Preoperative and postoperative predictors of long-term outcome after endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage

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1 CLINICAL ARTICLE J Neurosurg 126: , 2017 Preoperative and postoperative predictors of long-term outcome after endovascular treatment of poor-grade aneurysmal subarachnoid hemorrhage *Bing Zhao, MD, 1,2 Hua Yang, MD, 3 Kuang Zheng, MD, 1 Zequn Li, MD, 1 Ye Xiong, MD, 1 Xianxi Tan, MD, 1 Ming Zhong, MD, 1 and the AMPAS Study Group 1 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; 2 Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota; and 3 Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China OBJECTIVE An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (asah) have received endovascular treatment. Endovascular treatment of poor-grade asah, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade asah. METHODS A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade asah. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mrs) score at 12 months, and poor outcome was defined as an mrs score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model s discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration. RESULTS At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mrs score of 4, 6 (4.4%) had an mrs score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI , p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI , p < 0.001). Both models had good calibration (p = and p = 0.653, respectively). CONCLUSIONS Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade asah. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade asah with ruptured wide-neck aneurysms. CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I. KEY WORDS intracranial aneurysm; subarachnoid hemorrhage; poor grade; endovascular treatment; prognosis; risk factors; vascular disorders ABBREVIATIONS ACoA = anterior communicating artery; AMPAS = A Multicenter Poor-grade Aneurysm Study; asah = aneurysmal subarachnoid hemorrhage; AUC = area under receiver operating characteristic curve; CI = confidence interval; GCS = Glasgow Coma Scale; mrs = modified Rankin Scale; OR = odds ratio; WFNS = World Federation of Neurosurgical Societies. SUBMITTED November 8, ACCEPTED April 14, INCLUDE WHEN CITING Published online July 1, 2016; DOI: / JNS * Drs. Zhao and Yang contributed equally to this work J Neurosurg Volume 126 June 2017 AANS, 2017

2 Endovascular treatment of poor-grade subarachnoid hemorrhage Aneurysmal subarachnoid hemorrhage (asah) is a devastating condition that is associated with high rates of morbidity and mortality. Patients with poor-grade asah have high risks of aneurysm rebleeding and cerebral vasospasm. Aggressive surgery has been proposed to improve outcomes in selected patients. 1,4,7,8,22 In recent decades, endovascular coiling has provided a viable alternative to surgical treatment for asah. Case series showed that early endovascular treatment of poorgrade asah is a feasible and reasonable option, 2,3,23 and an increasing number of patients with poor-grade asah have received endovascular treatment. 5,15,19,20 Predicting outcome after endovascular treatment of poor-grade asah may be helpful in determining which patients benefit from endovascular treatment and for informing the family about prognosis. A few studies have reported prognostic models focused on surgical treatment of poor-grade asah. 9,14,28 However, endovascular treatment for poor-grade asah is based on single-center retrospective studies. Predictors of outcome after endovascular treatment are not well defined. 15 Using data from A Multicenter Poor-grade Aneurysm Study (AMPAS) we developed preoperative and postoperative prognostic models to predict poor outcome at 12 months. Methods Study Design and Patient Population The AMPAS study was a prospective, multicenter, observational registry of consecutive patients who presented with poor-grade asah. (AMPAS study investigators are listed in an Appendix.) The study protocol was approved by the Chinese Ethics Committee of Registering Clinical Trials and was published elsewhere. 26 All informed consent was obtained from the patient s legal representative. Poor-grade asah was defined as a World Federation of Neurosurgical Societies (WFNS) grade of IV or V. From October 2010 to March 2012, 366 patients were treated at tertiary referral hospitals (more than 150 asah cases per year) with expertise in aneurysm coiling and clipping, and 143 patients received endovascular treatment. In this report, 136 patients (95.1%) who presented with poor-grade asah at the time of treatment were included and 7 were excluded because they experienced neurological improvement from an initial poor grade (WFNS grade of IV or V) to a good grade (WFNS grade of I III) after resuscitation. CLASSIFICATION OF EVIDENCE Type of Question Prognostic Study Design Retrospective Cohort Trial Evidence Class I Zhao and colleagues present the results of a retrospective cohort study investigating potential predictors of poor outcome in patients presenting with poor-grade aneurysmal subarachnoid hemorrhage (asah) receiving endovascular intervention. This study provides Class I evidence for the association of age, World Federation of Neurosurgical Societies (WFNS) Grade V, modified Fisher grade, and aneurysm neck size (the authors preoperative model) and age, WFNS Grade V, modified Fisher grade, aneurysm neck size, and pneumonia (the authors postoperative model) with poor outcome (modified Rankin Scale score > 3) in patients with poor-grade asah undergoing endovascular therapy, but the false-positive rate of both models (approximately 25%) is too high to guide decisions regarding withholding or withdrawal of care in most circumstances. The authors suggest that endovascular treatment should be carefully considered in patients with poorgrade ruptured wide-neck aneurysms and that aggressively treating postoperative pneumonia may improve outcomes. These are therapeutic questions for which the authors have no comparison group. Despite their plausibility, these assertions must be considered hypotheses (Class IV evidence) and are insufficient to support a treatment recommendation. It is important to note that different questions within the same study can carry different weights of evidence. Clinical Treatment Protocol All patients were initially managed in the emergency room. Treatment protocol included aggressive resuscitation, early CT angiography or cerebral angiography, multidisciplinary team consultation, early aneurysm treatment, and intensive critical care treatment The multidisciplinary team consisted of vascular neurosurgeons, neurointerventionists, and anesthetists. Endovascular treatment was considered in patients with ruptured aneurysms whose characteristics were suitable for coiling or could not be successfully treated with clipping, or in those with posterior circulation aneurysms. Stent-assisted coiling or balloon-assisted coiling was considered in patients with wide-neck aneurysms (neck size 4 mm or dome-neck ratio 2) or dissecting aneurysms. Aspirin-clopidogrel therapy was prescribed according to individual institutional standards. External ventricular drainage was considered in patients with acute hydrocephalus or severe intraventricular hemorrhage before or after treatment. All patients were transferred to the intensive care unit, and they received standard management for vasospasm with nimodipine, hypervolemia, and induced hypertension. Data Collection and Definitions We prospectively collected the following data: patient age, sex, medical history, Glasgow Coma Scale (GCS) score and WFNS grade, Fisher grade and modified Fisher grade, intraventricular hemorrhage, radiographic vasospasm, aneurysm characteristics, timing of treatment, procedural record and final angiographic results, postoperative external ventricular drain placement, and major complications during hospitalization. Imaging findings were defined as the last radiological examination images before treatment. The time of treatment was defined as the interval between the time of the onset of the poor clinical status and the time of aneurysm treatment. Immediate angiographic occlusion was assessed using Raymond grade determined by the neurointerventionist at each center, and complete occlusion was defined as a Raymond grade of I. Outcome Measures Clinical outcome at 12 months was assessed by inde- J Neurosurg Volume 126 June

3 B. Zhao et al. pendent neurosurgeons using the modified Rankin Scale (mrs). In view of the high rates of morbidity and mortality in patients with poor-grade asah, poor outcome was defined as an mrs score of 4 or 5, or death (6). Angiographic follow-up at 6 or 12 months was recommended but not required at each center. Statistical Analysis Statistical analysis was performed using SPSS (version 22.0., IBM). Differences in initial angiographic results, postoperative complications, and clinical outcomes were compared between patients with a WFNS grade of IV and those with a WFNS grade of V using a chi-square or Fisher s exact test. Associations between clinical variables and poor outcome were assessed using univariate logistic regression analysis. Any variables with missing values 5% were not included in the analysis. All variables with a p value 0.05 in univariate analysis were entered into the multivariate logistic regression analysis. A preoperative prognostic model (including baseline variables) and a postoperative model (baseline variables plus postoperative compilations) were developed to identify independent predictors of a poor outcome in the multivariate regression models using the backward logistic regression method. The area under receiver operating characteristic curve (AUC) was used to test the model s prediction ability. An AUC of was regarded as good discrimination, and an AUC of was regarded as excellent discrimination. The calibration of the prognostic model was assessed by a Hosmer-Lemeshow goodness-of-fit test, and a p value > 0.30 was regarded as good calibration. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A p value < 0.05 was considered statistically significant. Results Patient Characteristics Baseline characteristics of the 136 patients are presented in Table 1. The median time of treatment was 24 hours after poor-grade asah (range 0 35 days). One hundred one patients (74.3%) were treated within 72 hours. Thirty-five patients (25.7%) were treated after 72 hours: 22 (16.2%) were treated between after 72 hours and 7 days, 5 (3.7%) treated between 8 and 10 days, 3 (2.2%) treated between 11 and 14 days, 2 (1.5%) treated between 15 and 21 days, and 3 (2.2%) treated after 21 days. Of the 101 patients, 69 (68.3%) received treatment within 24 hours. Immediate Angiographic Results Immediate angiographic results are presented in Table 2. Initial complete occlusion was observed in 73 patients (86.9%) with a WFNS grade of IV and in 45 (86.5%) with a WFNS grade of V, which was not a statistically significant difference. Medical Postoperative Complications Major complications are presented in Table 2. There were significant differences in rates of cerebral infarction (p = 0.023) and pneumonia (p = 0.005) between patients with a WFNS grade of IV and those with a WFNS grade of V. There were trends toward increased risks of symptomatic vasospasm (p = 0.066) and hydrocephalus (p = 0.095) in patients with a WFNS grade of V. Long-Term Clinical Outcomes Outcomes at 12 months are presented in Table 2. Nine patients (6.6%) had an mrs score of 4, 6 (4.4%) had an mrs score of 5, and 49 (36.0%) had died. Fifty-nine patients (43.4%) had an mrs score of 0 or 1, and 64 (47.0%) had a poor outcome (mrs score 4 6). The outcomes in patients with a WFNS grade of V were worse than those in patients with a WFNS grade of IV (p < 0.001). Univariate Analyses for Predictors of a Poor Outcome Results of the univariate analysis for poor outcome are presented in Table 3. Older age (p = 0.001), female sex (p = 0.044), lower GCS score (p < 0.001), a WFNS grade of V (p < 0.001), higher Fisher grade (p < 0.001) and modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery (ACoA) aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate Analyses for Predictors of a Poor Outcome Multivariate regression models for prediction of poor outcome at 12 months are presented in Table 4. Older age (p = 0.006), a WFNS grade of V (p < 0.001), higher modified Fisher grade (p < 0.001), wider neck aneurysm (p = 0.028), and presence of pneumonia (p = 0.032) were independent predictors of poor outcome. The preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size showed excellent discrimination with an AUC of 0.86 (95% CI , p < 0.001). The postoperative prognostic model (AUC = 0.87, 95% CI , p < 0.001) had almost the same discriminatory performance as the preoperative model (Fig. 1). Preoperative and postoperative prognostic models had good calibration (p = and p = 0.653, respectively). Discussion This is a prospective, multicenter observational study of consecutive patients who received endovascular treatment. The data set is representative of the current endovascular practice in high-volume centers. Most patients underwent treatment within 72 hours of poor-grade asah, especially within 24 hours. The preoperative prognostic model including older age, WFNS grade of V, higher modified Fisher grade, and ruptured wider neck aneurysm, or the postoperative model including these factors as well as postoperative pneumonia, showed excellent discrimination. Both of the modes had good calibration. Early treatment or ultra-early treatment for poor-grade asah has been increasingly advocated but remains contro J Neurosurg Volume 126 June 2017

4 Endovascular treatment of poor-grade subarachnoid hemorrhage TABLE 1. Baseline characteristics* Characteristics All Patients (n = 136) WFNS Grade IV (n = 84) WFNS Grade V (n = 52) Mean age ± SD (yrs) 54.6 ± ± ± 12.9 Women 64 (47.1) 39 (46.4) 25 (48.1) Current smoking 49 (36.0) 30 (35.7) 19 (36.5) Hypertension 53 (39.0) 35 (41.7) 18 (34.6) Diabetes mellitus 10 (7.4) 8 (9.5) 2 (3.8) Mean preop GCS score ± SD 7.5 ± ± ± 1.0 Radiological findings Intraventricular hemorrhage 54 (39.7) 30 (35.7) 24 (46.2) Mean Fisher grade ± SD 3.1 ± ± ± 0.8 Grade I II 33 (24.3) 27 (32.1) 6 (11.5) Grade III IV 103 (75.7) 57 (67.9) 46 (88.5) Modified Fisher grade ± SD 2.5 ± ± ± 1.0 Grade I II 59 (43.4) 44 (52.4) 15 (28.9) Grade III IV 77 (56.6) 40 (47.6) 37 (71.1) Angiographic vasospasm 29 (21.3) 18 (21.4) 11 (21.2) Aneurysm characteristics Multiple aneurysms 22 (16.2) 14 (16.7) 8 (15.4) Ruptured aneurysm location MCA 12 (8.8) 8 (9.5) 4 (7.7) ACA 4 (2.9) 3 (3.6) 1 (1.9) ACoA 45 (33.1) 28 (33.3) 17 (32.7) ICA termination 4 (2.9) 3 (3.6) 1 (1.9) OphA 5 (3.7) 2 (2.4) 3 (5.8) AChA 3 (2.2) 3 (3.6) 0 PCoA 35 (25.7) 25 (29.8) 10 (19.2) Posterior circulation artery 28 (20.6) 12 (14.3) 16 (30.8) Aneurysm size in mm ± SD 5.7 ± ± ± 3.3 Mean aneurysm neck size in mm ± SD 2.9 ± ± ± 1.1 Mean dome-to-neck ratio ± SD 2.0 ± ± ± 1.0 Aneurysm morphology Saccular aneurysm 127 (93.4) 82 (97.6) 45 (86.5) Fusiform aneurysm 6 (4.4) 1 (1.2) 5 (9.6) Dissection aneurysm 3 (2.2) 1 (1.2) 2 (3.8) Treatment procedure External ventricular drainage 37 (27.2) 18 (21.4) 19 (36.5) Timing of treatment (hrs) (74.3) 59 (70.2) 42 (80.8) >72 35 (25.7) 25 (29.8) 10 (19.2) Stent-assisted coiling 24 (17.6) 15 (17.9) 9 (17.3) ACA = anterior cerebral artery; AChA = Anterior choroidal artery; ICA = internal carotid artery; MCA = middle cerebral artery; OphA = ophthalmic artery; PCoA = posterior communicating artery. * All data given as value (%) unless otherwise indicated. versial. 13,16,17,24,25,27 Ultra-early surgery has not been widely used for the treatment of poor-grade asah, probably because of difficulties in addressing brain swelling from severe hemorrhage, difficult dissection, and periprocedural complications. 16,28 However, we found that most patients underwent ultra-early endovascular treatment in our study. This finding may suggest that the advent of endovascular therapy may allow ultra-early treatment for poor-grade asah. The possible reason is that endovascular treatment has fewer technical limitations related to brain swelling and these limitations do not affect the technical aspects of the procedure. 10 Endovascular treatment can also be performed in continuity with the initial angiography and requires less time for treatment. The outcome is in agree- J Neurosurg Volume 126 June

5 B. Zhao et al. TABLE 2. Immediate angiographic results, complications, and long-term outcomes* Variable All Patients (n = 136) WFNS Grade IV (n = 84) WFNS Grade V (n = 52) p Value Immediate aneurysm occlusion Complete occlusion (%) 118 (86.8) 73 (86.9) 45 (86.5) Incomplete occlusion (%) Residual neck 10 (7.4) 7 (8.3) 3 (5.8) Dome filling 4 (2.9) 3 (3.6) 1 (1.9) Parent artery occluded 4 (2.9) 1 (1.2) 3 (5.8) Major postop complications (%) Cerebral infarction 15 (11.0) 5 (6.0) 10 (19.2) Symptomatic vasospasm 15 (11.0) 6 (7.1) 9 (17.3) Aneurysm rebleeding 6 (4.4) 3 (3.6) 3 (5.8) Hydrocephalus 20 (14.7) 9 (10.7) 11 (21.2) Pneumonia 32 (23.5) 13 (15.5) 19 (36.5) Renal failure 2 (1.5) 1 (1.2) 1 (1.9) mrs scores at 12 mos (%) < (43.4) 49 (58.3) 10 (19.2) 2 10 (7.4) 6 (7.1) 4 (7.7) 3 3 (2.2) 2 (2.4) 1 (1.9) (11.0) 7 (8.4) 8 (15.4) 6 49 (36.0) 20 (23.8) 29 (55.8) * All data given as value (%) unless otherwise indicated. Boldface type indicates statistical significance. ment with current studies showing that endovascular treatment results with a good outcome in 37.1% 56.9% of patients with poor-grade asah. 15,19,20 Major improvements in endovascular technology and neurointensive critical care may have contributed to improve outcomes. In addition, the multidisciplinary consensus may allow for improved patient selection, providing a high rate of complete occlusion of the aneurysm and good outcome. We found that older age, a WFNS grade of V, higher modified Fisher grade, wider neck aneurysm, and presence of postoperative pneumonia were independent predictors of poor outcome. Patient age, WFNS grade, and thick cisternal and ventricular blood after asah have been wellknown risk factors for outcome. 5,11,14,15,19 21 Patients with wider neck aneurysms were more likely to have a poor outcome. The underlying mechanism of this association is unclear but might be explained by lower rates of complete occlusion of wide-neck aneurysms. 12 The incomplete occlusion of aneurysms increases the risk of postoperative rebleeding. 6,18 Our results also showed that there was a trend toward a worse outcome in patients with incompletely occluded aneurysms, probably due to rebleeding. Although neurovascular stents are increasingly used safely in the treatment of unruptured wide-neck aneurysms, 12 the safety of endovascular coiling for ruptured wide-neck aneurysms requires further study. Therefore, the endovascular treatment of these aneurysms is challenging. These results may suggest that poor-grade wide-neck aneurysms may be considered for surgical clipping, which remains an important treatment modality for aneurysms in the endovascular era. These findings may also indicate that the development and application of new endovascular technology is needed to improve the complete occlusion rate of these aneurysms. In addition, preventing and aggressively treating postoperative pneumonia may help improve outcomes in patients with poor-grade asah. One strength of our study lies in the fact that these pre- FIG. 1. AUCs of the predictive value of outcome according to prognostic models. Figure is available in color online only J Neurosurg Volume 126 June 2017

6 Endovascular treatment of poor-grade subarachnoid hemorrhage TABLE 3. Univariate logistic analysis for predictors of poor outcome* Characteristics Good Outcome (n = 72) Poor Outcome (n = 64) OR (95% CI) p Value Mean age ± SD (yrs) 51.2 ± ± ( ) Female sex 28 (38.9) 36 (56.3) 2.0 ( ) Current smoking 30 (41.7) 19 (29.7) 0.6 ( ) Hypertension 23 (31.9) 30 (46.9) 1.4 ( ) Diabetes mellitus 3 (4.2) 7 (10.9) 1.5 ( ) Mean preop GCS score ± SD 8.3 ± ± ( ) <0.001 Preop WFNS Grade V 15 (20.8) 37 (57.8) 5.2 ( ) <0.001 Mean Fisher grade ± SD 2.8 ± ± ( ) <0.001 Mean modified Fisher grade ± SD 2.1 ± ± ( ) <0.001 Intraventricular hemorrhage 25 (34.7) 29 (45.3) 1.6 ( ) Angiographic vasospasm 16 (22.2) 13 (20.3) 0.9 ( ) Multiple aneurysms 10 (13.9) 12 (18.8) 1.4 ( ) MCA aneurysm 7 (9.7) 5 (7.8) 0.8 ( ) ACA aneurysm 2 (2.8) 2 (3.1) 1.1 ( ) ACoA aneurysm 19 (26.4) 26 (40.6) 1.9 ( ) ICA bifurcation aneurysm 3 (4.2) 1 (1.6) 0.4 (0 3.6) OphA aneurysm 1 (1.4) 4 (6.3) 4.7 ( ) AChA aneurysm 2 (2.8) 1 (1.6) 0.6 (0 6.3) PCoA aneurysm 20 (27.8) 15 (23.4) 0.8 ( ) Posterior circulation aneurysm 18 (25.0) 10 (15.6) 0.6 ( ) Mean aneurysm size ± SD 5.5 ± ± ( ) Mean aneurysm neck size ± SD 2.7 ± ± ( ) Mean dome-to-neck ratio ± SD 2.1 ± ± ( ) Treatment w/in 72 hrs 55 (76.4) 46 (71.9) 0.8 ( ) Stent-assisted coiling 11 (15.3) 13 (20.3) 1.4 ( ) Incomplete occlusion 4 (5.6) 10 (15.6) 3.2 ( ) External ventricular drainage 17 (23.6) 20 (31.3) 1.5 ( ) Intraoperative rupture 2 (2.8) 2 (3.1) 1.1 ( ) Cerebral infarction 4 (5.6) 11 (17.2) 3.5 ( ) Symptomatic vasospasm 4 (5.6) 11 (17.2) 3.5 ( ) Aneurysm rebleeding 1 (1.4) 5 (7.8) 6.0 ( ) Hydrocephalus 8 (11.1) 12 (18.8) 1.8 ( ) Pneumonia 10 (13.9) 22 (34.4) 3.2 ( ) Renal failure 1 (1.4) 1 (1.6) 1.1 ( ) * All data given as value (%) unless otherwise indicated. Boldface type indicates statistical significance. dictors were derived from a large number of patients with poor-grade asah in a prospective multicenter registry. Standard neurological scales, outcome assessment scores, and risk factors were systematically collected from all sites. We found limited added value of postoperative complications for the prediction of poor outcome when compared with the preoperative model that included older age, a WFNS grade of V, higher mrs score, and wider neck aneurysms. It does not mean that postoperative complications are not important; instead, due to the lack of a more effective treatment of cerebral infarction, symptomatic vasospasm may cause the limited value of our prediction. In addition, our recent study determined the predictors of outcome after surgical clipping within 72 hours. 25 The predictors of outcome in patients after surgery within 72 hours were almost the same as those in all patients treated with surgical clipping. 28 These predictors of outcome after coiling or clipping might apply to all patients treated at different time intervals. To the best of our knowledge, this is the first study focused on predictors of poor outcome after endovascular treatment of poor-grade SAH using a multicenter prospective study. However, our study has some limitations. First, treatment decisions were evaluated by a multidisciplinary team, and selected patients treated with endovascular treatment may result in a better outcome. Second, available information is insufficient to adequately compare outcome between early and delayed treatments because most patients were treated within 72 hours of poor-grade asah. The optimal timing of endovascular treatment is still uncertain and requires further J Neurosurg Volume 126 June

7 B. Zhao et al. TABLE 4. Predictors of poor outcome in multivariate regression models Predictors Preop Model p OR (95% CI) Value Postop Model p OR (95% CI) Value Age 1.1 ( ) ( ) WFNS Grade V 8.6 ( ) < ( ) <0.001 Modified Fisher grade 2.3 ( ) < ( ) <0.001 Aneurysm neck size 1.7 ( ) ( ) Postop pneumonia 3.6 ( ) study. Third, aneurysm neck size was independently associated with poor outcome. Unfortunately, we could not find an optimal cutoff value of the size of the aneurysm neck, nor could we find convincing results regarding the alternative repair strategies using the data on endovascular treatment of poor-grade asah. In addition, long-term imaging follow-up was not required, and these imaging results may also affect outcome. Nevertheless, the prognostic model is useful for designing randomized controlled trials and for stratification and covariate adjustment. These predictors may also guide clinicians and families in their assessment of the prognosis before endovascular treatment of poor-grade asah. Conclusions Our results showed older age, WFNS grade of V, higher modified Fisher grade, wider neck aneurysms, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade asah. The preoperative model had almost the same discrimination as the postoperative model. Further improvement of endovascular treatment of ruptured wide-neck aneurysms may help improve outcome after poor-grade asah. However, endovascular coiling should be carefully considered in patients with poor-grade asah and wideneck aneurysms, and pneumonia should be aggressively managed to improve patient outcome. Appendix AMPAS Study Investigators Hongqi Zhang, MD, Xuan Wu Hospital, Capital Medical University; Chuansheng Liang, MD, the First Hospital of China Medical University; Huaizhang Shi, MD, the First Affiliated Hospital of Harbin Medical University; Jing Xu, MD, the Second Affiliated Hospital, School of Medicine, Zhejiang University; Li Pan, MD, Wuhan General Hospital of Guangzhou Command; Xin Zhang, MD, Nanjing General Hospital of Nanjing Command; Gang Zhu, MD, West South Hospital, the Third Military Medical University; Jianping Deng, MD, Tang Du Hospital, the Fourth Military Medical University; Zhigang Wang, MD, the Second Affiliated Hospital, School of Medicine, Shandong University. Acknowledgments This work was supported by the Chinese Ministry of Health (grant WKJ ), the Ministry of Science and Technology of China (grant 2011BAI08B06), and Wenzhou Bureau of Science and Technology (grant Y ). References 1. 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8 Endovascular treatment of poor-grade subarachnoid hemorrhage ñuela F: Contribution of endovascular therapy to the management of poor-grade aneurysmal subarachnoid hemorrhage: Clinical and angiographic outcomes. J Neurosurg 105: , 2006 [Erratum in J Neurosurg 106:204, 2007] 20. Taylor CJ, Robertson F, Brealey D, O Shea F, Stephen T, Brew S, et al: Outcome in poor grade subarachnoid hemorrhage patients treated with acute endovascular coiling of aneurysms and aggressive intensive care. Neurocrit Care 14: , Uozumi Y, Sakowitz O, Orakcioglu B, Santos E, Kentar M, Haux D, et al: Decompressive craniectomy in patients with aneurysmal subarachnoid hemorrhage: a single-center matched-pair analysis. Cerebrovasc Dis 37: , Versari PP, Talamonti G, D Aliberti G, Villa F, Solaini C, Collice M: Surgical treatment of poor-grade aneurysm patients. J Neurosurg Sci 42 (1 Suppl 1):43 46, Weir RU, Marcellus ML, Do HM, Steinberg GK, Marks MP: Aneurysmal subarachnoid hemorrhage in patients with Hunt and Hess grade 4 or 5: treatment using the Guglielmi detachable coil system. AJNR Am J Neuroradiol 24: , Wong GK, Boet R, Ng SC, Chan M, Gin T, Zee B, et al: Ultra-early (within 24 hours) aneurysm treatment after subarachnoid hemorrhage. World Neurosurg 77: , Zhao B, Cao Y, Tan X, Zhao Y, Wu J, Zhong M, et al: Complications and outcomes after early surgical treatment for poor-grade ruptured intracranial aneurysms: A multicenter retrospective cohort. Int J Surg 23 (Pt A):57 61, Zhao B, Tan X, Yang H, Zheng K, Li Z, Xiong Y, et al: A multicenter prospective study of poor-grade aneurysmal subarachnoid hemorrhage (AMPAS): observational registry study. BMC Neurol 14:86, Zhao B, Tan X, Zhao Y, Cao Y, Wu J, Zhong M, et al: Variation in patient characteristics and outcomes between early and delayed surgery in poor-grade aneurysmal subarachnoid hemorrhage. Neurosurgery 78: , Zhao B, Zhao Y, Tan X, Cao Y, Wu J, Zhong M, et al: Factors and outcomes associated with ultra-early surgery for poorgrade aneurysmal subarachnoid haemorrhage: a multicentre retrospective analysis. BMJ Open 5:e007410, 2015 Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author Contributions Conception and design: Zhong, Zhao, Yang. Acquisition of data: Zhao, Yang, Zheng, Li, Xiong, Tan. Analysis and interpretation of data: all authors. Drafting the article: Zhao. Critically revising the article: Zhong, Zhao, Yang. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Zhong. Statistical analysis: Zhao, Yang. Administrative/technical/material support: Zhao. Study supervision: Zhong. Correspondence Ming Zhong, Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbai Xiang, Wenzhou , China. zhongming158@sohu.com. J Neurosurg Volume 126 June