Clinical Neurology and Neurosurgery 122 (2014) 42–49
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Surgical outcome of primary clipping for anterior circulation aneurysms of size 2 centimeters or larger Sunil V. Furtado *, Narayanam A. Saikiran, Sumit Thakar, Ravi Dadlani, Dilip Mohan, Saritha Aryan, Alangar S. Hegde Department of Neurosurgery, Sri Sathya Sai Institute Of Higher Medical Sciences, EPIP Area, Whitefield, Bangalore 560066, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 December 2013 Received in revised form 3 March 2014 Accepted 13 April 2014 Available online 22 April 2014
Background: Aneurysms of the anterior circulation larger than 2 cm have a complex relationship to the anterior skull base, requiring a multi-modality management approach. This retrospective study of 54 patients with such aneurysms who underwent clipping between 2001 and 2012 analyzes clinical and surgical data, aneurysm characteristics and correlates them with respect to the Glasgow outcome score at follow-up and immediate post-operative clinical status. Methods: Patients with an outcome score of 5 or 4 were categorized as “good", while those with score 3–1 were “poor”. Fisher’s exact test and paired T-test (p < 0.5) were used to test statistical significance for discrete and continuous variables respectively. Results: 44 (81.4%) patients had a good outcome. Patients with non-ophthalmic/paraclinoid aneurysms had significantly lower incidence of adverse intra-operative events (p = 0.035). Patients older than 50 years (p = 0.045), with adverse intra-operative events (p = 0.015) and post-operative infarction (p < 0.001) had a poor outcome compared to those younger than 50 years age and those without adverse intraoperative events or infarctions. The grouped age variable had maximum influence on patient outcome. Location and size of aneurysm did not have an overall impact on surgical outcome. There were 4 mortalities. Conclusions: Primary clipping of proximal non-cavernous aneurysms on the internal carotid artery is associated with adverse intra-operative events. A multi-modality treatment approach in these aneurysms should be individualized, more so in patients older than 50 years. ã 2014 Elsevier B.V. All rights reserved.
Keywords: Giant aneurysm Anterior circulation Clipping Intracranial hemorrhage SAH
1. Introduction Surgical approach to proximal large and giant anterior circulation aneurysms is challenged by their relationship to the skull base, cavernous sinus and cranial nerves in close proximity. The 5-year cumulative rupture rate for anterior circulation aneurysms of size 13–24 mm and 25 mm or greater is 14.5% and 40% respectively [1,2]. Two-thirds of giant aneurysms are diagnosed before rupture, mainly due to mass effect on cranial nerves, besides presenting with; seizures, repeated TIAs (transient ischemic attacks) or subarachnoid hemorrhage [3]. Flow-related large and giant aneurysms are usually located at the branching regions on the parent vessel [4].
* Corresponding author at: Sri Sathya Sai Institute of Higher Medical Sciences, Department of Neurosurgery, EPIP Area, Whitefield, Bangalore 560066, India. Tel.: +91 80 28416837. E-mail address: [email protected] (S.V. Furtado). http://dx.doi.org/10.1016/j.clineuro.2014.04.012 0303-8467/ ã 2014 Elsevier B.V. All rights reserved.
There have been many advances in the exclusion of large and giant aneurysms from the native circulation since 1885 when Horsley first recorded surgical management (by proximal carotid ligation) of a giant aneurysm located in the pre-cavernous segment of the ICA [3,5,6]. Given the complexity of these aneurysms, there is a high incidence of post-operative morbidity and death associated with surgical exclusion of these aneurysms from the circulation. The risks often exceed the risk of subarachnoid hemorrhage (SAH) from them [1]. This paper addresses the risks associated with primary clipping of aneurysms larger than 2 cm, located in the anterior circulation. The use of microsurgical, endovascular modalities and adjuncts like intra-operative neuromonitoring and blood-flow studies provide a multi-modality approach to treat this complex pathology [7,8]. 2. Materials and methods This retrospective study comprised patients with anterior circulation aneurysms, 2 cm or more in size. These aneurysms are
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categorized as very large and giant aneurysms of the anterior circulation [9]. Over a twelve-year period between January 2001 and June 2012, there were 54 such aneurysms operated and constituted 7.2% of operated aneurysm cases. Of the patients, 26 were male and 28 female, with a mean age of 45.1 years. Other parameters like; patient demographics, symptom at presentation, clinical signs, World federation of neurological societies (WFNS) subarachnoid (SAH) grade at first presentation and functional status at follow-up were mined from the hospital electronic patient database once the subset of aneurysm patients was identified. Radiological images were obtained for review in all cases from the Synapse PACS (Fujifilm Medical Systems, Stamford, CT, USA) system and were used to calculate the size and location of aneurysm and post-surgical aneurysm status. Intra-operative details regarding usage of temporary clip and the duration of temporary clip usage, intra-operative aneurysm rupture, number and configuration of permanent clip used were obtained from the operative notes and video archives. Data were entered in an Excel spreadsheet (Microsoft Inc.,) and analyzed using SPSS version 17 for Windows (SPSS Inc., Chicago, IL). Patients were divided into two groups; good- Glasgow outcome score (GOS) 5 and 4 and poor (3–1) outcome groups, based on their clinical status at the last follow-up visit. Fisher’s exact test two-tailed (p < 0.05) was used to check correlation of clinical outcome with demographic, intra-operative surgical maneuvers and adverse events like aneurysm rupture, clinico-radiological factors pre-and post-surgery. Means and standard deviations were computed for continuous variables. The paired T-test was used to compare differences in ratios between the good and poor outcome groups. 3. Results 3.1. Presentation 28 patients primarily presented with subarachnoid hemorrhage (SAH), 2 with a temporal parenchymal bleed from middle cerebral artery (MCA) aneurysm, 9 presented with headaches with no recorded sub-arachnoid bleed on radiology, 7 had visual abnormalities, 4 had seizures, 3 had oculomotor nerve palsies and 1 had a subdural hematoma. Out of the patients with SAH, 23 had a single ictus. 4 patients bled twice and 1 patient had 3 icti. In addition, 2 patients with SAH also had post-bleed seizures and 2 patients later developed abducens nerve palsy secondary to hydrocephalus. The patients presented between 1 day and 4 years after ictus (median 30 days). Forty-eight patients were in WFNS SAH grade 1 at presentation, 4 in grade 2 and 1 each in grade 3 and 4. On computed tomography (CT) or magnetic resonance (MR) evaluation at the hospital at first presentation and applying the Fisher score for SAH; 32 exhibited Fisher grade 1, 7 were in grade 2,12 had Fisher grade 3 score and 3 had Fisher grade 4 score. Hydrocephalus was seen in 4 patients pre-operatively. A total of 10 patients required an external ventricular drain in the perioperative period (4 pre-operative and 6 post-operative). A total of 6 patients required a ventriculo-peritoneal shunt post-operatively, which included 3 patients from the pre-operative hydrocephalus group. Infarcts were seen pre-operatively in 3 patients involving the parietal MCA territory in 1 patient and distal anterior cerebral artery (DACA) i.e. A4 territory in 2 patients. Calcification in the vessel wall was documented in 5 patients and an intra-aneurysmal thrombus was noted in 21 patients. 21 patients underwent an angiogram to delineate the aneurysm in relation to the skull base. 3.2. Aneurysm characteristics The location of aneurysms is provided in Table 1. Ophthalmic segment aneurysms had a higher incidence (20 cases), followed by
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middle cerebral artery bifurcation (12 cases) and anterior communicating artery aneurysms (11 cases). There was a case of giant A1 segment aneurysm and 2 cases of giant distal anterior cerebral artery aneurysm. Giant aneurysms in the A1 segment and pericallosal region are rare with only a dozen reported cases in each either region [10,11]. These aneurysms are usually associated with arterial anomalies like A1 fenestration, azygos anterior cerebral artery or trauma as in the case of DACA aneurysms, which our patients did not exhibit. The average size of the aneurysms was 2.20 cm (median 2.6; SD 1.10). Two patients with ophthalmic segment aneurysms had small aneurysms in another location (opposite ophthalmic segment and anterior communicating (ACOM) aneurysm). A patient with a posterior communicating segment (PCOM) aneurysm had a Spetzler–Martin grade 1 frontal arterio-venous malformation. Balloon occlusion tests were performed in 49 patients to test the patency of the communicating system and document cross flow. 3.3. Surgery 46 patients with aneurysms underwent a pterional craniotomy and clipping of their anterior circulation aneurysm. 5 patients with ophthalmic segment aneurysms underwent an orbito-zygomatic approach and 2 patients with DACA aneurysms underwent a pericoronal parasagittal craniotomy and 1 patient with a cavernous segment underwent ligation of the cervical internal carotid artery (ICA) under local anesthesia following temporary occlusion of the cervical ICA under hypotensive condition. 52 of the remaining aneurysms were clipped primarily and a giant A1 segment aneurysm was trapped on the A1 segment as the neck was atherosclerotic and the aneurysm could not be clipped with the available clips. Yasargil titanium aneurysm clips (Aesculap Inc., PA) were used in all surgeries. 3 cases (Giant ACOM and 2 ophthalmic segment aneurysms) were operated under total circulatory cardiac arrest under hypothermic conditions. 14 patients with ophthalmic segment aneurysms required drilling of the anterior clinoid process and the roof of optic canal. A temporary clip was used in 32 cases for a mean duration of 5.46 min (median 4 min, range 1–28 min). 37 patients did not have any documented adverse intraoperative events in the operative records which included aneurysm rupture, clip adjustment due to compromise of perforator vessels or communicating vessels of the circle of Willis. Figs. 1–4 show well clipped ACOM, MCA and ophthalmic segment aneurysms in the series. 4. Outcome 4.1. Immediate post-operative 40 (74%) patients were neurologically intact immediately after surgery. 18 (33%) patients had infarcts documented in their postoperative CT or MR images, out of which 10 (18.5%) infarcts involved eloquent areas causing clinical weakness, alteration in sensorium or dysphasia. 3 patients in this group (2 patients with an internal capsular and 1 with a parietal lobar MCA infarct) Table 1 Location of aneurysm. Ophthalmic segment aneurysm Middle cerebral artery aneurysm Anterior communicating artery aneurysm Posterior communicating segment aneurysm Anterior choroidal segment aneurysm Distal anterior cerebral artery aneurysm Anterior cerebral artery aneurysm (A1) Cavernous/clinoid segment ICA aneurysm
20 12 11 5 2 2 1 1
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Fig. 1. DSA anteroposterior (AP) view (A) 2.3 cm ACOM aneurysm (B) with no residual post-clipping.
showed improvement in their motor deficit and had a good GOS at last follow-up. 4 (7%) patients with ophthalmic segment aneurysms had large infarcts involving the ICA territory died post-operatively. 1 patient, 74 years old developed an anterolateral wall myocardial infarction which was managed appropriately. Considering the GOS at discharge or at last follow-up, 44 (81%) patients had a good GOS and 10 (18.5%) patients had a poor GOS (Table 2). 4.2. Morbidity 1 patient who was operated under total circulatory cardiac arrest under hypothermia developed an operative site extradural hematoma in the immediate post-operative period due to improper reversal of coagulopathy necessitating surgery for evacuation of the same. 7 patients developed clinically significant limb weakness and 3 patients developed sensory or motor dysphasia. 5 patients developed SIADH post-operatively. 6 patients developed infarcts causing mass effect including the 4 patients who died. They required decompressive craniectomy for raised intracranial pressure caused by the infarcts. One patient with a non-dominant parietal MCA infarct and who also underwent a decompressive craniotomy developed a syndrome of the
trephined. His sensorium improved after replacement of bone flap. A patient with an ophthalmic segment aneurysm developed CSF rhinorrhoea due to a leak through the frontal sinus which was entered during craniotomy. He required re-exploration of the craniotomy and exteriorization of the frontal sinus. 4.3. Follow-up Of the 50 patients with a GOS ranging between 2 and 5, 43 were on follow-up for a mean period of 18.4 months (range 2 months–9 years). 40 of these patients on follow-up had post-operative imaging in the form of a DSA/MRA/CTA. 36 of these patients had their aneurysms excluded from the circulation. 2 patients (ophthalmic segment aneurysm and choroidal aneurysm) had a small residual neck. They were referred for endovascular coiling of the aneurysm at another center. 2 patients with a significant residual neck which was filling the aneurysm (ACOM and MCA aneurysm) underwent re-exploration and clipping of the aneurysm and subsequent angiograms showed that the aneurysms were well clipped. 3 patients declined radiological testing as they had other medical problems like polycythemia rubra, carcinoma breast and chronic renal failure which required proximate management of these pathologies.
Fig. 2. (A) Axial T2WI and (B) MR angiogram showing giant left MCA bifurcation aneurysm (C) DSA AP view showing no residual post-clipping.
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Fig. 3. (A) Coronal T2WI showing a (B) DSA lateral view showing a partially thrombosed distal right ACA aneurysm (C) DSA showing no residual post-clipping.
An analysis of the prevalence of post-operative complications in patient groups divided by demographics, aneurysm location and characteristics, and operative details (Table 3) showed that patients with age greater than 50 years (p = 0.045; OR 0.28, 95% CI 0.09–0.89), adverse intra-operative events (p = 0.015; OR 0.20,95% CI 0.06–0.69) and those with a documented infarction in the post-operative period (p < 0.001; OR 49.6,95% CI 8.64–284.6) had significantly higher post-operative morbidity than those younger than 50 years age and those without adverse intraoperative events or infarctions. The location of aneurysm (ophthalmic/paraclinoid vs other anterior circulation sites) did not return significant values for post-operative complications. Patients who suffered an intra-operative aneurysm rupture were shown to develop infarctions at a level of significance (p = 0.012; OR 0.19, 95% CI 0.05–0.66) than those without an intra-operative rupture. Table 4 highlights the analyzed patient outcome based on the GOS at last encounter. Patients who were younger than 50 years (OR 0.10, 95% CI 0.12–0.56), those without adverse intraoperative aneurysm rupture (OR 0.064, 95% CI 0.01–0.36) and WFNS SAH score of 1 or 2 had a better outcome than their older counterparts, those with adverse intra-operative events or higher WFNS SAH score (p = 0.009, 0.001. 0.031, respectively). The paired T-test showed that the mean age between the 2 groups was also found to be significant (p = 0.02). Table 5 which analyzes patient age and sex with respect to the location of the aneurysm and Fisher SAH grade at presentation did not return any significant values. Table 6 analyzes the significance of aneurysm characteristics, intra-operative events, mode of presentation, clinical grade and post-operative outcome with respect to aneurysm location in the patient population. Patients with non-ophthalmic/paraclinoid aneurysms had a significant lower incidence of adverse intraoperative events (p = 0.035; OR 0.26, 95% CI 0.07–0.86) than their ophthalmic counterparts. There was a significant association of presentation with SAH in these patients (p = 0.014; OR 0.23, 95% CI 0.071–0.076) in comparison with ophthalmic/paraclinoid aneurysm patients. Interestingly, there was a higher incidence of postoperative infarctions and morbidity in the ophthalmic/paraclinoid Table 2 Glasgow outcome score (GOS) at discharge or last follow-up. GOS
Number of patients
5 4 3 2 1
36 8 3 3 4
group than the ‘other’ anterior circulation group. However, the p values did not return statistical significance though the association was strong. Interestingly there was a higher occurrence of nonophthalmic aneurysms in male patients and an equal occurrence of aneurysms of both groups in female patients as noted in Table 5 (p = 0.052). The mean duration of temporary clip application in the good and bad outcome groups (Table 4) was not significantly different. Based on our sample size we used the penalized logistic regression model to study the effect of variables viz. patient demographics, aneurysm characteristics, surgical and post-operative data on final patient outcome. Out of the 10 variables listed in Table 4, the grouped age variable (coefficient value 2.763) was most influential on the GOS of the patient at follow-up. 5. Discussion This study elucidates the outcome of "pure surgical" clipping of aneurysms which have not been subjected to a multi-modality approach involving bypass surgery or endovascular intervention as part of the treatment option. Unfavorable outcome and mortality rates are higher in giant aneurysms and in aneurysms located in the posterior circulation [12]. However, outcome rates are trending upwards with lower mortality rates in the more recent studies analyzing outcomes of giant aneurysms and those located in the anterior circulation lesions [13]. The subset of very large and giant aneurysms of the anterior circulation has been generally more amenable to surgical exclusion from the parent circulation. 5.1. Presentation and time to surgery 37% of our cases involved the ophthalmic segment. This might be attributed to referral bias due to the complex nature and location of the aneurysm which probably required intervention at a tertiary center. Similarly, a large portion of the cases were in a good WFNS grade or Fisher CT grade which reflect symptomatology caused by mass effect or chronic headaches rather than SAH. There was considerable delay from the time of SAH to admission to our center for surgical management. Delayed presentation for treatment was attributed to; patient apathy towards symptoms like chronic headache, non-hemorrhagic symptoms causing mass effect or the search for an institute like ours which treats uninsured patients. A study on the outcome of clipping based on the time from symptomatology to surgical exercise, which would include patients with SAH was not possible as the delay in seeking treatment as noted in our patients would have negated the immediate morbidities of SAH and selected those who were
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Fig. 4. Right ICA DSA showing a giant ophthalmic segment aneurysm (A) pre and (B) post-clipping with no residual.
Table 3 Analysis of post-operative complications with respect to patient demographics, aneurysm characteristics, radiological findings and operative details. Post-op complications Absent (number of patients) Age 50 years 9 Presence of aneurysmal thrombus Yes 12 No 21 Temporary clip application Yes 22 No 11 Site of aneurysm Carotico-ophthalmic/ 9 paraclinoid 24 Other Temporary clip duration 10 min 9 Sex Male 19 Female 14 SAH (Bled vs unbled) Yes 20 No 13 Single ictus Yes 22 No 11 Fisher grade 1 or 2 21 3 or 4 12 Uneventful intra-operative period Yes 27 No 6 WFNS grade 1 or 2 33 3 or 4 0 Infarct on post-operative scan Yes 2 No 31 Intra-operative Post-op infarct aneurysm rupture present Yes 10 No 8
Present (number of patients)
P value
9 12
0.045
9 12
0.776
10 11
0.256
11
0.085
10 16 5
0.99
7 14
0.101
8 13
0.163
9 12
0.09
17 4
0.229
10 11
0.015
19 2
0.147
16 5 Post-op infarct absent 7 29
50 Age (years) 50 >50 Age (years) 50 >50 Age (years) 50 >50 Sex Male Female Sex Male Female Sex Male Female
Carotico-ophthalmic/paraclinoid 10 10 SAH (bled) 17 11 Fisher grade 1 or 2 24 14 WFNS grade 1 or 2 32 20 Carotico-ophthalmic/paraclinoid 6 14 SAH (bled) 15 13 Fisher grade 1 or 2 17 21
Other 23 11 Other (unbled) 16 10 Fisher grade 3 or 4 9 7 WFNS grade 3 or 4 1 1 Other 20 14 Other (unbled) 11 15 Fisher grade 3 or 4 9 7
0.253
0.99
0.762
0.99
0.052
0.43
0.554
No 16 Presence of aneurysm thrombus Yes 17 No 27 Temporary clip duration 10 min 12 Clip duration (minutes) 11 (sd Intra-operative rupture Yes 9 No 35 WFNS grade 1or 2 44 3 or 4 0
6 0.99 4 6 0.99 8 2 0.83 17.8)
9.8 (sd
16.3) 0.001
8 2 0.031 8 2
have separately reported an overall mortality rate of about 21.1% and a surgical mortality rate of 8.6% for giant aneurysms involving both anterior and posterior circulation [15,30]. Hauck et al. reported an overall mortality of 15%, 4% in patients younger than 50 years, and 22% in older patients operated for very large and giant aneurysms of the anterior circulation [9]. Of interest is the fact that the mentioned series had the advantage of extracranial to intracranial bypass performed in select cases. Our series did not benefit from this procedure. Poor surgical outcome from clipping of giant aneurysms has ranged between 20 and 30% with centers performing adjunct bypass and proximal artery occlusion or aneurysm trapping for a large number of these cases [19,31]. Bypass for giant aneurysm was performed in 54 of 141 cases (38%) especially with external carotid to MCA anastomosis performed in 25 patients with anterior circulation aneurysms [19]. In a metaanalysis Komotar reported a mortality rate of 9.6–37.9% and 7.4– 26.9% in giant posterior and anterior circulation aneurysms, respectively [13]. 5.4. Patient outcome
result of which, this procedure has slowly given way to proximal parent vessel trapping and bypass upstream of the aneurysm [8]. 5.3. Mortality rate Our series had a mortality of 7% all of which involved ophthalmic segment aneurysms that were unruptured. Surgical mortality rates for giant aneurysms vary from 4 to 21%, with an average of 10% [21,22]. In a series of 32 giant aneurysms which included both anterior and posterior circulation aneurysms, of which more than 80% had ruptured at the time of admission, Onuma and Suzuki reported a mortality rate of 20.8%, with an overall poor outcome in 37.5% of patients [23]. The mortality rates for patients with ruptured giant aneurysms of the anterior and posterior circulation reported in various series have ranged from 8 to 67%, whereas in series composed of patients with both unruptured and ruptured aneurysms, the mortality rate averages 15% [24–27]. Kato reported a mortality rate of 9% among 111 clipped anterior circulation aneurysms [28]. Kars reports a 10% mortality and zero morbidity in 10 operated large and giant anterior circulation aneurysms [29]. Pipegras and Simon and Vadja
Patients younger than 50 years of age had a better surgical outcome than those older than 50 years (p < 0.05), Hauck has shown similar results in patients in groups younger and older than 50 years [15]. The author also analyzed the outcome in ages above 50 years by dividing into groups each separated by 10 years. The risk of poor outcome increased by each decade and approached the risk of aneurysm rupture in the 60–69 age group. The risk of surgical intervention superseded the risk of rupture based on the ISUIA data in the 70 years and above age group [15]. This is because patients older than 50 years have other confounding factors affecting outcome; cardiovascular and endocrine co-morbidities which include and are not limited to diabetes mellitus, hypertension, altered renal function and respiratory reserve. Advanced age encompasses the effects of comorbidities, atherosclerotic changes in the vessel wall and post-operative hemodynamic changes which can adversely affect recovery for aneurysm surgery. This is validated in our study which shows that grouped age had the highest influence on patient outcome. Drake et al. in a study of 335 patients treated for anterior circulation giant aneurysm reported 18 mortalities and had 26
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Table 6 Analysis of aneurysm characteristics, intra-operative events, mode of presentation, clinical grade and post-operative outcome with respect to aneurysm location. MCA/ACOM/Ant. choroidal/DACA Infarct post-op No 26 8 Yes Temporary clip application Yes 21 No 13 Uneventful intra-op procedure Yes 27 No 7 Uneventful post-op period Yes 24 No 10 Temporary clip duration (min) 24 10 10 Presence of aneurysm thrombus Yes 15 19 No SAH (bled vs unbled) Yes 22 No 12 WFNS grade 1 or 2 33 3 or 4 1
C-ophthalmic/ paraclinoid
P value
10 10
0.073
11 9
0.775
10 10
0.035
9 11
0.085
16 4
0.533
6 14
0.391
6 14
0.014
19 1
0.99
near significance of post-operative adverse outcome in the ophthalmic group in comparison to the non-ophthalmic group (p = 0.08) could have been possibly reduced. Patients with a WFNS SAH score of 1or 2 had a better outcome than those with higher scores. Delayed presentation of patients with SAH who survived their icti would indirectly convert them into a category without vasospatic co-morbidities and relate them to the unruptured group. This would skew their outcome towards a favorable group even though SAH was recorded in them. Szmukda reported no significant difference in the mortality rates among surgically treated giant and small ICA aneurysms [22]. Khanna et al. proposed a grading system for unruptured aneurysms based on patient age, aneurysm size and location [37]. Based on the grading system (Grade 0 to grade VI) patients older than 40 years with complex large or giant aneurysms of the anterior circulation would be categorized to be grade III–V. In this study, successively higher poor outcome rates were recorded in the IV and V groups [37]. We did not compare the outcome of giant aneurysms with a matched number of aneurysms lesser than 2 cm in size as the control group would have been large in comparison to our study group. Similarly we did not compare outcome in relation to the coiled group as the number of patients in the giant aneurysm category who were subjected to endovascular coiling was low. 6. Conclusions
patients with poor outcome overall. The total calculated risk of an adverse outcome of 13% [32]. In our study, 8% of our patients on follow-up had aneurysms which persisted in the circulation and either required re-surgery or endovascular management. As a sub-group analysis, Velat et al. reported perioperative morbidity and mortality rates as 36% and 18.3%, respectively, in 11 surgically managed giant posterior communicating aneurysms and good clinical outcome in 5 of 6 (86%) patients available for followup [33]. Lownie et al. reported good surgical outcome in 75% of operated giant ACOM aneurysms in a series of 18 patients of which 16 who were on follow-up [34]. While analyzing surgical outcome of 80 ophthalmic segment aneurysms Nanda and Javalkar encountered 28 (33%) giant aneurysm and 40 (46%) large aneurysms. They reported no significant difference in surgical outcome between giant and non-giant ophthalmic segment aneurysms [35]. There are some limitations to this study. It does not take into account surgical intervention by a single operator, since it was a retrospective study. It also does not account for patient comorbidities. We also did not study outcome of patients older than 60 years, with a subgroup separated by 10 years as we had 8 patients 61 years or older. Though the adverse effect of postoperative infarction on outcome is statistically significance, it should be read with caution as it has a wide confidence interval. The usage of intra-operative Doppler to measure flow velocities in the early part of the series would have falsely indicated a good flow across a vessel distal to the site of aneurysm clipping. In fact, a high velocity would be indicative of blood flow in a vessel with compromised lumen. We have thus migrated to the use of indocyanine green to check for parent vessel compromise. We were also handicapped by the lack of stand-by EC-IC bypass surgery and combined surgical-endovascular management of some of the cases. This would have been advantageous in dealing with aneurysms on the proximal ICA especially paraclinoid/ ophthalmic segment aneurysms. New generation of flow diverters and stent/balloon assisted coiling are endovascular alternatives for management of skull base complex aneurysms [36]. The significant occurrence of intra-operative adverse events (p = 0.035), the fact that all mortalities were recorded in the ophthalmic group and the
This article evaluates outcome and complications in the highrisk proximal ICA and anterior circulation aneurysms which were managed by direct clipping. By using bypass techniques and indirect giant aneurysm occlusion, a surgeon can obviate the morbidity and mortality associated with direct giant aneurysm clipping or surgery under controlled hypothermic cardiac arrest. Clipping of proximal ICA aneurysms has high risk of intra-operative adverse events. Stand-alone clipping of ophthalmic segment aneurysms are associated with higher complication & morbidity rates and mortalities. Adjunct management techniques as highlighted above may be useful to avoid complications in these cases. A consideration of the natural history of ruptured and unruptured large and giant aneurysms is required in the elderly when surgery is contemplated as the only management option. Disclosure This article has not been submitted for publication to any other journal and has not been presented in conferences. There are no related articles published or submitted for publication. There is no conflict of interest arising from this article. The authors have not received any financial support in the form of grant from any source for preparation of this article or in the course of the study. The manuscript has been prepared per the guidelines laid down by our institute. References [1] Wiebers DO, Whisnant JP, Huston 3rd J. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103–10. [2] Wiebers DO. Unruptured intracranial aneurysms: natural history and clinical management. Update on the international study of unruptured intracranial aneurysms. Neuroimaging Clin N Am 2006;16:383–90. [3] Origitano TC, Anderson DE, Tarassoli Y, Reichman OH, al-Mefty O. Skull base approaches to complex cerebral aneurysms. Surg Neurol 1993;40:339–46. [4] Biondi A, Jean B, Vivas E, et al. Giant and large peripheral cerebral aneurysms: etiopathologic considerations, endovascular treatment, and long-term followup. AJNR Am J Neuroradiol 2006;27:1685–92. [5] Batjer HH, Samson DS. Causes of morbidity and mortality from surgery of aneurysms of the distal basilar artery. Neurosurgery 1989;25:904–16.
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[21] Sharma BS, Gupta A, Ahmad FU, Suri A, Mehta VS. Surgical management of giant intracranial aneurysms. Clin Neurol Neurosurg 2008;110:674–81. [22] Szmuda T, Sloniewski P. Early and long-term outcome of surgically treated giant internal carotid artery aneurysms – comparison with smaller aneurysms. Acta Neurochir (Wien) 2011;153:1611–9. [23] Onuma T, Suzuki J. Surgical treatment of giant intracranial aneurysms. J Neurosurg 1979;51:33–6. [24] Drake CG. Giant intracranial aneurysms: experience with surgical treatment in 174 patients. Clin Neurosurg 1979;26:12–95. [25] Sundt Jr TM, Piepgras DG, Fode NC, et al. Giant intracranial aneurysms. Clin Neurosurg 1991;37:116–54. [26] Symon L. Surgical experiences with giant intracranial aneurysms. Acta Neurochir 1992;118:53–8. [27] Whittle IR, Dorsch NW, Besser M. Giant intracranial aneurysms: diagnosis, management, and outcome. Surg Neurol 1984;21:218–30. [28] Kato Y, Sano H, Imizu S, et al. Surgical strategies for treatment of giant or large intracranial aneurysms: our experience with 139 cases. Minim Invasive Neurosurg 2003;46:339–43. [29] Kars HZ, Gurelik M. Clipping of large and giant aneurysms of anterior circulation. Turk Neurosurg 2011;21:53–8. [30] Symon L, Vajda J. Surgical experiences with giant intracranial aneurysms. J Neurosurg 1984;61:1009–28. [31] Choudhri O, Mukerji N, Steinberg GK. Combined endovascular and microsurgical management of complex cerebral aneurysms. Front Neurol 2013;4:108. [32] Drake CG. Evolution of intracranial aneurysm surgery. Can J Surg 1984;27:549– 55. [33] Velat GJ, Zabramski JM, Nakaji P, Spetzler RF. Surgical management of giant posterior communicating artery aneurysms. Neurosurgery 2012;71(1 Suppl Operative):43–50. [34] Lownie SP, Drake CG, Peerless SJ, Ferguson GG, Pelz DM. Clinical presentation and management of giant anterior communicating artery region aneurysms. J Neurosurg 2000;92:267–77. [35] Nanda A, Javalkar V. Microneurosurgical management of ophthalmic segment of the internal carotid artery aneurysms: single-surgeon operative experience from Louisiana State University, Shreveport. Neurosurgery 2011;68:355–70. [36] Darsaut TE, Guzman R, Marcellus ML, et al. Management of pediatric intracranial arteriovenous malformations: experience with multi-modality therapy. Neurosurgery 2011;69:540–56. [37] Khanna RK, Malik GM, Qureshi N. Predicting outcome following surgical treatment of unruptured intracranial aneurysms: a proposed grading system. J Neurosurg 1996;84:49–54.
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Surgical outcome of primary clipping for anterior circulation aneurysms of size 2 centimeters or larger Sunil V. Furtado *, Narayanam A. Saikiran, Sumit Thakar, Ravi Dadlani, Dilip Mohan, Saritha Aryan, Alangar S. Hegde Department of Neurosurgery, Sri Sathya Sai Institute Of Higher Medical Sciences, EPIP Area, Whitefield, Bangalore 560066, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 December 2013 Received in revised form 3 March 2014 Accepted 13 April 2014 Available online 22 April 2014
Background: Aneurysms of the anterior circulation larger than 2 cm have a complex relationship to the anterior skull base, requiring a multi-modality management approach. This retrospective study of 54 patients with such aneurysms who underwent clipping between 2001 and 2012 analyzes clinical and surgical data, aneurysm characteristics and correlates them with respect to the Glasgow outcome score at follow-up and immediate post-operative clinical status. Methods: Patients with an outcome score of 5 or 4 were categorized as “good", while those with score 3–1 were “poor”. Fisher’s exact test and paired T-test (p < 0.5) were used to test statistical significance for discrete and continuous variables respectively. Results: 44 (81.4%) patients had a good outcome. Patients with non-ophthalmic/paraclinoid aneurysms had significantly lower incidence of adverse intra-operative events (p = 0.035). Patients older than 50 years (p = 0.045), with adverse intra-operative events (p = 0.015) and post-operative infarction (p < 0.001) had a poor outcome compared to those younger than 50 years age and those without adverse intraoperative events or infarctions. The grouped age variable had maximum influence on patient outcome. Location and size of aneurysm did not have an overall impact on surgical outcome. There were 4 mortalities. Conclusions: Primary clipping of proximal non-cavernous aneurysms on the internal carotid artery is associated with adverse intra-operative events. A multi-modality treatment approach in these aneurysms should be individualized, more so in patients older than 50 years. ã 2014 Elsevier B.V. All rights reserved.
Keywords: Giant aneurysm Anterior circulation Clipping Intracranial hemorrhage SAH
1. Introduction Surgical approach to proximal large and giant anterior circulation aneurysms is challenged by their relationship to the skull base, cavernous sinus and cranial nerves in close proximity. The 5-year cumulative rupture rate for anterior circulation aneurysms of size 13–24 mm and 25 mm or greater is 14.5% and 40% respectively [1,2]. Two-thirds of giant aneurysms are diagnosed before rupture, mainly due to mass effect on cranial nerves, besides presenting with; seizures, repeated TIAs (transient ischemic attacks) or subarachnoid hemorrhage [3]. Flow-related large and giant aneurysms are usually located at the branching regions on the parent vessel [4].
* Corresponding author at: Sri Sathya Sai Institute of Higher Medical Sciences, Department of Neurosurgery, EPIP Area, Whitefield, Bangalore 560066, India. Tel.: +91 80 28416837. E-mail address: [email protected] (S.V. Furtado). http://dx.doi.org/10.1016/j.clineuro.2014.04.012 0303-8467/ ã 2014 Elsevier B.V. All rights reserved.
There have been many advances in the exclusion of large and giant aneurysms from the native circulation since 1885 when Horsley first recorded surgical management (by proximal carotid ligation) of a giant aneurysm located in the pre-cavernous segment of the ICA [3,5,6]. Given the complexity of these aneurysms, there is a high incidence of post-operative morbidity and death associated with surgical exclusion of these aneurysms from the circulation. The risks often exceed the risk of subarachnoid hemorrhage (SAH) from them [1]. This paper addresses the risks associated with primary clipping of aneurysms larger than 2 cm, located in the anterior circulation. The use of microsurgical, endovascular modalities and adjuncts like intra-operative neuromonitoring and blood-flow studies provide a multi-modality approach to treat this complex pathology [7,8]. 2. Materials and methods This retrospective study comprised patients with anterior circulation aneurysms, 2 cm or more in size. These aneurysms are
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categorized as very large and giant aneurysms of the anterior circulation [9]. Over a twelve-year period between January 2001 and June 2012, there were 54 such aneurysms operated and constituted 7.2% of operated aneurysm cases. Of the patients, 26 were male and 28 female, with a mean age of 45.1 years. Other parameters like; patient demographics, symptom at presentation, clinical signs, World federation of neurological societies (WFNS) subarachnoid (SAH) grade at first presentation and functional status at follow-up were mined from the hospital electronic patient database once the subset of aneurysm patients was identified. Radiological images were obtained for review in all cases from the Synapse PACS (Fujifilm Medical Systems, Stamford, CT, USA) system and were used to calculate the size and location of aneurysm and post-surgical aneurysm status. Intra-operative details regarding usage of temporary clip and the duration of temporary clip usage, intra-operative aneurysm rupture, number and configuration of permanent clip used were obtained from the operative notes and video archives. Data were entered in an Excel spreadsheet (Microsoft Inc.,) and analyzed using SPSS version 17 for Windows (SPSS Inc., Chicago, IL). Patients were divided into two groups; good- Glasgow outcome score (GOS) 5 and 4 and poor (3–1) outcome groups, based on their clinical status at the last follow-up visit. Fisher’s exact test two-tailed (p < 0.05) was used to check correlation of clinical outcome with demographic, intra-operative surgical maneuvers and adverse events like aneurysm rupture, clinico-radiological factors pre-and post-surgery. Means and standard deviations were computed for continuous variables. The paired T-test was used to compare differences in ratios between the good and poor outcome groups. 3. Results 3.1. Presentation 28 patients primarily presented with subarachnoid hemorrhage (SAH), 2 with a temporal parenchymal bleed from middle cerebral artery (MCA) aneurysm, 9 presented with headaches with no recorded sub-arachnoid bleed on radiology, 7 had visual abnormalities, 4 had seizures, 3 had oculomotor nerve palsies and 1 had a subdural hematoma. Out of the patients with SAH, 23 had a single ictus. 4 patients bled twice and 1 patient had 3 icti. In addition, 2 patients with SAH also had post-bleed seizures and 2 patients later developed abducens nerve palsy secondary to hydrocephalus. The patients presented between 1 day and 4 years after ictus (median 30 days). Forty-eight patients were in WFNS SAH grade 1 at presentation, 4 in grade 2 and 1 each in grade 3 and 4. On computed tomography (CT) or magnetic resonance (MR) evaluation at the hospital at first presentation and applying the Fisher score for SAH; 32 exhibited Fisher grade 1, 7 were in grade 2,12 had Fisher grade 3 score and 3 had Fisher grade 4 score. Hydrocephalus was seen in 4 patients pre-operatively. A total of 10 patients required an external ventricular drain in the perioperative period (4 pre-operative and 6 post-operative). A total of 6 patients required a ventriculo-peritoneal shunt post-operatively, which included 3 patients from the pre-operative hydrocephalus group. Infarcts were seen pre-operatively in 3 patients involving the parietal MCA territory in 1 patient and distal anterior cerebral artery (DACA) i.e. A4 territory in 2 patients. Calcification in the vessel wall was documented in 5 patients and an intra-aneurysmal thrombus was noted in 21 patients. 21 patients underwent an angiogram to delineate the aneurysm in relation to the skull base. 3.2. Aneurysm characteristics The location of aneurysms is provided in Table 1. Ophthalmic segment aneurysms had a higher incidence (20 cases), followed by
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middle cerebral artery bifurcation (12 cases) and anterior communicating artery aneurysms (11 cases). There was a case of giant A1 segment aneurysm and 2 cases of giant distal anterior cerebral artery aneurysm. Giant aneurysms in the A1 segment and pericallosal region are rare with only a dozen reported cases in each either region [10,11]. These aneurysms are usually associated with arterial anomalies like A1 fenestration, azygos anterior cerebral artery or trauma as in the case of DACA aneurysms, which our patients did not exhibit. The average size of the aneurysms was 2.20 cm (median 2.6; SD 1.10). Two patients with ophthalmic segment aneurysms had small aneurysms in another location (opposite ophthalmic segment and anterior communicating (ACOM) aneurysm). A patient with a posterior communicating segment (PCOM) aneurysm had a Spetzler–Martin grade 1 frontal arterio-venous malformation. Balloon occlusion tests were performed in 49 patients to test the patency of the communicating system and document cross flow. 3.3. Surgery 46 patients with aneurysms underwent a pterional craniotomy and clipping of their anterior circulation aneurysm. 5 patients with ophthalmic segment aneurysms underwent an orbito-zygomatic approach and 2 patients with DACA aneurysms underwent a pericoronal parasagittal craniotomy and 1 patient with a cavernous segment underwent ligation of the cervical internal carotid artery (ICA) under local anesthesia following temporary occlusion of the cervical ICA under hypotensive condition. 52 of the remaining aneurysms were clipped primarily and a giant A1 segment aneurysm was trapped on the A1 segment as the neck was atherosclerotic and the aneurysm could not be clipped with the available clips. Yasargil titanium aneurysm clips (Aesculap Inc., PA) were used in all surgeries. 3 cases (Giant ACOM and 2 ophthalmic segment aneurysms) were operated under total circulatory cardiac arrest under hypothermic conditions. 14 patients with ophthalmic segment aneurysms required drilling of the anterior clinoid process and the roof of optic canal. A temporary clip was used in 32 cases for a mean duration of 5.46 min (median 4 min, range 1–28 min). 37 patients did not have any documented adverse intraoperative events in the operative records which included aneurysm rupture, clip adjustment due to compromise of perforator vessels or communicating vessels of the circle of Willis. Figs. 1–4 show well clipped ACOM, MCA and ophthalmic segment aneurysms in the series. 4. Outcome 4.1. Immediate post-operative 40 (74%) patients were neurologically intact immediately after surgery. 18 (33%) patients had infarcts documented in their postoperative CT or MR images, out of which 10 (18.5%) infarcts involved eloquent areas causing clinical weakness, alteration in sensorium or dysphasia. 3 patients in this group (2 patients with an internal capsular and 1 with a parietal lobar MCA infarct) Table 1 Location of aneurysm. Ophthalmic segment aneurysm Middle cerebral artery aneurysm Anterior communicating artery aneurysm Posterior communicating segment aneurysm Anterior choroidal segment aneurysm Distal anterior cerebral artery aneurysm Anterior cerebral artery aneurysm (A1) Cavernous/clinoid segment ICA aneurysm
20 12 11 5 2 2 1 1
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Fig. 1. DSA anteroposterior (AP) view (A) 2.3 cm ACOM aneurysm (B) with no residual post-clipping.
showed improvement in their motor deficit and had a good GOS at last follow-up. 4 (7%) patients with ophthalmic segment aneurysms had large infarcts involving the ICA territory died post-operatively. 1 patient, 74 years old developed an anterolateral wall myocardial infarction which was managed appropriately. Considering the GOS at discharge or at last follow-up, 44 (81%) patients had a good GOS and 10 (18.5%) patients had a poor GOS (Table 2). 4.2. Morbidity 1 patient who was operated under total circulatory cardiac arrest under hypothermia developed an operative site extradural hematoma in the immediate post-operative period due to improper reversal of coagulopathy necessitating surgery for evacuation of the same. 7 patients developed clinically significant limb weakness and 3 patients developed sensory or motor dysphasia. 5 patients developed SIADH post-operatively. 6 patients developed infarcts causing mass effect including the 4 patients who died. They required decompressive craniectomy for raised intracranial pressure caused by the infarcts. One patient with a non-dominant parietal MCA infarct and who also underwent a decompressive craniotomy developed a syndrome of the
trephined. His sensorium improved after replacement of bone flap. A patient with an ophthalmic segment aneurysm developed CSF rhinorrhoea due to a leak through the frontal sinus which was entered during craniotomy. He required re-exploration of the craniotomy and exteriorization of the frontal sinus. 4.3. Follow-up Of the 50 patients with a GOS ranging between 2 and 5, 43 were on follow-up for a mean period of 18.4 months (range 2 months–9 years). 40 of these patients on follow-up had post-operative imaging in the form of a DSA/MRA/CTA. 36 of these patients had their aneurysms excluded from the circulation. 2 patients (ophthalmic segment aneurysm and choroidal aneurysm) had a small residual neck. They were referred for endovascular coiling of the aneurysm at another center. 2 patients with a significant residual neck which was filling the aneurysm (ACOM and MCA aneurysm) underwent re-exploration and clipping of the aneurysm and subsequent angiograms showed that the aneurysms were well clipped. 3 patients declined radiological testing as they had other medical problems like polycythemia rubra, carcinoma breast and chronic renal failure which required proximate management of these pathologies.
Fig. 2. (A) Axial T2WI and (B) MR angiogram showing giant left MCA bifurcation aneurysm (C) DSA AP view showing no residual post-clipping.
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Fig. 3. (A) Coronal T2WI showing a (B) DSA lateral view showing a partially thrombosed distal right ACA aneurysm (C) DSA showing no residual post-clipping.
An analysis of the prevalence of post-operative complications in patient groups divided by demographics, aneurysm location and characteristics, and operative details (Table 3) showed that patients with age greater than 50 years (p = 0.045; OR 0.28, 95% CI 0.09–0.89), adverse intra-operative events (p = 0.015; OR 0.20,95% CI 0.06–0.69) and those with a documented infarction in the post-operative period (p < 0.001; OR 49.6,95% CI 8.64–284.6) had significantly higher post-operative morbidity than those younger than 50 years age and those without adverse intraoperative events or infarctions. The location of aneurysm (ophthalmic/paraclinoid vs other anterior circulation sites) did not return significant values for post-operative complications. Patients who suffered an intra-operative aneurysm rupture were shown to develop infarctions at a level of significance (p = 0.012; OR 0.19, 95% CI 0.05–0.66) than those without an intra-operative rupture. Table 4 highlights the analyzed patient outcome based on the GOS at last encounter. Patients who were younger than 50 years (OR 0.10, 95% CI 0.12–0.56), those without adverse intraoperative aneurysm rupture (OR 0.064, 95% CI 0.01–0.36) and WFNS SAH score of 1 or 2 had a better outcome than their older counterparts, those with adverse intra-operative events or higher WFNS SAH score (p = 0.009, 0.001. 0.031, respectively). The paired T-test showed that the mean age between the 2 groups was also found to be significant (p = 0.02). Table 5 which analyzes patient age and sex with respect to the location of the aneurysm and Fisher SAH grade at presentation did not return any significant values. Table 6 analyzes the significance of aneurysm characteristics, intra-operative events, mode of presentation, clinical grade and post-operative outcome with respect to aneurysm location in the patient population. Patients with non-ophthalmic/paraclinoid aneurysms had a significant lower incidence of adverse intraoperative events (p = 0.035; OR 0.26, 95% CI 0.07–0.86) than their ophthalmic counterparts. There was a significant association of presentation with SAH in these patients (p = 0.014; OR 0.23, 95% CI 0.071–0.076) in comparison with ophthalmic/paraclinoid aneurysm patients. Interestingly, there was a higher incidence of postoperative infarctions and morbidity in the ophthalmic/paraclinoid Table 2 Glasgow outcome score (GOS) at discharge or last follow-up. GOS
Number of patients
5 4 3 2 1
36 8 3 3 4
group than the ‘other’ anterior circulation group. However, the p values did not return statistical significance though the association was strong. Interestingly there was a higher occurrence of nonophthalmic aneurysms in male patients and an equal occurrence of aneurysms of both groups in female patients as noted in Table 5 (p = 0.052). The mean duration of temporary clip application in the good and bad outcome groups (Table 4) was not significantly different. Based on our sample size we used the penalized logistic regression model to study the effect of variables viz. patient demographics, aneurysm characteristics, surgical and post-operative data on final patient outcome. Out of the 10 variables listed in Table 4, the grouped age variable (coefficient value 2.763) was most influential on the GOS of the patient at follow-up. 5. Discussion This study elucidates the outcome of "pure surgical" clipping of aneurysms which have not been subjected to a multi-modality approach involving bypass surgery or endovascular intervention as part of the treatment option. Unfavorable outcome and mortality rates are higher in giant aneurysms and in aneurysms located in the posterior circulation [12]. However, outcome rates are trending upwards with lower mortality rates in the more recent studies analyzing outcomes of giant aneurysms and those located in the anterior circulation lesions [13]. The subset of very large and giant aneurysms of the anterior circulation has been generally more amenable to surgical exclusion from the parent circulation. 5.1. Presentation and time to surgery 37% of our cases involved the ophthalmic segment. This might be attributed to referral bias due to the complex nature and location of the aneurysm which probably required intervention at a tertiary center. Similarly, a large portion of the cases were in a good WFNS grade or Fisher CT grade which reflect symptomatology caused by mass effect or chronic headaches rather than SAH. There was considerable delay from the time of SAH to admission to our center for surgical management. Delayed presentation for treatment was attributed to; patient apathy towards symptoms like chronic headache, non-hemorrhagic symptoms causing mass effect or the search for an institute like ours which treats uninsured patients. A study on the outcome of clipping based on the time from symptomatology to surgical exercise, which would include patients with SAH was not possible as the delay in seeking treatment as noted in our patients would have negated the immediate morbidities of SAH and selected those who were
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Fig. 4. Right ICA DSA showing a giant ophthalmic segment aneurysm (A) pre and (B) post-clipping with no residual.
Table 3 Analysis of post-operative complications with respect to patient demographics, aneurysm characteristics, radiological findings and operative details. Post-op complications Absent (number of patients) Age 50 years 9 Presence of aneurysmal thrombus Yes 12 No 21 Temporary clip application Yes 22 No 11 Site of aneurysm Carotico-ophthalmic/ 9 paraclinoid 24 Other Temporary clip duration 10 min 9 Sex Male 19 Female 14 SAH (Bled vs unbled) Yes 20 No 13 Single ictus Yes 22 No 11 Fisher grade 1 or 2 21 3 or 4 12 Uneventful intra-operative period Yes 27 No 6 WFNS grade 1 or 2 33 3 or 4 0 Infarct on post-operative scan Yes 2 No 31 Intra-operative Post-op infarct aneurysm rupture present Yes 10 No 8
Present (number of patients)
P value
9 12
0.045
9 12
0.776
10 11
0.256
11
0.085
10 16 5
0.99
7 14
0.101
8 13
0.163
9 12
0.09
17 4
0.229
10 11
0.015
19 2
0.147
16 5 Post-op infarct absent 7 29
50 Age (years) 50 >50 Age (years) 50 >50 Age (years) 50 >50 Sex Male Female Sex Male Female Sex Male Female
Carotico-ophthalmic/paraclinoid 10 10 SAH (bled) 17 11 Fisher grade 1 or 2 24 14 WFNS grade 1 or 2 32 20 Carotico-ophthalmic/paraclinoid 6 14 SAH (bled) 15 13 Fisher grade 1 or 2 17 21
Other 23 11 Other (unbled) 16 10 Fisher grade 3 or 4 9 7 WFNS grade 3 or 4 1 1 Other 20 14 Other (unbled) 11 15 Fisher grade 3 or 4 9 7
0.253
0.99
0.762
0.99
0.052
0.43
0.554
No 16 Presence of aneurysm thrombus Yes 17 No 27 Temporary clip duration 10 min 12 Clip duration (minutes) 11 (sd Intra-operative rupture Yes 9 No 35 WFNS grade 1or 2 44 3 or 4 0
6 0.99 4 6 0.99 8 2 0.83 17.8)
9.8 (sd
16.3) 0.001
8 2 0.031 8 2
have separately reported an overall mortality rate of about 21.1% and a surgical mortality rate of 8.6% for giant aneurysms involving both anterior and posterior circulation [15,30]. Hauck et al. reported an overall mortality of 15%, 4% in patients younger than 50 years, and 22% in older patients operated for very large and giant aneurysms of the anterior circulation [9]. Of interest is the fact that the mentioned series had the advantage of extracranial to intracranial bypass performed in select cases. Our series did not benefit from this procedure. Poor surgical outcome from clipping of giant aneurysms has ranged between 20 and 30% with centers performing adjunct bypass and proximal artery occlusion or aneurysm trapping for a large number of these cases [19,31]. Bypass for giant aneurysm was performed in 54 of 141 cases (38%) especially with external carotid to MCA anastomosis performed in 25 patients with anterior circulation aneurysms [19]. In a metaanalysis Komotar reported a mortality rate of 9.6–37.9% and 7.4– 26.9% in giant posterior and anterior circulation aneurysms, respectively [13]. 5.4. Patient outcome
result of which, this procedure has slowly given way to proximal parent vessel trapping and bypass upstream of the aneurysm [8]. 5.3. Mortality rate Our series had a mortality of 7% all of which involved ophthalmic segment aneurysms that were unruptured. Surgical mortality rates for giant aneurysms vary from 4 to 21%, with an average of 10% [21,22]. In a series of 32 giant aneurysms which included both anterior and posterior circulation aneurysms, of which more than 80% had ruptured at the time of admission, Onuma and Suzuki reported a mortality rate of 20.8%, with an overall poor outcome in 37.5% of patients [23]. The mortality rates for patients with ruptured giant aneurysms of the anterior and posterior circulation reported in various series have ranged from 8 to 67%, whereas in series composed of patients with both unruptured and ruptured aneurysms, the mortality rate averages 15% [24–27]. Kato reported a mortality rate of 9% among 111 clipped anterior circulation aneurysms [28]. Kars reports a 10% mortality and zero morbidity in 10 operated large and giant anterior circulation aneurysms [29]. Pipegras and Simon and Vadja
Patients younger than 50 years of age had a better surgical outcome than those older than 50 years (p < 0.05), Hauck has shown similar results in patients in groups younger and older than 50 years [15]. The author also analyzed the outcome in ages above 50 years by dividing into groups each separated by 10 years. The risk of poor outcome increased by each decade and approached the risk of aneurysm rupture in the 60–69 age group. The risk of surgical intervention superseded the risk of rupture based on the ISUIA data in the 70 years and above age group [15]. This is because patients older than 50 years have other confounding factors affecting outcome; cardiovascular and endocrine co-morbidities which include and are not limited to diabetes mellitus, hypertension, altered renal function and respiratory reserve. Advanced age encompasses the effects of comorbidities, atherosclerotic changes in the vessel wall and post-operative hemodynamic changes which can adversely affect recovery for aneurysm surgery. This is validated in our study which shows that grouped age had the highest influence on patient outcome. Drake et al. in a study of 335 patients treated for anterior circulation giant aneurysm reported 18 mortalities and had 26
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Table 6 Analysis of aneurysm characteristics, intra-operative events, mode of presentation, clinical grade and post-operative outcome with respect to aneurysm location. MCA/ACOM/Ant. choroidal/DACA Infarct post-op No 26 8 Yes Temporary clip application Yes 21 No 13 Uneventful intra-op procedure Yes 27 No 7 Uneventful post-op period Yes 24 No 10 Temporary clip duration (min) 24 10 10 Presence of aneurysm thrombus Yes 15 19 No SAH (bled vs unbled) Yes 22 No 12 WFNS grade 1 or 2 33 3 or 4 1
C-ophthalmic/ paraclinoid
P value
10 10
0.073
11 9
0.775
10 10
0.035
9 11
0.085
16 4
0.533
6 14
0.391
6 14
0.014
19 1
0.99
near significance of post-operative adverse outcome in the ophthalmic group in comparison to the non-ophthalmic group (p = 0.08) could have been possibly reduced. Patients with a WFNS SAH score of 1or 2 had a better outcome than those with higher scores. Delayed presentation of patients with SAH who survived their icti would indirectly convert them into a category without vasospatic co-morbidities and relate them to the unruptured group. This would skew their outcome towards a favorable group even though SAH was recorded in them. Szmukda reported no significant difference in the mortality rates among surgically treated giant and small ICA aneurysms [22]. Khanna et al. proposed a grading system for unruptured aneurysms based on patient age, aneurysm size and location [37]. Based on the grading system (Grade 0 to grade VI) patients older than 40 years with complex large or giant aneurysms of the anterior circulation would be categorized to be grade III–V. In this study, successively higher poor outcome rates were recorded in the IV and V groups [37]. We did not compare the outcome of giant aneurysms with a matched number of aneurysms lesser than 2 cm in size as the control group would have been large in comparison to our study group. Similarly we did not compare outcome in relation to the coiled group as the number of patients in the giant aneurysm category who were subjected to endovascular coiling was low. 6. Conclusions
patients with poor outcome overall. The total calculated risk of an adverse outcome of 13% [32]. In our study, 8% of our patients on follow-up had aneurysms which persisted in the circulation and either required re-surgery or endovascular management. As a sub-group analysis, Velat et al. reported perioperative morbidity and mortality rates as 36% and 18.3%, respectively, in 11 surgically managed giant posterior communicating aneurysms and good clinical outcome in 5 of 6 (86%) patients available for followup [33]. Lownie et al. reported good surgical outcome in 75% of operated giant ACOM aneurysms in a series of 18 patients of which 16 who were on follow-up [34]. While analyzing surgical outcome of 80 ophthalmic segment aneurysms Nanda and Javalkar encountered 28 (33%) giant aneurysm and 40 (46%) large aneurysms. They reported no significant difference in surgical outcome between giant and non-giant ophthalmic segment aneurysms [35]. There are some limitations to this study. It does not take into account surgical intervention by a single operator, since it was a retrospective study. It also does not account for patient comorbidities. We also did not study outcome of patients older than 60 years, with a subgroup separated by 10 years as we had 8 patients 61 years or older. Though the adverse effect of postoperative infarction on outcome is statistically significance, it should be read with caution as it has a wide confidence interval. The usage of intra-operative Doppler to measure flow velocities in the early part of the series would have falsely indicated a good flow across a vessel distal to the site of aneurysm clipping. In fact, a high velocity would be indicative of blood flow in a vessel with compromised lumen. We have thus migrated to the use of indocyanine green to check for parent vessel compromise. We were also handicapped by the lack of stand-by EC-IC bypass surgery and combined surgical-endovascular management of some of the cases. This would have been advantageous in dealing with aneurysms on the proximal ICA especially paraclinoid/ ophthalmic segment aneurysms. New generation of flow diverters and stent/balloon assisted coiling are endovascular alternatives for management of skull base complex aneurysms [36]. The significant occurrence of intra-operative adverse events (p = 0.035), the fact that all mortalities were recorded in the ophthalmic group and the
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