Outcome Determinant of Patients Following Microsurgical Clipping of Ruptured Intracranial Aneurysms

Abstract

Objectives Numerous factors can influence patient outcomes following microsurgical clipping of intracranial aneurysms (IAs). Some unique factors, such as aneurysm surgery during the COVID-19 pandemic, also play a role. This study aims to evaluate outcomes in patients with ruptured IAs undergoing microsurgical clipping and identify predictors for both immediate and long-term prognosis.

Materials and Methods This is a retrospective study with prospectively collected data of 500 patients with ruptured aneurysms undergoing microsurgical clipping over a period of 10 years (April 2011–November 2022). The follow-up period ranged from 2 to 10 years, and clinical outcomes were evaluated using the Glasgow Outcome Scale (GOS). Data were analyzed using STATA version 3.10. Logistic regression was used to calculate p-values, with a significance level of p < 0.05.

Results Among 500 patients treated for ruptured IAs, 169 were males and 331 were females, with a median age of 53 years. Postoperative vasospasm was a major predictor of worse outcomes at discharge (p < 0.001), 6 months (p < 0.001), 1 year (p < 0.001), 5 years (p = 0.014), and 10 years (p = 0.006). Patients treated during the COVID-19 pandemic had worse outcomes at 6 months (p < 0.001) and 1 year (p = 0.001).

Conclusion Postoperative vasospasm, intraoperative rupture, and the COVID-19 pandemic were the most important predictors of worse outcomes. Factors such as age, hospital type, Miller Fisher grade, alcohol abuse, diabetes, aneurysm multiplicity, aneurysm size, neck size, ethnicity, hydrocephalus, brain retraction, and lamina terminalis fenestration did not significantly influence the outcomes.

Keywords

aneurysm - ruptured - intracranial aneurysm - microsurgery - subarachnoid hemorrhage - Glasgow Outcome Scale

Introduction

Rebleeding is a serious complication of untreated ruptured intracranial aneurysms (IAs), causing 50 to 60% mortality,[1] [2] [3] which happens in 8 to 23% of patients with ruptured aneurysm within the first 72 hours of ictus.[2] To prevent this, ruptured aneurysms require prompt treatment. Microsurgical clipping and endovascular procedures are two effective treatment modalities or combination of both.[4] [5] While endovascular techniques have rapidly advanced and are increasingly utilized over the past three decades, both endovascular and microsurgical approaches have distinct indications, advantages, and disadvantages. Microsurgical clipping remains a crucial treatment option, particularly in developing countries where resource limitations, including financial constraints, a shortage of trained neurointerventionists, and limited access to endovascular services, may favor this approach.

Patient outcomes after microsurgical clipping for ruptured IAs are influenced by a multitude of factors. Previous studies have investigated the impact of patient demographics (age, sex), comorbidities (diabetes mellitus, hypertension, smoking, alcohol abuse), aneurysm characteristics (location, size, neck size, multiplicity), perioperative factors (timing of surgery, Hunt and Hess (H&H) grade, modified Fisher grade, pre- and postoperative hematoma, temporary parent vessel occlusion during clipping), and surgical volume.[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] This study focuses on identifying the key risk factors among those previously studied that affect patient outcomes after microsurgical clipping of ruptured IAs. Specifically, we will investigate the influence of specific factors here, for example, hydrocephalus, lamina terminalis fenestration (LTF), use of brain retractors, ethnicity, types of hospital (government/private), warning leak, and COVID-19 pandemic.

Materials and Methods

Patient Population

This retrospective study with prospectively collected data was approved by the institutional review board of our institute. Between April 2011 and November 2022, 556 patients underwent microsurgical clipping for ruptured IAs. Of these, 500 patients met our inclusion criteria and were included in the study. Patient demographics, clinical and surgical details, postoperative events, surgical outcomes, and follow-up data were extracted from our electronic data system, SUKRA—a hospital information management system. Imaging data were retrieved from the picture archiving and communication system. All patients who underwent microsurgical clipping for ruptured IAs were included in this study. Patients whose aneurysms were treated with wrapping, trapping, or bypass surgery were excluded, as were those with untreated or unruptured aneurysms, those treated with endovascular procedures, pediatric patients, and those lost to follow-up.

Surgical Techniques

All ruptured anterior circulation aneurysms (ACAs) were clipped via a pterional approach, except for distal anterior cerebral artery aneurysms, which were approached via an anterior interhemispheric route. Intradural anterior clinoidectomy was performed before clipping the supraclinoid, ophthalmic, and superior hypophyseal aneurysms to expose the neck aneurysm and proximal internal carotid artery (ICA).

Basilar artery (BA), superior cerebellar artery–basilar artery (SCA-BA), and P1 and P2 segment aneurysms of the posterior cerebral artery (PCA) were addressed via either pterional or subtemporal approaches. P3–P4 segment PCA aneurysms were clipped via a posterior occipital interhemispheric approach. Vertebral artery–posterior inferior cerebellar artery (VA-PICA) aneurysms were secured via a lateral suboccipital route, and distal PICA aneurysms were approached via a midline suboccipital route.

Intraoperative temporary clips were applied to the proximal parent artery in cases of intraoperative rupture (IOR) or if the aneurysms were complex, large, or giant. Temporary occlusion times ranged from 1 to 5 minutes (repeated as necessary). Indocyanine green videography and transcranial Doppler were routinely used before and after clipping. An LTF was performed in all cases of ruptured ACA with intraventricular hemorrhage, hydrocephalus, or evolving hydrocephalus.

Radiological Studies

For all suspected cases of aneurysmal subarachnoid hemorrhage (aSAH), an urgent noncontrast computed tomography (CT) scan of the head was the initial investigation of choice. Lumbar puncture and cerebrospinal fluid analysis were performed in the few cases with normal CT findings. A CT angiogram of the head was the preferred diagnostic study for patients with aSAH. Cerebral digital subtraction angiography was recommended if the CT angiogram was normal or if a large, giant, or complex aneurysm was suspected. Postoperatively, all patients underwent cerebral CT angiography to assess the degree of cerebral vasospasm and aneurysm occlusion. Transcranial Doppler ultrasound was routinely used for the first few postoperative days to assess blood flow velocity in major cerebral vessels and rule out vasospasm.

Data Analysis

H&H clinical grade was dichotomized into low (1–3) and high (4–5) grades. Modified Fisher grade was similarly divided into low (0–2) and high (3–4) grades. Age was categorized into cohorts of less than 40 and ≥40 years. Outcome, measured by the Glasgow Outcome Scale (GOS), was dichotomized into favorable (4–5) and unfavorable (1–3) outcomes. GOS was analyzed at discharge, 6 months, and 1, 5, and 10 years postoperatively. Data were analyzed using STATA version 3.10. Logistic regression was used to calculate p-values, with a significance level of p < 0.05.

Results

Over 10 years, 556 patients underwent surgery for ruptured IAs, but only 500 met the inclusion criteria for this study. There were 169 male and 331 female patients, with a male-to-female ratio of 0.51 ([Fig. 1]). The median age was 53 years. Ninety percent of aneurysms were located in the anterior circulation. On admission, 77.4% of patients presented with low H&H grades (0–3), while 22.6% had high grades (4–5). Similarly, CT scans revealed low modified Fisher grades (0–2) in 28.8% of patients and high grades (3–4) in 71.8% patients. At discharge, several factors significantly impacted outcomes after surgical clipping: sex (p = 0.037), aneurysm location (p = 0.034), H&H grade (p < 0.001), smoking status (p = 0.018), timing of surgery (p = 0.044), postoperative vasospasm (p < 0.001), and the COVID-19 pandemic (p < 0.001). At the 6-month follow-up, significant factors influencing poor outcomes included aneurysm location (p = 0.013), H&H grade (p < 0.001), smoking status (p = 0.032), postoperative vasospasm (p < 0.001), and the COVID-19 pandemic (p < 0.001). At 1 year, significant factors were H&H grade (p = 0.012), hypertension (p = 0.014), IOR (p = 0.005), and postoperative vasospasm (p < 0.001). At 5 years, only IOR (p < 0.001) and postoperative vasospasm (p = 0.014) remained significant. At 10 years, only IOR (p = 0.006) was a significant determinant of worse outcomes ([Tables 1] [2] [3] [4] [5] [6] [7] [8] [9]). At discharge, only 77% of patients had favorable outcomes. However, patient outcomes continued to improve at subsequent follow-ups: 1 year (85.4%), 3 years (90.4%), 5 years (95.5%), and 10 years (96.8%). This indicates that even if immediate postoperative outcomes were not promising, many patients continued to improve over time ([Table 3]).

Fig. 1 Pie chart depicting the male-to-female ratio of 500 patients treated for ruptured intracranial aneurysms.

Table 1 Demographic, clinical, radiological, surgical characteristics, and functional outcome (Glasgow Outcome Scale [GOS]) of patients after microsurgical clipping at discharge and subsequent follow up

Variable	No. of patient (%)	Follow-up
		At discharge (p-Value)	6 mo (p-Value)	1 y (p-Value)	5 y (p-Value)	10 y (p-Value)
No. of patients	500
Age		0.068	0.083	0.454	0.293	0.823
Median age	53
Age >40 y	93 (18.6)
Age ≤40 y	407 (81.4)
Sex
Male	169 (33.8)	0.037	0.067	0.080	0.250	0.458
Female	331 (66.2)
Sex ratio (male/female)	0.5106
Ethnicity
Male, Mongol	36 (30.77)	0.182	0.117	0.011	0.767	0.933
Female, Mongol	81 (69.23)
Male, Aryan	133 (34.73)
Female, Aryan	250 (65.27)
Hospital
Government	293 (59.8)	0.703	0.717	0.265	0.993	0.336
Private	197 (40.2)
Aneurysm location
Anterior circulation	450 (90)	0.034	0.013	0.168	0.091	0.912
Posterior circulation	50 (10)
Hunt and Hess grade
0–3: low grade	387 (77.4)	0.000	0.000	0.012	0.339	0.792
4–5: high grade	113 (22.6)
Miller Fisher grade
0–2: low grade	141 (28.2)	0.067	0.211	0.311	0.338	0.351
3–4: high grade	359 (71.8)

Table 2 Demographic, clinical, radiological, surgical characteristics, and functional outcome (Glasgow Outcome Scale [GOS]) of patients after microsurgical clipping at discharge and subsequent follow-up

Variable	No. of patient (%)	Follow-up
		At discharge (p-Value)	6 mo (p-Value)	1 y (p-Value)	5 y (p-Value)	10 y (p-Value)
Hypertension
Yes	387 (77.4)	0.281	0.285	0.050	0.889	0.472
No	113 (22.6)
Alcohol
Yes	92 (18.4)	0.160	0.096	0.088	0.100	0.219
No	408 (81.60)
Smoking
Yes	181 (36.2)	0.018	0.032	0.103	0.726	0.464
No	319 (63.80
Diabetes
Yes	84 (16.8	0.137	0.192	0.132	0.319	0.663
No	416 (83.20
Warning leak
Yes	9 (1.8)	0.803	0.349	0.139	0.238	0.538
No	491 (98.2)
Multiplicity
Single aneurysm	410 (82)	0.151	0.090	0.090	0.547	0.663
Multiple aneurysm	90 (18)
Timing of surgery	254 (50.8)
Emergency	246 (49.2)	0.044	0.070	0.095	0.169	0.259
Elective	254 (50.8)

Table 3 Demographic, clinical, radiological, surgical characteristics, and functional outcome (Glasgow Coma Scale) of patients after microsurgical clipping at discharge and subsequent follow-up

Variable	No. of patients (%)	Follow-up
		At discharge (p-Value)	6 mo (p-Value)	1 y (p-Value)	5 y (p-Value)	10 y (p-Value)
Neck size
>4 mm	93 (18.6)	0.242	0.221	0.434	0.932	0.579
≤4 mm	407 (81.4)
Mean neck size	0.814 mm
Size of aneurysm
11–25 mm (large)	66 (13.39)	0.860	0.876	0.816	0.778	0.912
<11 mm (small)	427 (86.61)
Mean aneurysm size	7.46 mm
Intraoperative rupture
Yes	53 (10.6)	0.114	0.142	0.005	0.000	0.006
No	447 (89.4)
Hydrocephalus
Yes	98 (19.6)	0.537	0.660	0.526	0.128
No	402 (80.4)
Brain retraction
Yes	328 (65.6)	0.357	0.687	0.774	0.309	0.237
No	172 (34.4)
Lamina terminalis fenestration
Yes	142 (28.4)	0.676	0.514	0.573	0.850	0.457
No	358 (71.6)
Vasospasm
Yes	181 (36.2)	0.000	0.000	0.000	0.014	0.114
No	319 (63.8)
Covid pandemic
Yes	22 (4.4)	0.000	0.001	0.278	0.256	0.269
No	478 (95.6)

Table 4 Level of significance: comparison of variables in relation to Glasgow Outcome Scale at the time of discharge

Variable	Odds Ratio	Standard error	z	p > z	95% confidence interval
Female	0.502	0.166	–2.09	0.037	0.2625	0.9591
Age	2.155	0.906	1.82	0.068	0.9446	4.9144
Patient history: hypertension	0.606	0.281	–1.08	0.281	0.2441	1.5055
Patient history: alcohol	0.571	0.228	–1.41	0.16	0.2615	1.2470
Patient history: smoking	0.433	0.154	–2.36	0.018	0.2161	0.8688
Patient history: diabetes mellitus	0.594	0.208	–1.49	0.137	0.2988	1.1809
Multiplicity	1.681	0.608	1.44	0.151	0.8270	3.4157
Use of temporary clip	1.210	0.365	0.63	0.529	0.6694	2.1856
Hunt and Hess grade	3.237	0.995	3.82	0.000	1.7722	5.9121
Miller Fisher grade	2.061	0.814	1.83	0.067	0.9499	4.4704
Transcranial Doppler	1.340	0.534	0.73	0.463	0.6134	2.9264
Intraoperative rupture	1.970	0.844	1.58	0.114	0.8505	4.5611
Neck size	0.636	0.246	–1.17	0.242	0.2975	1.3586
Aneurysm size	1.007	0.038	0.18	0.86	0.9350	1.0839
Location of aneurysm	2.480	1.064	2.12	0.034	1.0699	5.7493
Use of brain retractor	0.761	0.226	–0.92	0.357	0.4256	1.3608
Ethnicity	0.610	0.226	–1.33	0.182	0.2951	1.2609
Hydrocephalus	1.218	0.389	0.62	0.537	0.6512	2.2790
COVID-19 Pandemic	0.077	0.047	–4.2	0.000	0.0232	0.2547
Lamina terminalis fenestration	1.142	0.364	0.42	0.676	0.6116	2.1339
Vasospasm	0.162	0.046	–6.38	0.000	0.0930	0.2838
Hospital: private/government	1.138	0.385	0.38	0.703	0.5860	2.2098
Warning leak	0.772	0.799	–0.25	0.803	0.1015	5.8728
Timing of surgery	1.814	0.536	2.02	0.044	1.0173	3.2362

Table 5 Level of significance: comparison of variables in relation to Glasgow Outcome Scale at 6 months of follow-up

Variable	Odds ratio	Standard error	z	p > z	95% confidence interval
Female	0.549	0.180	-1.83	0.067	0.2894	1.0431
Age	2.091	0.889	1.73	0.083	0.9085	4.8129
Patient history: hypertension	0.608	0.283	–1.07	0.285	0.2439	1.5145
Patient history: alcohol	0.507	0.207	–1.66	0.096	0.2276	1.1289
Patient history: smoking	0.457	0.167	–2.14	0.032	0.2233	0.9349
Patient history: diabetes mellitus	0.629	0.223	–1.3	0.192	0.3139	1.2620
Multiplicity	1.862	0.683	1.7	0.09	0.9077	3.8196
Use of temporary clip	1.256	0.383	0.75	0.455	0.6908	2.2829
Hunt and Hess grade	3.379	1.051	3.92	0.000	1.8367	6.2147
Miller Fisher grade	1.601	0.602	1.25	0.211	0.7661	3.3460
Transcranial Doppler	1.235	0.505	0.52	0.606	0.5541	2.7531
Intraoperative rupture	1.873	0.801	1.47	0.142	0.8098	4.3316
Neck size	0.621	0.242	–1.22	0.221	0.2890	1.3323
Aneurysm size	0.994	0.037	–0.16	0.876	0.9237	1.0700
Location of aneurysm	2.890	1.235	2.48	0.013	1.2501	6.6796
Use of brain retractor	0.888	0.262	–0.4	0.687	0.4975	1.5836
Ethnicity	0.553	0.209	–1.57	0.117	0.2633	1.1597
Hydrocephalus	1.152	0.372	0.44	0.66	0.6124	2.1677
COVID-19 pandemic	0.088	0.064	–3.36	0.001	0.0215	0.3636
Lamina terminalis fenestration	1.235	0.399	0.65	0.514	0.6551	2.3277
Vasospasm	0.152	0.043	–6.66	0.000	0.0874	0.2647
Hospital: private/government	1.130	0.379	0.36	0.717	0.5850	2.1815
Warning leak	0.375	0.393	–0.94	0.349	0.0483	2.9198
Timing of surgery	1.714	0.511	1.81	0.070	0.9561	3.0740

Table 6 Level of significance: comparison of variables in relation to Glasgow Outcome Scale at 1 year of follow-up

Variable	Odds ratio	Standard error	z	p > z	95% conf interval
Female	0.462	0.204	–1.75	0.08	0.1946	1.0976
Age	1.558	0.922	0.75	0.454	0.4884	4.9694
Patient history: hypertension	0.213	0.168	–1.96	0.05	0.0455	0.9971
Patient history: alcohol	0.401	0.215	–1.7	0.088	0.1403	1.1472
Patient history: smoking	0.457	0.220	–1.63	0.103	0.1783	1.1723
Patient history: diabetes mellitus	0.509	0.228	–1.51	0.132	0.2109	1.2264
Multiplicity	2.338	1.170	1.7	0.09	0.8766	6.2343
Use of temporary clip	1.473	0.570	1	0.317	0.6895	3.1461
Hunt and Hess grade	2.680	1.047	2.52	0.012	1.2456	5.7650
Miller Fisher grade	1.628	0.784	1.01	0.311	0.6338	4.1813
Transcranial Doppler	3.855	2.238	2.32	0.020	1.2356	12.0296
Intraoperative rupture	4.478	2.370	2.83	0.005	1.5865	12.6371
Neck size	0.667	0.346	–0.78	0.434	0.2412	1.8423
Aneurysm size	1.011	0.049	0.23	0.816	0.9203	1.1111
Location of aneurysm	2.152	1.197	1.38	0.168	0.7231	6.4022
Use of brain retractor	0.897	0.340	–0.29	0.774	0.4263	1.8857
Ethnicity	0.223	0.132	–2.53	0.011	0.0699	0.7143
Hydrocephalus	1.298	0.533	0.63	0.526	0.5802	2.9021
COVID-19 pandemic	0.208	0.301	–1.09	0.278	0.0122	3.5457
Lamina terminalis fenestration	1.276	0.553	0.56	0.573	0.5462	2.9835
Vasospasm	0.084	0.034	–6.14	0.000	0.0379	0.1846
Hospital: private/government	0.633	0.259	–1.12	0.265	0.2839	1.4130
Warning leak	0.122	0.174	–1.48	0.139	0.0076	1.9760
Timing of surgery	1.867	0.699	1.67	0.095	0.8970	3.8879

Table 7 Level of significance: comparison of variables in relation to Glasgow Outcome Scale at 5 years of follow-up

Variable	Odds ratio	Standard error	Z	p > z	95% confidence interval
Female	0.375	0.320	–1.15	0.25	0.071	1.996
Age	0.334	0.349	–1.05	0.293	0.043	2.585
Patient history: hypertension	1.170	1.321	0.14	0.889	0.128	10.686
Patient history: alcohol	0.224	0.204	–1.64	0.1	0.038	1.334
Patient history: smoking	0.717	0.680	–0.35	0.726	0.112	4.600
Patient history: diabetes mellitus	0.422	0.365	–1	0.319	0.077	2.302
Multiplicity	1.760	1.650	0.6	0.547	0.280	11.059
Use of temporary clip	1.983	1.326	1.02	0.306	0.535	7.353
Hunt and Hess grade	1.929	1.324	0.96	0.339	0.502	7.403
Millar Fisher grade	2.310	2.018	0.96	0.338	0.417	12.802
Transcranial Doppler	1.346	1.293	0.31	0.757	0.205	8.849
Intraoperative rupture	33.947	27.863	4.29	0	6.794	169.609
Neck size	0.920	0.899	–0.08	0.932	0.136	6.247
Aneurysm size	0.977	0.082	–0.28	0.778	0.828	1.152
Location of aneurysm	5.044	4.833	1.69	0.091	0.771	32.991
Use of brain retractor	2.049	1.445	1.02	0.309	0.514	8.166
Ethnicity	0.782	0.651	–0.3	0.767	0.153	3.994
Hydrocephalus	3.911	3.499	1.52	0.128	0.677	22.590
COVID-19 pandemic	1.000
Lamina terminalis fenestration	0.866	0.662	–0.19	0.85	0.194	3.874
Vasospasm	0.181	0.126	–2.46	0.014	0.047	0.707
Hospital: private/government	0.994	0.748	–0.01	0.993	0.227	4.346
Warning leak	1.000
Timing of surgery	2.507	1.673	1.38	0.169	0.678	9.272

Table 8 Level of significance: comparison of variables in relation to Glasgow Outcome Scale (GOS) at 10 years of follow-up

Variable	Odds ratio	Standard error	Z	p > z	95% confidence interval
Female	4.288	8.411	0.74	0.458	0.09	200.38
Age	0.639	1.278	–0.22	0.823	0.01	32.31
Patient history: hypertension	0.158	0.405	–0.72	0.472	0.00	24.14
Patient history: alcohol	18.320	43.385	1.23	0.219	0.18	1899.92
Patient history: smoking	0.251	0.474	–0.73	0.464	0.01	10.13
Patient history: diabetes mellitus	0.431	0.831	–0.44	0.663	0.01	18.84
Multiplicity	4.017	7.701	0.73	0.468	0.09	172.13
Use of temporary clip	12.705	18.942	1.7	0.088	0.68	236.08
Hunt and Hess grade	0.639	1.088	–0.26	0.792	0.02	18.03
Miller Fisher grade	6.132	11.926	0.93	0.351	0.14	277.44
Transcranial Doppler	1.000
Intraoperative rupture	149.280	269.783	2.77	0.006	4.32	5156.01
Neck size	2.540	4.267	0.55	0.579	0.09	68.34
Aneurysm size	0.982	0.163	–0.11	0.912	0.71	1.36
Location of aneurysm	13.233	39.722	0.86	0.39	0.04	4750.29
Use of brain retractor	11.508	23.799	1.18	0.237	0.20	662.63
Ethnicity	0.846	1.685	–0.08	0.933	0.02	41.99
Hydrocephalus	1.000
COVID-19 pandemic	1.000
Lamina terminalis fenestration	0.067	0.243	–0.74	0.457	0.00	83.73
Vasospasm	0.096	0.143	–1.58	0.114	0.01	1.75
Hospital: private/government	31.995	115.152	0.96	0.336	0.03	37032.26
Warning leak	1.000
Timing of surgery	5.982	9.480	1.13	0.259	0.27	133.60

Table 9 Glasgow Outcome Scale (GOS) score of patients following cerebral aneurysm clipping at discharge and subsequent follow-up

Follow-up	GOS score	No. of patients (%)
At discharge
	Favorable outcome	385 (77)
	Unfavorable outcome	115 (23)
6 mo
	Favorable outcome	376 (76.58)
	Unfavorable outcome	115 (23.42)
1 y
	Favorable outcome	379 (85.36)
	Unfavorable outcome	65 (14.64)
3 y
	Favorable outcome	388 (90.44)
	Unfavorable outcome	41 (9.56)
5 y
	Favorable outcome	380 (95.48)
	Unfavorable outcome	18 (4.52)
10 y
	Favorable outcome	366 (96.83)
	Unfavorable outcome	12 (3.17)

Discussion

The immediate and long-term outcomes of IA treatment, whether open or endovascular, are influenced by numerous factors, many of which have been previously studied. These include age, sex, diabetes mellitus, hypertension, smoking, alcohol abuse, H&H clinical grade, modified Fisher grade, aneurysm multiplicity, intracerebral hemorrhage, timing of surgery, surgical volume, aneurysm location, aneurysm size, neck size, IOR, vasospasm, and temporary occlusion of parent vessels.[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] However, the results of these studies have often been mixed and controversial. Additionally, some previously unstudied factors, such as hydrocephalus, LTF, brain retraction during surgery, ethnicity, type of hospital (private or government), and the COVID-19 pandemic, may also affect outcomes. This study aimed to examine all potential modifiable and unmodifiable factors that could alter immediate or long-term outcomes after microsurgical clipping of IAs.

Age has been considered a known risk factor for poor outcomes after aneurysm clipping.[6] [7] [11] [14] [17] [18] [24] [25] However, other studies found no difference in outcomes between younger and older patients.[9] [19] [20] [22] Our study supports the latter findings, showing no significant difference in outcome at discharge (p = 0.068) or subsequent follow-ups. The question of whether sex is an influencing factor remains debatable. Our study revealed poorer outcomes in females at discharge (p = 0.037), but no difference thereafter ([Fig. 2]). This contrasts with Rosenłrn et al's series of 1,076 cases, which observed poorer outcomes in females, potentially attributable to a higher incidence of vasospasm.[10] Conversely, Duijghuisen et al's study of 176 patients found no sex-based outcome differences after microsurgical clipping.[13] Similarly, Roganović and Pavlićević's series of 111 patients with ACAs found no difference between sexes.[19]

Fig. 2 Diagrams comparing the outcome (GOS) of male and female patients at discharge, and at the first (6 months) and last (10 years) follow-ups. GOS, Glasgow Outcome Scale.

In Nepal, two major ethnic groups, Aryan and Mongol, comprise 80% of the population. To our knowledge, no prior study has examined the impact of ethnicity on aneurysm clipping outcomes in these groups. Our study found no significant difference in outcomes at discharge (p = 0.182) or during follow-up. The senior surgeon (G.R.S.) has practiced neurovascular surgery in both government and private hospitals for 15 years, performing 60% of aneurysm clippings in government and 40% in private settings. We sought to determine whether the type of hospital influenced outcomes. Interestingly, we found no statistically significant difference in outcomes at discharge (p = 0.703), 6 months (p = 0.717), 1 year (p = 0.265), 5 years (p = 0.993), or 10 years (p = 0.336). To our knowledge, no comparative studies have examined this question in the existing literature.

Aneurysm location is a key determinant of outcome after open surgery. Numerous studies have demonstrated that patients with ACAs have better outcomes than those with posterior circulation aneurysms.[6] [9] Our study corroborates these findings, with patients harboring posterior circulation aneurysms exhibiting poorer outcomes at discharge (p = 0.034) and 6 months (p = 0.013). However, outcomes were similar between the two groups after 1 year and at subsequent follow-ups ([Fig. 3]).

Fig. 3 This bar diagram reveals that patients operated for posterior circulation aneurysms had inferior outcome at discharge and at the first (6 months) and last (10 years) follow-ups. GOS, Glasgow Outcome Scale.

Preoperative H&H clinical grade significantly impacts outcomes. Previous studies have consistently shown that patients with lower H&H grades experience better outcomes than those with higher H&H grades after subarachnoid hemorrhage.[6] [7] [11] [14] [15] [16] [20] Our results align with these findings, demonstrating better functional outcomes in patients with lower H&H grades at discharge (p < 0.001), 6 months (p < 0.001), and 1 year (p = 0.012), with no difference thereafter.

Modified Fisher grade, another potential prognostic factor, has been linked to poor outcomes in patients with intracerebral hemorrhage in several studies.[7] [16] [17] [25] However, our study found no significant difference in outcomes based on modified Fisher grade ([Fig. 4]).

Fig. 4 Bar diagrams representing the trend of GOS of patients in relation to MFG at discharge, first (6 months) and last (10 years) follow up. GOS, Glasgow Outcome Scale; MFG, modified Fisher grade.

While hypertension has been suggested as a factor influencing aneurysm clipping outcomes,[5] [14] [17] [25] our study found no significant impact of preexisting hypertension on patient outcomes.

The literature on the effect of smoking on postaneurysm surgery outcomes is limited and presents conflicting results. Rienas et al showed that although tobacco smoking is commonly a risk factor for vascular diseases and postoperative complications, it is not a risk factor for the postoperative outcomes that they analyzed during craniotomy for aSAH.[26] Addis et al mentioned about how smoking damages blood vessels, potentially impairing their ability to heal and increasing the risk of complications like vasospasm after an aneurysm ruptures.[27] Son et al reported worse outcomes in smokers,[18] while Slettebø et al found that although smokers presented with poorer clinical grades after SAH, smoking did not predict mortality or poor functional outcome.[28] In our study, smokers had worse outcomes than nonsmokers at discharge (p = 0.018) and 6 months (p = 0.032).

The impact of alcohol abuse on aneurysm clipping outcomes is understudied. Our study found no significant difference in outcomes between patients with and without a history of alcohol abuse at discharge (p = 0.160), 6 months (p = 0.096), 1 year (p = 0.088), 5 years (p = 0.100), and 10 years (p = 0.219).

While comorbidities like diabetes mellitus may influence functional outcomes after microsurgical clipping, the evidence is limited. Son et al, in a study of 50 patients over 65 undergoing microsurgical clipping, identified diabetes mellitus as an independent prognostic factor associated with poorer outcomes.[18] However, their study found no significant difference in outcomes between diabetic and nondiabetic patients.

The effect of warning leaks on patient outcomes after microsurgical clipping remains unclear due to limited research. Ritz and Reif, in a study of 214 patients with subarachnoid hemorrhage following aneurysm clipping, concluded that long-term outcomes in the warning leak group were not negatively affected by angiographically proven vasospasm.[29] Similarly, our study did not detect any impact of warning leaks on patient outcomes.

Aneurysm multiplicity did not influence patient outcomes after surgical intervention at discharge (p = 0.15), 6 months (p = 0.090), 1 year (p = 0.090), 5 years (p = 0.169), and 10 years (p = 0.663) in our series, and there is no relevant literature addressing this issue.

While many studies have found no significant difference in the GOS score between early and late surgical groups,[11] [17] [20] [23] our study observed better outcomes in the early surgery (<72 hours) group compared with the late surgery (>72 hours) group at discharge (p = 0.044), but, surprisingly, no difference in outcomes thereafter. Early aneurysm clipping may prevent rebleeding and reduce vasospasm, potentially leading to improved patient outcomes.

Aneurysm and neck size are controversial risk factors for outcomes after clipping. While our study found no effect of aneurysm or neck size on GOS at up to 10 years of follow-up, some studies have reported poorer prognoses for patients with large or giant aneurysms and wide necks.[17] [18] [24] Conversely, other studies have found no difference in outcome based on aneurysm size or neck width.[9] [19] [20]

Vasospasm is a strong risk factor for poor prognosis after surgical clipping,[9] [10] [14] [16] often leading to cerebral infarction and delayed ischemic deficits. Our study confirmed this, with poorer outcomes observed in patients with cerebral vasospasm at discharge (p < 0.001), 6 months (p < 0.001), 1 year (p < 0.001), and 5 years (p = 0.014). However, there was no difference in outcome at 10 years ([Fig. 5]).

Fig. 5 The doughnut chart showing clinical outcome of these two groups of patients (hydrocephalus vs. nonhydrocephalus) at discharge, and at the first (6 months) and last (10 years) follow-ups. GOS, Glasgow Outcome Scale.

Retractorless aneurysm surgery has been associated with adequate aneurysm visualization and excellent surgical outcomes.[30] However, no comparative studies have examined outcomes with and without brain retractors in patients undergoing IA clipping. Our study, surprisingly, found no difference in outcome based on retractor use during clipping.

Cengiz et al conducted a study of 72 patients with aSAH undergoing clipping and concluded that wide LTF may be beneficial in the surgical treatment of aSAH, finding better outcomes in the LTF group than in the non-LTF group.[31] Two other studies also suggested that LTF reduces poor outcomes by minimizing the incidence of shunt-dependent hydrocephalus and internal blood clotting.[32] [33] However, this study found no effect of LTF on patient outcomes after aneurysm clipping.

Hydrocephalus has been considered a negative prognostic factor in aneurysm surgery.[14] However, our study found no difference in outcome between patients with and without hydrocephalus. Addis et al discussed ICP monitoring and management in the context of aSAH where hydrocephalus can elevate intracranial pressure, which can further compromise cerebral blood flow and exacerbate brain injury leading to detrimental outcomes.[27]

IOR has been identified as a determinant of worse prognosis after surgical clipping.[34] [35] [36] [37] In our series, IOR did not affect patient outcomes at discharge (p = 0.114) or at 6 months (p = 0.142). However, the non-IOR group had significantly better outcomes at 1 year (p = 0.005), 5 years (p < 0.001), and 10 years (p = 0.006).

The COVID-19 pandemic caused a significant global health crisis. While initially considered a respiratory disease, SARS-CoV-2 has the potential to disseminate throughout the body, causing multi-organ failures, including central nervous system manifestations such as stroke, meningoencephalitis, and dural sinus thrombosis.[38] [39] This study aimed to determine the impact of the COVID-19 pandemic on outcomes in patients undergoing microsurgical clipping of IAs. Comparing patients operated on during the pandemic and nonpandemic periods, we found that patients undergoing clipping during the pandemic had surprisingly poorer prognoses at discharge (p < 0.001) and 6 months (p = 0.001). However, there was no difference in outcome at 1 year (p = 0.278), 5 years (p = 0.25), and 10 years (p = 0.269). This poorer initial prognosis might be attributed to underlying comorbidities such as immunosuppression, thrombocytopenia, encephalitis, or other systemic involvement by SARS-CoV-2. However, no comparative studies have been conducted on these two groups of IA surgery patients.

Finally, this study revealed a gradual improvement in patient outcomes following aneurysm clipping on subsequent follow-up, even when immediate results were not promising. Gupta et al published a case series of 494 patients with aneurysm clipping, and their long-term results were similar to the results of this study.[40]

Limitations

This retrospective study, while encompassing multicenter data from a single surgeon, still has limitations. Using preexisting data may introduce bias and limit causal inferences. While the multicenter aspect improves generalizability compared with a single-center study, variations in patient populations, resources, and data collection practices across the different centers could still influence outcomes. Despite the surgeon being constant, differences in supporting staff and perioperative protocols across centers could introduce variability. Furthermore, unmeasured confounding variables remain a possibility. The specific follow-up duration is not detailed, limiting the assessment of long-term effects. Finally, data extracted from medical records may contain errors.

Conclusion

Postoperative vasospasm, IOR, and the COVID-19 pandemic were the most important predictors of worse outcomes in patients who underwent microsurgical clipping for ruptured IAs. Sex, aneurysm location, H&H clinical grade, smoking, hypertension, and timing of surgery were other factors influencing prognosis. While age, type of hospital, modified Fisher grade, alcohol abuse, diabetes mellitus, aneurysm multiplicity, ethnicity, aneurysm size, aneurysm neck size, hydrocephalus, and use of brain retractors did not significantly impact outcomes in this study, further research is needed to fully elucidate their potential roles. This study demonstrated an increasing trend of functional outcome improvement on subsequent follow-up, even when the initial outcome was not encouraging, suggesting the importance of long-term monitoring and rehabilitation. Early aneurysm clipping may prevent rebleeding and reduce vasospasm, potentially leading to improved patient outcomes; however, further investigation is warranted to confirm these potential benefits and refine optimal timing strategies for intervention.

Conflict of interest

None declared.

Acknowledgments

We would like to express our sincere gratitude to Kriti Basnet and Prashant Bhattarai from the Department of Neurosciences for their invaluable assistance in the preparation of this manuscript.

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Publication History

Article published online:
20 February 2025