates of cerebral aneurysms in a population-level cohort. J NeuroInterv Surg. 2019;11(4):367-72. doi: 10.1136/neurointsurg-2018-014112 [DOI] [PubMed] [Google Scholar]
- 40).Okada T, Ishikawa T, Moroi J, et al. Timing of retreatment for patients with previously coiled or clipped intracranial aneurysms: analysis of 156 patients with multiple treatments. Surg Neurol Int. 2016;7(suppl 2):S40-8. doi: 10.4103/2152-7806.173570 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Four types of keyhole craniotomy to clip an unruptured intracranial aneurysm. A: Pterional keyhole to clip the MCA aneurysm. B: Sphenoid ridge keyhole to clip the MCA aneurysm. C: Supraorbital keyhole to clip ICA and AcomA aneurysms. D: Unilateral interhemispheric keyhole to clip distal ACA aneurysm.
ACA: anterior cerebral artery; AcomA: anterior communicating artery; ICA: internal cerebral artery; MCA: middle cerebral artery.
Locations of unruptured intracranial aneurysms treated by keyhole clipping (A) and types of keyhole approach (B). A1: A1 portion of the ACA; ACA genu: genu of the anterior cerebral artery; AcomA: anterior communicating artery; AchoA: anterior choroidal artery; ICA: internal carotid artery; ICA para: internal carotid artery paraclinoid; ICA top: top of the internal cerebral artery; MCA: middle cerebral artery; PcomA: posterior communicating artery.