Increased Body Mass Index Associated With Reduced Risk of Delayed Cerebral Ischemia and Subsequent Infarction After Aneurysmal Subarachnoid Hemorrhage

Increased Body Mass Index Associated With Reduced Risk of Delayed Cerebral Ischemia and... Abstract BACKGROUND Increased body mass index (BMI) may be protective against cerebral ischemia in certain clinical contexts. OBJECTIVE To investigate whether increased BMI was associated with delayed cerebral ischemia (DCI) and subsequent infarction after aneurysmal subarachnoid hemorrhage (aSAH). METHODS We retrospectively reviewed the clinical course of patients presenting to our institution for management of aSAH. Patient were segregated according to BMI< or ≥29.4, a value determined by Classification and Regression Tree analysis. Predictors of DCI and delayed infarction were identified using stepwise multivariate logistic regression analysis. RESULTS There were 161 patients included for analysis. Average BMI within our patient cohort was 28.9, with 67 patients presenting with a BMI of ≥29.4 on admission. DCI occurred in 50 patients (31.1%) and was complicated by delayed infarction in 15 patients (9.3%). On stepwise multivariate analysis, BMI ≥ 29.4 was independently associated with reduced likelihood of DCI (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.18-0.92) and delayed infarction (OR 0.13, 95% CI 0.02-0.61; P = .008). Increasing maximum flow velocity on transcranial Doppler ultrasound was independently associated with increased odds of both DCI (Unit OR 1.19, 95% CI 1.09-1.30; P < .001) and delayed infarction (Unit OR 1.31, 95% CI 1.13-1.56; P < .001), while intracerebral hemorrhage was independently associated with increased odds of delayed infarction (OR 6.99, 95% CI 1.82-30.25; P = .005). CONCLUSION We report an association between elevated BMI and reduced incidence of DCI and delayed infarction, suggesting a protective effect of increasing BMI on the risk of ischemic complications after aSAH. Aneurysmal subarachnoid hemorrhage, Body mass index, Cerebral hemorrhage, Cerebral infarction ABBREVIATIONS ABBREVIATIONS AIC Akaike information criterion aSAH aneurysmal subarachnoid hemorrhage BMI body mass index CART Classification and Regression Tree Analysis CI confidence interval CT computed tomography DCI delayed cerebral ischemia MRI magnetic resonance imaging mRS modified Rankin Scale OR odds ratio TCD transcranial Doppler ultrasound WFNS World Federation of Neurosurgical Societies Delayed cerebral ischemia (DCI) is a major contributor to morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH).1 While potentially reversible, DCI may progress to cerebral infarction, which increases the likelihood of poor functional outcome after aSAH.2-3 The pathophysiology of DCI is complex and not completely understood; there is evidence to suggest that varying predisposition to DCI may exist between different patient populations.4 An obesity paradox has been postulated to occur in patients with cerebral ischemia, specifically a protective effect of elevated BMI with regard to both stroke incidence and severity.5-8 Though the effect of BMI on the clinical course and outcome after aSAH has been investigated previously,9-15 a recent study reported a differential effect of elevated BMI on functional outcomes after aSAH dependent on treatment modality, with greater BMI being associated with better outcomes among patients treated with endovascular coiling.16 Whether or not BMI affects the incidence and severity of DCI after aSAH remains largely unexplored. Herein, we examined the effect of BMI on the incidence of DCI and delayed infarction among a cohort of patients with aSAH treated at our institution. METHODS Patient Selection After approval from our Institutional Review Board, we analyzed our registry of patients with aSAH admitted to our institution and treated with either surgical clipping or endovascular coiling between the years 2009 and 2013. There were 170 patients admitted during this time period. As the incidence of cerebral infarction was determined by review of postoperative computed tomographic (CT) images, patients who were not evaluated with postoperative CT imaging were excluded from analysis (n = 9), leaving a total of 161 patients. Given the retrospective nature of this study, in accordance with our institutional policy, informed consent was not required for the individuals included for analysis. Patients who did not provide a general research consent on admission to the hospital were excluded. Outcomes of Interest The primary outcomes of interest were the incidence of DCI and delayed cerebral infarction. DCI was defined as delayed neurological deterioration after aSAH not due to other causes evident on clinical, laboratory, or radiographic evaluation, as previously described.17 Delayed cerebral infarction was defined as a cerebral hypodensity in an arterial distribution visualized on CT imaging. For each patient, preoperative, immediate postoperative (obtained within 3 d after the procedure to secure the ruptured aneurysm), and delayed CT scans were reviewed. Hypodensities appearing in a delayed fashion that were not present on imaging obtained on admission or within 3 d of aneurysm treatment were considered to represent delayed infarctions. A representative example of delayed infarction can be seen in Figure 1. In patients with suspected delayed infarction, follow-up head CT images obtained after discharge from the hospital were also reviewed to assess for the presence of radiographic changes consistent with evolution of cerebral infarction. Encephalomalacia in the area of the previously seen hypodensity was considered to support the diagnosis of infarction (Figure 1C). Follow-up images were available in 60% (9/15) of patients, and in each case demonstrated changes consistent with infarction. Follow-up images were not available in the remaining 6 patients due to death during admission (n = 4) or loss to follow-up (n = 2). In one of the patients lost to follow-up, magnetic resonance imaging (MRI) of the brain obtained prior to dismissal demonstrated restricted diffusion in the area of suspected infarction. Overall, additional imaging modalities such as MRI and CT perfusion studies providing additional evidence of infarction were available for review in 4 and 4 patients, respectively. Reviewers of imaging studies were blinded to clinical information (including BMI) during evaluation for cerebral hypodensities. FIGURE 1. View largeDownload slide Representative case of a patient suffering a right frontoparietal delayed cerebral infarction. A, CT images obtained prior to aneurysm treatment. B, CT images initially demonstrating the cerebral hypodensity suggesting delayed infarction. C, Images from follow-up CT scans demonstrating persistent hypodensities consistent with cerebral infarction. Text below each panel describes time in days from ictus CT was obtained. PBD, postbleed day. FIGURE 1. View largeDownload slide Representative case of a patient suffering a right frontoparietal delayed cerebral infarction. A, CT images obtained prior to aneurysm treatment. B, CT images initially demonstrating the cerebral hypodensity suggesting delayed infarction. C, Images from follow-up CT scans demonstrating persistent hypodensities consistent with cerebral infarction. Text below each panel describes time in days from ictus CT was obtained. PBD, postbleed day. A secondary outcome of interest was the patient's functional outcome according to the modified Rankin Scale (mRS). For the purpose of this analysis, functional outcome was dichotomized with an mRS ≤ 2 representing good functional outcome. mRS was determined on last follow-up within 1 yr of aSAH. The cut-off of 1 yr was chosen to limit the effect of interim morbidity unrelated to subarachnoid hemorrhage incurred between hospital dismissal and follow-up. Patient Characteristics The primary variable of interest was the patient's BMI, which was calculated from patient height and weight on admission for aSAH. BMI was considered as a categorical variable with patients segregated according to BMI less than or greater than or equal to 29.4. The value of 29.4 was determined by Classification and Regression Tree Analysis (CART). For an independent continuous variable, in this case BMI, CART determines the value above and below which the greatest differences in a dependent variable, in this case incidence of delayed infarction, is seen. Other variables of interest included patient's age, sex, history of hypertension, active smoking at the time of admission, presenting World Federation of Neurosurgical Societies (WFNS) and modified Fisher scores, presence of intracerebral hemorrhage on admission CT imaging, need for external ventricular drainage, aneurysm location and size, treatment modality with clipping or coiling, maximum flow velocity recorded on transcranial Doppler ultrasound (TCD), presence of angiographic vasospasm visualized on CT or digital subtraction angiography, and use of endovascular intervention for the treatment of vasospasm. In general, TCDs were performed every other day starting on postbleed day 3. The maximal velocity recorded across serial examinations was noted. TCDs were either not preformed or unobtainable in 17 of 161 patients. Angiographic vasospasm was defined as a reduction in arterial vessel caliber when compared to vascular imaging obtained on admission for subarachnoid hemorrhage. After aneurysm treatment, vascular imaging in the form of CT or digital subtraction angiography was obtained on an ad hoc basis in response to changes in neurological function to investigate either for vasospasm or continued exclusion of the aneurysm from the cerebral circulation. For the purposes of this study, the determination of angiographic vasospasm was based on the interpretation of the reading radiologist, as well as that of the treating neurosurgeon and neurointensivist. In general, angiographic vasospasm was considered to be present if a clear reduction in vessel wall caliber was evident on comparison of postprocedural vascular imaging to initial imaging studies. Minimal or equivocal reduction in caliber, as judged by the reading radiologist, was not considered to represent angiographic vasospasm. Postprocedural vascular imaging was not obtained in 21 of 161 patients. Endovascular intervention was performed at the discretion of the attending proceduralist depending on the severity of vasospasm present and feasibility of intervention. Intervention was either pharmacologic, consisting of intra-arterial injection of verapamil or papaverine, or mechanical in the form of balloon angioplasty. Statistical Analysis Statistics for continuous and categorical variables were presented as a mean, standard deviation, and range and frequency and percentage, respectively, and compared using the Student's t-test and Pearson's chi-squared test, when appropriate. The relationship of BMI to maximum velocity on TCD was investigated using linear regression analysis, the results of which were presented as an r2- and P-value. Predictors of DCI, delayed infarction, and poor functional outcome were identified using univariate logistic regression analysis. Independent predictors of outcomes of interest were identified using a stepwise multivariate logistic regression model. Angiographic vasospasm was not included in uni- or multivariate regression models due to its strong association and likely multicollinearity with maximal velocity on TCD (see Results). Maximal velocity on TCD was included in favor of angiographic vasospasm given the availability of information on TCD velocities in a greater number of patients. A stepwise model was chosen to reduce the possibility of model overfitting given the relatively small number of patients who suffered delayed infarction, as well as to mitigate potential multicollinearity between predictor variables. All variables associated with the outcome of interest with a P-value of <.10 on univariate analysis were initially included in the multivariate model. Using a backward elimination method, variables with a negligible effect on model fit were removed in stepwise fashion until removal of additional variables resulted in model deterioration. The final iteration of each model was validated with respect to other potential models through the use of the Akaike information criterion (AIC), with the chosen model having the lowest AIC relative to other models. Receiver operating characteristic curves were computed for each multivariate model and C-statistics were provided as a measure of goodness of fit. The alpha level for statistical significance was set at 0.05. Analyses were performed using commercially available software (JMP® 10.0.0, ©2012 SAS Institute Inc, Cary, North Carolina). RESULTS Patient Demographics and Outcomes There were 161 patients who met our inclusion criteria. The mean BMI among this cohort was 28.9, with 67 patients having a BMI ≥ 29.4. There were 38 and 126 patients who presented with a WFNS score ≥3 and a modified Fisher score >2, respectively. Intracerebral hemorrhage was present on initial CT imaging in 37 patients. There were 82 patients who required external ventricular drainage. Mean ruptured aneurysm size was 7.0 mm, with a majority of aneurysms occurring in the anterior circulation (136/161, 81.4%). A majority of patients were treated with endovascular coiling (127/161, 78.9%). The mean maximal velocity detected on TCD was 109.6 cm/s. Angiographic vasospasm was detected in 58 of the 141 (41.1%) patients who underwent vascular imaging after aneurysm treatment, with 19 patients (11.8%) receiving either pharmacologic (n = 10, 6.2%) or mechanical (n = 9, 5.6%) endovascular therapy for vasospasm. Maximal velocity on TCD was significantly greater in patients with angiographic vasospasm (137.0 cm/s vs 85.7 cm/s; P < .001) and who underwent endovascular treatment of vasospasm (145.6 cm/s vs 104.2 cm/s; P < .001). DCI occurred in 50 patients (31.1%), with 15 of these patients suffering delayed cerebral infarction (9.3%). In patients with delayed infarction, CT scans initially demonstrating evidence of infarction were obtained at a mean time of 9.7 d after surgery (standard deviation [SD]: 2.8, range: 5-16). These images were compared to initial postoperative scans, which were obtained at a mean time of 1.5 d after surgery (SD: 1.0, range: 0-3). Maximum velocity on TCD was significantly greater in patients with delayed infarction relative to patients without infarction (160.2 cm/s vs 104.2 cm/s; P < .001). Among patients with delayed infarction, 13 (86.7%) underwent postprocedural vascular imaging, with imaging demonstrating evidence of arterial vasospasm in 12 patients (92.3%). On average, these images were obtained 2.0 d (SD: 2.4) from the date on which the delayed infarct was first noted on CT imaging. Endovascular treatment of vasospasm was pursued with greater frequency in patients who ultimately developed delayed infarction (53.3% vs 7.5%; P < .001), with 3 and 5 patients who suffered delayed infarction undergoing pharmacologic and mechanical intervention, respectively. Patients with BMI ≥ 29.4 were less likely to experience DCI (20.9% vs 38.3%; P = .019) or delayed infarction (3.0% vs 13.8%; P = .013). There were no other significant differences between patients with low and high BMI (Table 1). There were 44 patients with poor functional outcome on follow-up. The mean time to follow-up from hospital admission was 146.2 d (SD: 91.1). The complete list of patient characteristics and outcomes is presented in Table 1. TABLE 1. Patient Characteristics and Outcomes Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  BMI, body mass index; TCD, transcranial Doppler, WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aTCDs obtained on 144/161 patients. bPostprocedural vascular imaging obtained on 139/161 patients. cTime of last follow-up for patients who died during admission for subarachnoid hemorrhage was not included the calculation of mean follow-up time. View Large TABLE 1. Patient Characteristics and Outcomes Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  BMI, body mass index; TCD, transcranial Doppler, WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aTCDs obtained on 144/161 patients. bPostprocedural vascular imaging obtained on 139/161 patients. cTime of last follow-up for patients who died during admission for subarachnoid hemorrhage was not included the calculation of mean follow-up time. View Large Predictors of DCI, Delayed Infarction, and Poor Functional Outcome Predictors of DCI and delayed infarction were then identified using univariate logistic regression analysis. BMI ≥ 29.4 (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20-0.86; P = .017) and presence of the aneurysm within the anterior circulation (OR 0.26, 95% CI 0.06-0.79; P = .016) were associated with a reduced likelihood of DCI. Severe WFNS (OR 2.56, 95% CI 1.20-5.46; P = .015) and modified Fisher scores (OR 2.59, 95% CI 1.06-7.34; P = .036), intracerebral hemorrhage (OR 2.72, 95% CI 1.27-5.86; P = .010), and increasing maximum velocity on TCD (Unit OR 1.19, 95% CI 1.10-1.30; P < .001) were associated with increased likelihood of DCI. BMI ≥ 29.4 was associated with reduced odds of delayed infarction (OR 0.19, 95% CI 0.03-0.73; P = .013). Predictors of delayed infarction were similar to those of DCI, as severe WFNS (OR 4.42, 95% CI 1.47-13.56; P = .009) and modified Fisher scores (OR NA [see text]; P = .036), intracerebral hemorrhage (OR 6.32, 95% CI 2.11-20.27; P = .001), and increasing maximum velocity on TCD (Unit OR 1.30, 95% CI 1.14-1.52; P < .001) were associated with increased likelihood of delayed infarction. The complete results of univariate analyses are presented in Table 2. TABLE 2. Univariate Logistic Regression Analysis Indicating Predictors of Delayed Cerebral Ischemia and Delayed Hypodensities Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  BMI, body mass index; DCI, delayed cerebral ischemia; TCD, transcranial Doppler; WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 1 unit increase in age and aneurysm size and every 10 unit increase in maximum velocity on TCD. bAs every patient with delayed cerebral hypodensities was diagnosed with delayed cerebral ischemia, DCI was not included in this univariate analysis. cAn OR could not be calculated as all patients with delayed hypodensities presented with a Modified Fisher score > 2. View Large TABLE 2. Univariate Logistic Regression Analysis Indicating Predictors of Delayed Cerebral Ischemia and Delayed Hypodensities Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  BMI, body mass index; DCI, delayed cerebral ischemia; TCD, transcranial Doppler; WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 1 unit increase in age and aneurysm size and every 10 unit increase in maximum velocity on TCD. bAs every patient with delayed cerebral hypodensities was diagnosed with delayed cerebral ischemia, DCI was not included in this univariate analysis. cAn OR could not be calculated as all patients with delayed hypodensities presented with a Modified Fisher score > 2. View Large On multivariate stepwise analysis, BMI ≥ 29.4 remained associated with reduced likelihood of DCI (OR 0.42, 95% CI 0.18-0.92). Increasing maximum velocity on TCD was independently associated with an increased likelihood of DCI (Unit OR 1.19, 95% CI 1.09-1.30; P < .001). BMI ≥ 29.4 was also independently associated with reduced odds of delayed cerebral infarction (OR 0.13, 95% CI 0.02-0.61; P = .008). Intracerebral hemorrhage (OR 6.99, 95% CI 1.82-30.25; P = .005) and increasing maximum velocity on TCD (Unit OR 1.31, 95% CI 1.13-1.56; P < .001) were independently associated with increased odds of delayed infarction (Table 3). TABLE 3. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of DCI and Delayed Infraction Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 10 cm/s increase in maximum velocity on TCD. View Large TABLE 3. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of DCI and Delayed Infraction Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 10 cm/s increase in maximum velocity on TCD. View Large We also examined whether BMI was associated with poor functional outcome. On univariate analysis, BMI ≥ 29.4 was not associated with poor functional outcome (OR 0.74, 95% CI 0.36-1.50; P = .41). Both DCI (OR 3.65, 95% CI 1.77-7.66; P < .001) and delayed infarction (OR 4.76, 95% CI 1.61-15.09; P = .005), however, were associated with increased odds of poor functional outcome (Table 4). TABLE 4. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of Poor Functional Outcome (Modified Rankin Scale > 2) Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. View Large TABLE 4. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of Poor Functional Outcome (Modified Rankin Scale > 2) Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. View Large Relationship of BMI to TCD Velocities and Incidence of Angiographic Vasospasm We then investigated whether an association was present between patient BMI and maximum velocity on TCD. On linear regression analysis, there was no relationship between BMI and maximum velocity on TCD (r2 = 0.001; Figure 2). There was also no difference in average maximum velocity between patients with BMI < 29.4 and those with BMI ≥ 29.4 (113.1 vs 105.1; P = .16). Angiographic vasospasm occurred in similar frequencies between patients with BMI < 29.4 and ≥ 29.4 (43.2% vs 39.7%; P = .68). FIGURE 2. View largeDownload slide Linear regression analysis of relationship of BMI to maximal velocity on TCD. The graph depicts maximal velocity on TCD as a function of patient BMI, with the blue line depicting the relationship determined by linear regression analysis. Shaded areas denote 95% CIs. BMI, body mass index; TCD, transcranial Doppler. FIGURE 2. View largeDownload slide Linear regression analysis of relationship of BMI to maximal velocity on TCD. The graph depicts maximal velocity on TCD as a function of patient BMI, with the blue line depicting the relationship determined by linear regression analysis. Shaded areas denote 95% CIs. BMI, body mass index; TCD, transcranial Doppler. DISCUSSION In the present study, we describe an association between increased BMI and reduced incidence of both DCI and subsequent delayed cerebral infarction after aSAH. These results suggest a mechanism through which increased BMI may contribute to improved functional outcome after aSAH.10,16 Relationship of BMI to Outcomes After Subarachnoid Hemorrhage While we observed a significant association between BMI and delayed ischemia, we did not observe an association of BMI with patient functional outcomes. The effect of BMI on outcomes after aSAH remains controversial, with conflicting results reported previously in the literature.9-16 A recent study suggests that the effect of BMI on outcomes after aSAH may depend on treatment modality, with increased BMI conferring a positive and negative effect in patients treated with coiling versus clipping, respectively.16 Obesity may increase the risks of surgery in general18 and intracranial surgery in particular.19 As such, a beneficial effect of BMI may be more likely to manifest only in patients treated with endovascular coiling, and possibly in patients at higher risk of DCI. Moreover, previous large-scale studies have found differing of BMI on patient outcomes when stratified by the degree of obesity, with potential benefit observed in patients with mild as opposed to morbid obesity.9 To better understand how BMI influences the prognosis of patients after aneurysm rupture, additional, more quantitative studies investigating how BMI affects the incidence of different forms of both neurological and nonneurological morbidity are needed. Mechanism of Effect of BMI on Incidence of Delayed Infarcts The mechanism by which increased BMI may be protective against delayed ischemia is not immediately clear. We did not observe an association of BMI with maximal velocities measured on serial TCD examinations or with the incidence of angiographic vasospasm among patients who underwent vascular imaging after aneurysm treatment, though it is known that the correlation between the detection of vasospasm by TCD or angiography and the occurrence of cerebral ischemia (defined as either DCI or cerebral infarction) is suboptimal.20 It has been proposed that vasospasm alone is not sufficient to produce DCI,21 the pathophysiology of which is complex and multifactorial.4 It is possible that obesity confers resistance to neuronal dysfunction in the setting of ischemia. For example, leptin, a hormone produced by adipocytes involved in the regulation of satiety, has been shown in vitro to have protective effects against cerebral ischemia.22-24 Of note, however, obesity has been associated with leptin resistance within the central nervous system.25 Obesity has also been associated with remodeling of the cerebral vasculature, specifically intimal and medial thickening secondary to impaired nitric oxide-mediated signaling pathways.26 Interestingly, DCI may result in part from impaired nitric oxide-mediated vasodilatation, leading to pial vessel vasoconstriction in response to hemorrhage on the cortical surface.4 It is possible that reduced dependence on nitric oxide-dependent pathways confers resistance to DCI. On the other hand, baseline impairment of compensatory vasodilation could alternatively predispose to neurological deterioration in response to cerebral ischemia. Further investigation into the cellular and molecular effects of increased BMI, and how they may translate into cerebral protection in the setting of aSAH is warranted. Relationship of Intracerebral Hemorrhage to Incidence of Delayed Infarction We also observed an independent association between intracerebral hemorrhage on presentation with aSAH and the incidence of delayed cerebral infarction. Previous studies have described an association of intracerebral hemorrhage with both DCI27-28 and poor functional outcome29 after aSAH. Our results provide further evidence of the prognostic significance of intraparenchymal hemorrhage resulting from aneurysmal rupture. Limitations Our study is limited by the relatively small sample size, in particular the small number of delayed infarctions. Larger studies will be needed to confirm our results. An additional limitation is our retrospective and single-center methodology. Specifically, though each patient within our cohort underwent at least 1 immediate postprocedural and delayed CT scan, images were nevertheless obtained when warranted by clinical circumstances and at the discretion of the treating team. As such, it is possible that clinically silent infarctions were missed, which could explain the reduced incidence of delayed infarction observed in our study when compared to previous cohorts treated at our institution.20,30 Moreover, CT imaging is not the most sensitive modality to detect cerebral infarction. While we reviewed all available CT scans, including those obtained after discharge, to support the determination of infarction, it is possible that some patients were incorrectly categorized as suffering infarction or that some infarctions were missed due to the limitations of CT imaging. Adjunct imaging techniques with increased sensitivity for ischemia, such as MRI and CT perfusion, were obtained in only a minority of patients, and thus future studies may benefit from the scheduled use of these techniques to assess for infarction. Infarcts were considered to be delayed if they were not present on head CT imaging obtained within 3 d of surgical intervention. Though images first demonstrating evidence of delayed infarction were obtained at an average of 9.7 d after initial surgery, it is possible that in certain cases infarcts occurring in the perioperative period were simply not detected until later in the patient's clinical course due to the limited sensitivity and inconsistent timing of CT imaging. Again, future studies utilizing the scheduled use of more sensitive imaging techniques both during and after the perioperative period may be needed to confirm the association of increased BMI and delayed infarction. Maximal velocity on TCD in any vessel was recorded for each patient. While increasing velocity was well correlated with both angiographic vasospasm and the incidence of delayed infarction, lower velocities may nevertheless represent significant vasospasm in certain areas of the Circle of Willis, particularly the posterior circulation. To better understand the mechanism by which BMI may lead to DCI and subsequent infarction, a more in-depth analysis of TCDs with cut-offs specific to different arterial locations may be needed. Finally, the variables included in our multivariate analysis are almost certainly inter-related to a certain degree, and thus multicollinearity may have influenced the observed association of individual predictors to outcomes of interest. Our findings require confirmation in future studies. CONCLUSION We describe an association with increased BMI and delayed neurological deterioration and subsequent cerebral infarction after aSAH. These results provide a potential explanation for how elevated BMI may predispose to improved functional outcomes after aSAH. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Dorhout Mees SM, Kerr RS, Rinkel GJ, Algra A, Molyneux AJ. Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT). J Neurol . 2012; 259( 4): 679- 683. Google Scholar CrossRef Search ADS PubMed  2. Giraldo EA, Mandrekar JN, Rubin MN et al.   Timing of clinical grade assessment and poor outcome in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg . 2012; 117( 1): 15- 19. Google Scholar CrossRef Search ADS PubMed  3. Pegoli M, Mandrekar J, Rabinstein AA, Lanzino G. Predictors of excellent functional outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg . 2015; 122( 2): 414- 418. Google Scholar CrossRef Search ADS PubMed  4. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol . 2014; 10( 1): 44- 58. Google Scholar CrossRef Search ADS PubMed  5. Andersen KK, Olsen TS. Body mass index and stroke: overweight and obesity less often associated with stroke recurrence. J Stroke Cerebrovasc Dis . 2013; 22( 8): e576- e581. Google Scholar CrossRef Search ADS PubMed  6. Andersen KK, Olsen TS. The obesity paradox in stroke: lower mortality and lower risk of readmission for recurrent stroke in obese stroke patients. Int J Stroke . 2015; 10( 1): 99- 104. Google Scholar CrossRef Search ADS PubMed  7. Jackson RS, Black JH III, Lum YW et al.   Class I obesity is paradoxically associated with decreased risk of postoperative stroke after carotid endarterectomy. J Vasc Surg . 2012; 55( 5): 1306- 1312. Google Scholar CrossRef Search ADS PubMed  8. Volkers EJ, Greving JP, Hendrikse J et al.   Body mass index and outcome after revascularization for symptomatic carotid artery stenosis. Neurology . 2017; 88( 21): 2052- 2060. Google Scholar CrossRef Search ADS PubMed  9. Dasenbrock HH, Nguyen MO, Frerichs KU et al.   The impact of body habitus on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis. J Neurosurg . 2017; 127( 1): 36- 46. Google Scholar CrossRef Search ADS PubMed  10. Hughes JD, Samarage M, Burrows AM, Lanzino G, Rabinstein AA. Body mass index and aneurysmal subarachnoid hemorrhage: decreasing mortality with increasing body mass index. World Neurosurg . 2015; 84( 6): 1598- 1604. Google Scholar CrossRef Search ADS PubMed  11. Juvela S, Siironen J, Kuhmonen J. Hyperglycemia, excess weight, and history of hypertension as risk factors for poor outcome and cerebral infarction after aneurysmal subarachnoid hemorrhage. J Neurosurg . 2005; 102( 6): 998- 1003. Google Scholar CrossRef Search ADS PubMed  12. Kagerbauer SM, Kemptner DM, Schepp CP et al.   Elevated premorbid body mass index is not associated with poor neurological outcome in the subacute state after aneurysmal subarachnoid hemorrhage. Cen Eur Neurosurg . 2010; 71( 4): 163- 166. Google Scholar CrossRef Search ADS   13. Sandvei MS, Mathiesen EB, Vatten LJ et al.   Incidence and mortality of aneurysmal subarachnoid hemorrhage in two Norwegian cohorts, 1984-2007. Neurology . 2011; 77( 20): 1833- 1839. Google Scholar CrossRef Search ADS PubMed  14. Schultheiss KE, Jang YG, Yanowitch RN et al.   Fat and neurosurgery: Does obesity affect outcome after intracranial surgery? Neurosurgery . 2009; 64( 2): 316- 327. Google Scholar CrossRef Search ADS PubMed  15. Yamada S, Koizumi A, Iso H et al.   Risk factors for fatal subarachnoid hemorrhage: the Japan Collaborative Cohort Study. Stroke . 2003; 34( 12): 2781- 2787. Google Scholar CrossRef Search ADS PubMed  16. Rinaldo L, Hughes JD, Rabinstein AA, Lanzino G. Effect of body mass index on outcome after aneurysmal subarachnoid hemorrhage treated with clipping versus coiling. J Neurosurg . 2017: 1- 12. doi: 10.3171/2017.4.JNS17557. [published online ahead of print]. 17. Vergouwen MD, Vermeulen M, van Gijn J et al.   Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke . 2010; 41( 10): 2391- 2395. Google Scholar CrossRef Search ADS PubMed  18. Stevens SM, O’Connell BP, Meyer TA. Obesity related complications in surgery. Curr Opin Otolaryngol Head Neck Surg . 2015; 23( 5): 341- 347. Google Scholar CrossRef Search ADS PubMed  19. Murphy ME, McCutcheon BA, Kerezoudis P et al.   Morbid obesity increases risk of morbidity and reoperation in resection of benign cranial nerve neoplasms. Clin Neurol Neurosurg . 2016; 148: 105- 109. Google Scholar CrossRef Search ADS PubMed  20. Rabinstein AA, Friedman JA, Weigand SD et al.   Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke . 2004; 35( 8): 1862- 1866. Google Scholar CrossRef Search ADS PubMed  21. Crowley RW, Medel R, Dumont AS et al.   Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke . 2011; 42( 4): 919- 923. Google Scholar CrossRef Search ADS PubMed  22. Zhang F, Wang S, Signore AP, Chen J. Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia. Stroke . 2007; 38( 8): 2329- 2336. Google Scholar CrossRef Search ADS PubMed  23. Zhang JY, Yan GT, Liao J et al.   Leptin attenuates cerebral ischemia/reperfusion injury partially by CGRP expression. Eur J Pharmacol . 2011; 671( 1-3): 61- 69. Google Scholar CrossRef Search ADS PubMed  24. Zhang Z, Deng Z, Liao J et al.   Leptin attenuates cerebral ischemia injury through the promotion of energy metabolism via the PI3K/Akt pathway. J Cereb Blood Flow Metab . 2013; 33( 4): 567- 574. Google Scholar CrossRef Search ADS PubMed  25. Davis C, Mudd J, Hawkins M. Neuroprotective effects of leptin in the context of obesity and metabolic disorders. Neurobiol Dis . 2014; 72: 61- 71. Google Scholar CrossRef Search ADS PubMed  26. Dorrance AM, Matin N, Pires PW. The effects of obesity on the cerebral vasculature. Curr Vasc Pharmacol . 2014; 12( 3): 462- 472. Google Scholar CrossRef Search ADS PubMed  27. Crobeddu E, Mittal MK, Dupont S, Wijdicks EF, Lanzino G, Rabinstein AA. Predicting the lack of development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke . 2012; 43( 3): 697- 701. Google Scholar CrossRef Search ADS PubMed  28. Platz J, Güresir E, Wagner M, Seifert V, Konczalla J. Increased risk of delayed cerebral ischemia in subarachnoid hemorrhage patients with additional intracerebral hematoma. J Neurosurg . 2017; 126( 2): 504- 510. Google Scholar CrossRef Search ADS PubMed  29. Wan A, Jaja BN, Schweizer TA et al.   Clinical characteristics and outcome of aneurysmal subarachnoid hemorrhage with intracerebral hematoma. J Neurosurg . 2016; 125( 6): 1344- 1351. Google Scholar CrossRef Search ADS PubMed  30. Rabinstein AA, Weigand S, Atkinson JL, Wijdicks EF. Patterns of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke . 2005; 36( 5): 992- 997. Google Scholar CrossRef Search ADS PubMed  Copyright © 2018 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Increased Body Mass Index Associated With Reduced Risk of Delayed Cerebral Ischemia and Subsequent Infarction After Aneurysmal Subarachnoid Hemorrhage

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Oxford University Press
Copyright
Copyright © 2018 by the Congress of Neurological Surgeons
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0148-396X
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1524-4040
D.O.I.
10.1093/neuros/nyy104
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Abstract

Abstract BACKGROUND Increased body mass index (BMI) may be protective against cerebral ischemia in certain clinical contexts. OBJECTIVE To investigate whether increased BMI was associated with delayed cerebral ischemia (DCI) and subsequent infarction after aneurysmal subarachnoid hemorrhage (aSAH). METHODS We retrospectively reviewed the clinical course of patients presenting to our institution for management of aSAH. Patient were segregated according to BMI< or ≥29.4, a value determined by Classification and Regression Tree analysis. Predictors of DCI and delayed infarction were identified using stepwise multivariate logistic regression analysis. RESULTS There were 161 patients included for analysis. Average BMI within our patient cohort was 28.9, with 67 patients presenting with a BMI of ≥29.4 on admission. DCI occurred in 50 patients (31.1%) and was complicated by delayed infarction in 15 patients (9.3%). On stepwise multivariate analysis, BMI ≥ 29.4 was independently associated with reduced likelihood of DCI (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.18-0.92) and delayed infarction (OR 0.13, 95% CI 0.02-0.61; P = .008). Increasing maximum flow velocity on transcranial Doppler ultrasound was independently associated with increased odds of both DCI (Unit OR 1.19, 95% CI 1.09-1.30; P < .001) and delayed infarction (Unit OR 1.31, 95% CI 1.13-1.56; P < .001), while intracerebral hemorrhage was independently associated with increased odds of delayed infarction (OR 6.99, 95% CI 1.82-30.25; P = .005). CONCLUSION We report an association between elevated BMI and reduced incidence of DCI and delayed infarction, suggesting a protective effect of increasing BMI on the risk of ischemic complications after aSAH. Aneurysmal subarachnoid hemorrhage, Body mass index, Cerebral hemorrhage, Cerebral infarction ABBREVIATIONS ABBREVIATIONS AIC Akaike information criterion aSAH aneurysmal subarachnoid hemorrhage BMI body mass index CART Classification and Regression Tree Analysis CI confidence interval CT computed tomography DCI delayed cerebral ischemia MRI magnetic resonance imaging mRS modified Rankin Scale OR odds ratio TCD transcranial Doppler ultrasound WFNS World Federation of Neurosurgical Societies Delayed cerebral ischemia (DCI) is a major contributor to morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH).1 While potentially reversible, DCI may progress to cerebral infarction, which increases the likelihood of poor functional outcome after aSAH.2-3 The pathophysiology of DCI is complex and not completely understood; there is evidence to suggest that varying predisposition to DCI may exist between different patient populations.4 An obesity paradox has been postulated to occur in patients with cerebral ischemia, specifically a protective effect of elevated BMI with regard to both stroke incidence and severity.5-8 Though the effect of BMI on the clinical course and outcome after aSAH has been investigated previously,9-15 a recent study reported a differential effect of elevated BMI on functional outcomes after aSAH dependent on treatment modality, with greater BMI being associated with better outcomes among patients treated with endovascular coiling.16 Whether or not BMI affects the incidence and severity of DCI after aSAH remains largely unexplored. Herein, we examined the effect of BMI on the incidence of DCI and delayed infarction among a cohort of patients with aSAH treated at our institution. METHODS Patient Selection After approval from our Institutional Review Board, we analyzed our registry of patients with aSAH admitted to our institution and treated with either surgical clipping or endovascular coiling between the years 2009 and 2013. There were 170 patients admitted during this time period. As the incidence of cerebral infarction was determined by review of postoperative computed tomographic (CT) images, patients who were not evaluated with postoperative CT imaging were excluded from analysis (n = 9), leaving a total of 161 patients. Given the retrospective nature of this study, in accordance with our institutional policy, informed consent was not required for the individuals included for analysis. Patients who did not provide a general research consent on admission to the hospital were excluded. Outcomes of Interest The primary outcomes of interest were the incidence of DCI and delayed cerebral infarction. DCI was defined as delayed neurological deterioration after aSAH not due to other causes evident on clinical, laboratory, or radiographic evaluation, as previously described.17 Delayed cerebral infarction was defined as a cerebral hypodensity in an arterial distribution visualized on CT imaging. For each patient, preoperative, immediate postoperative (obtained within 3 d after the procedure to secure the ruptured aneurysm), and delayed CT scans were reviewed. Hypodensities appearing in a delayed fashion that were not present on imaging obtained on admission or within 3 d of aneurysm treatment were considered to represent delayed infarctions. A representative example of delayed infarction can be seen in Figure 1. In patients with suspected delayed infarction, follow-up head CT images obtained after discharge from the hospital were also reviewed to assess for the presence of radiographic changes consistent with evolution of cerebral infarction. Encephalomalacia in the area of the previously seen hypodensity was considered to support the diagnosis of infarction (Figure 1C). Follow-up images were available in 60% (9/15) of patients, and in each case demonstrated changes consistent with infarction. Follow-up images were not available in the remaining 6 patients due to death during admission (n = 4) or loss to follow-up (n = 2). In one of the patients lost to follow-up, magnetic resonance imaging (MRI) of the brain obtained prior to dismissal demonstrated restricted diffusion in the area of suspected infarction. Overall, additional imaging modalities such as MRI and CT perfusion studies providing additional evidence of infarction were available for review in 4 and 4 patients, respectively. Reviewers of imaging studies were blinded to clinical information (including BMI) during evaluation for cerebral hypodensities. FIGURE 1. View largeDownload slide Representative case of a patient suffering a right frontoparietal delayed cerebral infarction. A, CT images obtained prior to aneurysm treatment. B, CT images initially demonstrating the cerebral hypodensity suggesting delayed infarction. C, Images from follow-up CT scans demonstrating persistent hypodensities consistent with cerebral infarction. Text below each panel describes time in days from ictus CT was obtained. PBD, postbleed day. FIGURE 1. View largeDownload slide Representative case of a patient suffering a right frontoparietal delayed cerebral infarction. A, CT images obtained prior to aneurysm treatment. B, CT images initially demonstrating the cerebral hypodensity suggesting delayed infarction. C, Images from follow-up CT scans demonstrating persistent hypodensities consistent with cerebral infarction. Text below each panel describes time in days from ictus CT was obtained. PBD, postbleed day. A secondary outcome of interest was the patient's functional outcome according to the modified Rankin Scale (mRS). For the purpose of this analysis, functional outcome was dichotomized with an mRS ≤ 2 representing good functional outcome. mRS was determined on last follow-up within 1 yr of aSAH. The cut-off of 1 yr was chosen to limit the effect of interim morbidity unrelated to subarachnoid hemorrhage incurred between hospital dismissal and follow-up. Patient Characteristics The primary variable of interest was the patient's BMI, which was calculated from patient height and weight on admission for aSAH. BMI was considered as a categorical variable with patients segregated according to BMI less than or greater than or equal to 29.4. The value of 29.4 was determined by Classification and Regression Tree Analysis (CART). For an independent continuous variable, in this case BMI, CART determines the value above and below which the greatest differences in a dependent variable, in this case incidence of delayed infarction, is seen. Other variables of interest included patient's age, sex, history of hypertension, active smoking at the time of admission, presenting World Federation of Neurosurgical Societies (WFNS) and modified Fisher scores, presence of intracerebral hemorrhage on admission CT imaging, need for external ventricular drainage, aneurysm location and size, treatment modality with clipping or coiling, maximum flow velocity recorded on transcranial Doppler ultrasound (TCD), presence of angiographic vasospasm visualized on CT or digital subtraction angiography, and use of endovascular intervention for the treatment of vasospasm. In general, TCDs were performed every other day starting on postbleed day 3. The maximal velocity recorded across serial examinations was noted. TCDs were either not preformed or unobtainable in 17 of 161 patients. Angiographic vasospasm was defined as a reduction in arterial vessel caliber when compared to vascular imaging obtained on admission for subarachnoid hemorrhage. After aneurysm treatment, vascular imaging in the form of CT or digital subtraction angiography was obtained on an ad hoc basis in response to changes in neurological function to investigate either for vasospasm or continued exclusion of the aneurysm from the cerebral circulation. For the purposes of this study, the determination of angiographic vasospasm was based on the interpretation of the reading radiologist, as well as that of the treating neurosurgeon and neurointensivist. In general, angiographic vasospasm was considered to be present if a clear reduction in vessel wall caliber was evident on comparison of postprocedural vascular imaging to initial imaging studies. Minimal or equivocal reduction in caliber, as judged by the reading radiologist, was not considered to represent angiographic vasospasm. Postprocedural vascular imaging was not obtained in 21 of 161 patients. Endovascular intervention was performed at the discretion of the attending proceduralist depending on the severity of vasospasm present and feasibility of intervention. Intervention was either pharmacologic, consisting of intra-arterial injection of verapamil or papaverine, or mechanical in the form of balloon angioplasty. Statistical Analysis Statistics for continuous and categorical variables were presented as a mean, standard deviation, and range and frequency and percentage, respectively, and compared using the Student's t-test and Pearson's chi-squared test, when appropriate. The relationship of BMI to maximum velocity on TCD was investigated using linear regression analysis, the results of which were presented as an r2- and P-value. Predictors of DCI, delayed infarction, and poor functional outcome were identified using univariate logistic regression analysis. Independent predictors of outcomes of interest were identified using a stepwise multivariate logistic regression model. Angiographic vasospasm was not included in uni- or multivariate regression models due to its strong association and likely multicollinearity with maximal velocity on TCD (see Results). Maximal velocity on TCD was included in favor of angiographic vasospasm given the availability of information on TCD velocities in a greater number of patients. A stepwise model was chosen to reduce the possibility of model overfitting given the relatively small number of patients who suffered delayed infarction, as well as to mitigate potential multicollinearity between predictor variables. All variables associated with the outcome of interest with a P-value of <.10 on univariate analysis were initially included in the multivariate model. Using a backward elimination method, variables with a negligible effect on model fit were removed in stepwise fashion until removal of additional variables resulted in model deterioration. The final iteration of each model was validated with respect to other potential models through the use of the Akaike information criterion (AIC), with the chosen model having the lowest AIC relative to other models. Receiver operating characteristic curves were computed for each multivariate model and C-statistics were provided as a measure of goodness of fit. The alpha level for statistical significance was set at 0.05. Analyses were performed using commercially available software (JMP® 10.0.0, ©2012 SAS Institute Inc, Cary, North Carolina). RESULTS Patient Demographics and Outcomes There were 161 patients who met our inclusion criteria. The mean BMI among this cohort was 28.9, with 67 patients having a BMI ≥ 29.4. There were 38 and 126 patients who presented with a WFNS score ≥3 and a modified Fisher score >2, respectively. Intracerebral hemorrhage was present on initial CT imaging in 37 patients. There were 82 patients who required external ventricular drainage. Mean ruptured aneurysm size was 7.0 mm, with a majority of aneurysms occurring in the anterior circulation (136/161, 81.4%). A majority of patients were treated with endovascular coiling (127/161, 78.9%). The mean maximal velocity detected on TCD was 109.6 cm/s. Angiographic vasospasm was detected in 58 of the 141 (41.1%) patients who underwent vascular imaging after aneurysm treatment, with 19 patients (11.8%) receiving either pharmacologic (n = 10, 6.2%) or mechanical (n = 9, 5.6%) endovascular therapy for vasospasm. Maximal velocity on TCD was significantly greater in patients with angiographic vasospasm (137.0 cm/s vs 85.7 cm/s; P < .001) and who underwent endovascular treatment of vasospasm (145.6 cm/s vs 104.2 cm/s; P < .001). DCI occurred in 50 patients (31.1%), with 15 of these patients suffering delayed cerebral infarction (9.3%). In patients with delayed infarction, CT scans initially demonstrating evidence of infarction were obtained at a mean time of 9.7 d after surgery (standard deviation [SD]: 2.8, range: 5-16). These images were compared to initial postoperative scans, which were obtained at a mean time of 1.5 d after surgery (SD: 1.0, range: 0-3). Maximum velocity on TCD was significantly greater in patients with delayed infarction relative to patients without infarction (160.2 cm/s vs 104.2 cm/s; P < .001). Among patients with delayed infarction, 13 (86.7%) underwent postprocedural vascular imaging, with imaging demonstrating evidence of arterial vasospasm in 12 patients (92.3%). On average, these images were obtained 2.0 d (SD: 2.4) from the date on which the delayed infarct was first noted on CT imaging. Endovascular treatment of vasospasm was pursued with greater frequency in patients who ultimately developed delayed infarction (53.3% vs 7.5%; P < .001), with 3 and 5 patients who suffered delayed infarction undergoing pharmacologic and mechanical intervention, respectively. Patients with BMI ≥ 29.4 were less likely to experience DCI (20.9% vs 38.3%; P = .019) or delayed infarction (3.0% vs 13.8%; P = .013). There were no other significant differences between patients with low and high BMI (Table 1). There were 44 patients with poor functional outcome on follow-up. The mean time to follow-up from hospital admission was 146.2 d (SD: 91.1). The complete list of patient characteristics and outcomes is presented in Table 1. TABLE 1. Patient Characteristics and Outcomes Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  BMI, body mass index; TCD, transcranial Doppler, WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aTCDs obtained on 144/161 patients. bPostprocedural vascular imaging obtained on 139/161 patients. cTime of last follow-up for patients who died during admission for subarachnoid hemorrhage was not included the calculation of mean follow-up time. View Large TABLE 1. Patient Characteristics and Outcomes Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  Variable  BMI < 29.4 (n = 94)  BMI ≥ 29.4 (n = 67)  All patients (n = 161)  P-Value  Age, mean (SD)  55.1 (14.2)  54.1 (11.9)  54.7 (13.2)     Range  19-87  26-82  19-87  .63  Sex, N (%)     Male  34 (36.2)  21 (31.3)  55 (34.2)     Female  60 (63.8)  46 (68.7)  106 (65.8)  .52  BMI  24.4 (3.1)  35.1 (6.0)  28.9 (7.0)     Range  16.9-29.3  29.4-60.9  (16.9-60.9)  <.001  Hypertension     No  47 (50.0)  27 (40.3)  87 (54.0)     Yes  47 (50.0)  40 (59.7)  74 (46.0)  .22  Smoker on Admission     No  47 (50.0)  39 (58.2)  86 (53.4)     Yes  47 (50.0)  28 (41.8)  75 (46.6)  .30  WFNS Score     1-3  70 (74.5)  53 (79.1)  123 (76.4)     4-5  24 (25.5)  14 (20.9)  38 (23.6)  .49  Modified Fisher Score     1-2  21 (22.3)  14 (20.9)  35 (21.7)     3-4  73 (77.7)  53 (79.1)  126 (78.3)  .83  Intracerebral Hemorrhage     No  73 (77.7)  51 (76.1)  124 (77.0)     Yes  21 (22.3)  16 (23.9)  37 (23.0)  .82  External Ventricular Drainage     No  48 (51.1)  31 (46.3)  79 (49.1)     Yes  46 (48.9)  36 (53.7)  82 (50.9)  .55  Aneurysm Size (mm)  7.0 (4.8)  7.1 (4.7)  7.0 (4.8)     Range  1.0-25.0  2.0-21.0  (1.0-25.0)  .89  Aneurysm Location     Anterior Circulation  80 (85.1)  56 (83.6)  136 (84.5)     Posterior Circulation  14 (14.9)  11 (16.4)  25 (15.5)  .79  Treatment Modality     Coiling  76 (80.9)  51 (76.2)  127 (78.9)     Clipping  18 (19.1)  16 (23.9)  34 (21.1)  .47  Maximum Velocity on TCD (cm/s)a  113.1 (46.5)  105.1 (47.0)  109.6 (46.7)     Range  34-230  34-211  (34-230)  .31  Angiographic Vasospasmb     No  46 (56.8)  35 (43.2)  81 (58.2)     Yes  35 (43.2)  23 (39.7)  58 (41.7)  .68  Endovascular Treatment of Vasospasm     No  79 (84.0)  63 (94.0)  142 (88.2)     Yes  15 (16.0)  4 (6.0)  19 (11.8)  .053  Delayed Cerebral Ischemia     No  58 (61.7)  53 (79.1)  111 (68.9)     Yes  36 (38.3)  14 (20.9)  50 (31.1)  .019  Delayed Infarction     No  81 (86.2)  65 (97.0)  146 (90.7)     Yes  13 (13.8)  2 (3.0)  15 (9.3)  .020  Modified Rankin Scale > 2     No  66 (70.2)  51 (76.1)  117 (72.7)     Yes  28 (29.8)  16 (23.9)  44 (27.3)  .41  Mean Follow-up time (d)c  150.6 (94.6)  140.6 (86.7)  146.2 (91.1)     Range  6-354  6-352  (6-354)  .51  BMI, body mass index; TCD, transcranial Doppler, WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aTCDs obtained on 144/161 patients. bPostprocedural vascular imaging obtained on 139/161 patients. cTime of last follow-up for patients who died during admission for subarachnoid hemorrhage was not included the calculation of mean follow-up time. View Large Predictors of DCI, Delayed Infarction, and Poor Functional Outcome Predictors of DCI and delayed infarction were then identified using univariate logistic regression analysis. BMI ≥ 29.4 (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20-0.86; P = .017) and presence of the aneurysm within the anterior circulation (OR 0.26, 95% CI 0.06-0.79; P = .016) were associated with a reduced likelihood of DCI. Severe WFNS (OR 2.56, 95% CI 1.20-5.46; P = .015) and modified Fisher scores (OR 2.59, 95% CI 1.06-7.34; P = .036), intracerebral hemorrhage (OR 2.72, 95% CI 1.27-5.86; P = .010), and increasing maximum velocity on TCD (Unit OR 1.19, 95% CI 1.10-1.30; P < .001) were associated with increased likelihood of DCI. BMI ≥ 29.4 was associated with reduced odds of delayed infarction (OR 0.19, 95% CI 0.03-0.73; P = .013). Predictors of delayed infarction were similar to those of DCI, as severe WFNS (OR 4.42, 95% CI 1.47-13.56; P = .009) and modified Fisher scores (OR NA [see text]; P = .036), intracerebral hemorrhage (OR 6.32, 95% CI 2.11-20.27; P = .001), and increasing maximum velocity on TCD (Unit OR 1.30, 95% CI 1.14-1.52; P < .001) were associated with increased likelihood of delayed infarction. The complete results of univariate analyses are presented in Table 2. TABLE 2. Univariate Logistic Regression Analysis Indicating Predictors of Delayed Cerebral Ischemia and Delayed Hypodensities Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  BMI, body mass index; DCI, delayed cerebral ischemia; TCD, transcranial Doppler; WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 1 unit increase in age and aneurysm size and every 10 unit increase in maximum velocity on TCD. bAs every patient with delayed cerebral hypodensities was diagnosed with delayed cerebral ischemia, DCI was not included in this univariate analysis. cAn OR could not be calculated as all patients with delayed hypodensities presented with a Modified Fisher score > 2. View Large TABLE 2. Univariate Logistic Regression Analysis Indicating Predictors of Delayed Cerebral Ischemia and Delayed Hypodensities Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  Variable  OR (95% CI)  P-Value  Delayed Cerebral Ischemia    Age  1.00 (0.97-1.02)a  .76  Female  1.73 (0.27-1.19)  .15  BMI ≥ 29.4  0.43 (0.20-0.86)  .017  Hypertension  0.89 (0.45-1.74)  .73  Smoker on Admission  0.97 (0.49-1.89)  .92  WFNS 4-5  2.56 (1.20-5.46)  .015  Modified Fisher 3-4  2.59 (1.06-7.34)  .036  Intracerebral Hemorrhage  2.72 (1.27-5.86)  .010  External Ventricular Drainage  1.51 (0.77-2.99)  .23  Aneurysm Size  1.06 (0.98-1.15)a  .16  Anterior Circulation  0.26 (0.06-0.79)  .016  Clipping  0.76 (0.31-1.71)  .51  Maximum Velocity on TCD  1.19 (1.10-1.30)a  <.001  Delayed Cerebral Infarctionb    Age  0.98 (0.94-1.02)a  .36  Female  2.21 (0.67-10.02)  .24  BMI ≥ 29.4  0.19 (0.03-0.73)  .013  Hypertension  0.53 (0.17-1.56)  .25  Smoker on Admission  1.82 (0.62-5.67)  .27  WFNS 4-5  4.42 (1.47-13.56)  .009  Modified Fisher 3-4  NAc  .005  Intracerebral Hemorrhage  6.32 (2.11-20.27)  .001  External Ventricular Drainage  2.90 (0.95-10.86)  .063  Aneurysm Size  1.03 (0.88-1.17)a  .68  Anterior Circulation  0.82 (0.12-3.25)  .80  Clipping  0.55 (0.08-2.12)  .42  Maximum Velocity on TCD  1.30 (1.14-1.52)a  <.001  BMI, body mass index; DCI, delayed cerebral ischemia; TCD, transcranial Doppler; WFNS, World Federation of Neurosurgical Societies. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 1 unit increase in age and aneurysm size and every 10 unit increase in maximum velocity on TCD. bAs every patient with delayed cerebral hypodensities was diagnosed with delayed cerebral ischemia, DCI was not included in this univariate analysis. cAn OR could not be calculated as all patients with delayed hypodensities presented with a Modified Fisher score > 2. View Large On multivariate stepwise analysis, BMI ≥ 29.4 remained associated with reduced likelihood of DCI (OR 0.42, 95% CI 0.18-0.92). Increasing maximum velocity on TCD was independently associated with an increased likelihood of DCI (Unit OR 1.19, 95% CI 1.09-1.30; P < .001). BMI ≥ 29.4 was also independently associated with reduced odds of delayed cerebral infarction (OR 0.13, 95% CI 0.02-0.61; P = .008). Intracerebral hemorrhage (OR 6.99, 95% CI 1.82-30.25; P = .005) and increasing maximum velocity on TCD (Unit OR 1.31, 95% CI 1.13-1.56; P < .001) were independently associated with increased odds of delayed infarction (Table 3). TABLE 3. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of DCI and Delayed Infraction Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 10 cm/s increase in maximum velocity on TCD. View Large TABLE 3. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of DCI and Delayed Infraction Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  Variable  OR (95% CI)  P-Value  C-Statistic  Delayed Cerebral Ischemia    BMI ≥ 29.4  0.42 (0.18-0.92)  .030    Maximum Velocity on TCD  1.19 (1.09-1.30)a  <.001  0.737  Delayed Cerebral Infarction    BMI ≥ 29.4  0.13 (0.02-0.61)  .008    Intracerebral Hemorrhage  6.99 (1.82-30.25)  .005    Maximum Velocity on TCD  1.31 (1.13-1.56)a  <.001  0.891  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. aUnit OR, indicating the increase in OR for every 10 cm/s increase in maximum velocity on TCD. View Large We also examined whether BMI was associated with poor functional outcome. On univariate analysis, BMI ≥ 29.4 was not associated with poor functional outcome (OR 0.74, 95% CI 0.36-1.50; P = .41). Both DCI (OR 3.65, 95% CI 1.77-7.66; P < .001) and delayed infarction (OR 4.76, 95% CI 1.61-15.09; P = .005), however, were associated with increased odds of poor functional outcome (Table 4). TABLE 4. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of Poor Functional Outcome (Modified Rankin Scale > 2) Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. View Large TABLE 4. Multivariate Stepwise Logistic Regression Analysis Indicating Predictors of Poor Functional Outcome (Modified Rankin Scale > 2) Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  Variable  OR (95% CI)  P-Value  BMI ≥ 29.4  0.74 (0.36-1.50)  .41  Delayed Cerebral Ischemia  3.65 (1.77-7.66)  <.001  Delayed Cerebral Infarction  4.76 (1.61-15.09)  .005  BMI, body mass index; TCD, transcranial Doppler. Bolded text indicates statistical significance. View Large Relationship of BMI to TCD Velocities and Incidence of Angiographic Vasospasm We then investigated whether an association was present between patient BMI and maximum velocity on TCD. On linear regression analysis, there was no relationship between BMI and maximum velocity on TCD (r2 = 0.001; Figure 2). There was also no difference in average maximum velocity between patients with BMI < 29.4 and those with BMI ≥ 29.4 (113.1 vs 105.1; P = .16). Angiographic vasospasm occurred in similar frequencies between patients with BMI < 29.4 and ≥ 29.4 (43.2% vs 39.7%; P = .68). FIGURE 2. View largeDownload slide Linear regression analysis of relationship of BMI to maximal velocity on TCD. The graph depicts maximal velocity on TCD as a function of patient BMI, with the blue line depicting the relationship determined by linear regression analysis. Shaded areas denote 95% CIs. BMI, body mass index; TCD, transcranial Doppler. FIGURE 2. View largeDownload slide Linear regression analysis of relationship of BMI to maximal velocity on TCD. The graph depicts maximal velocity on TCD as a function of patient BMI, with the blue line depicting the relationship determined by linear regression analysis. Shaded areas denote 95% CIs. BMI, body mass index; TCD, transcranial Doppler. DISCUSSION In the present study, we describe an association between increased BMI and reduced incidence of both DCI and subsequent delayed cerebral infarction after aSAH. These results suggest a mechanism through which increased BMI may contribute to improved functional outcome after aSAH.10,16 Relationship of BMI to Outcomes After Subarachnoid Hemorrhage While we observed a significant association between BMI and delayed ischemia, we did not observe an association of BMI with patient functional outcomes. The effect of BMI on outcomes after aSAH remains controversial, with conflicting results reported previously in the literature.9-16 A recent study suggests that the effect of BMI on outcomes after aSAH may depend on treatment modality, with increased BMI conferring a positive and negative effect in patients treated with coiling versus clipping, respectively.16 Obesity may increase the risks of surgery in general18 and intracranial surgery in particular.19 As such, a beneficial effect of BMI may be more likely to manifest only in patients treated with endovascular coiling, and possibly in patients at higher risk of DCI. Moreover, previous large-scale studies have found differing of BMI on patient outcomes when stratified by the degree of obesity, with potential benefit observed in patients with mild as opposed to morbid obesity.9 To better understand how BMI influences the prognosis of patients after aneurysm rupture, additional, more quantitative studies investigating how BMI affects the incidence of different forms of both neurological and nonneurological morbidity are needed. Mechanism of Effect of BMI on Incidence of Delayed Infarcts The mechanism by which increased BMI may be protective against delayed ischemia is not immediately clear. We did not observe an association of BMI with maximal velocities measured on serial TCD examinations or with the incidence of angiographic vasospasm among patients who underwent vascular imaging after aneurysm treatment, though it is known that the correlation between the detection of vasospasm by TCD or angiography and the occurrence of cerebral ischemia (defined as either DCI or cerebral infarction) is suboptimal.20 It has been proposed that vasospasm alone is not sufficient to produce DCI,21 the pathophysiology of which is complex and multifactorial.4 It is possible that obesity confers resistance to neuronal dysfunction in the setting of ischemia. For example, leptin, a hormone produced by adipocytes involved in the regulation of satiety, has been shown in vitro to have protective effects against cerebral ischemia.22-24 Of note, however, obesity has been associated with leptin resistance within the central nervous system.25 Obesity has also been associated with remodeling of the cerebral vasculature, specifically intimal and medial thickening secondary to impaired nitric oxide-mediated signaling pathways.26 Interestingly, DCI may result in part from impaired nitric oxide-mediated vasodilatation, leading to pial vessel vasoconstriction in response to hemorrhage on the cortical surface.4 It is possible that reduced dependence on nitric oxide-dependent pathways confers resistance to DCI. On the other hand, baseline impairment of compensatory vasodilation could alternatively predispose to neurological deterioration in response to cerebral ischemia. Further investigation into the cellular and molecular effects of increased BMI, and how they may translate into cerebral protection in the setting of aSAH is warranted. Relationship of Intracerebral Hemorrhage to Incidence of Delayed Infarction We also observed an independent association between intracerebral hemorrhage on presentation with aSAH and the incidence of delayed cerebral infarction. Previous studies have described an association of intracerebral hemorrhage with both DCI27-28 and poor functional outcome29 after aSAH. Our results provide further evidence of the prognostic significance of intraparenchymal hemorrhage resulting from aneurysmal rupture. Limitations Our study is limited by the relatively small sample size, in particular the small number of delayed infarctions. Larger studies will be needed to confirm our results. An additional limitation is our retrospective and single-center methodology. Specifically, though each patient within our cohort underwent at least 1 immediate postprocedural and delayed CT scan, images were nevertheless obtained when warranted by clinical circumstances and at the discretion of the treating team. As such, it is possible that clinically silent infarctions were missed, which could explain the reduced incidence of delayed infarction observed in our study when compared to previous cohorts treated at our institution.20,30 Moreover, CT imaging is not the most sensitive modality to detect cerebral infarction. While we reviewed all available CT scans, including those obtained after discharge, to support the determination of infarction, it is possible that some patients were incorrectly categorized as suffering infarction or that some infarctions were missed due to the limitations of CT imaging. Adjunct imaging techniques with increased sensitivity for ischemia, such as MRI and CT perfusion, were obtained in only a minority of patients, and thus future studies may benefit from the scheduled use of these techniques to assess for infarction. Infarcts were considered to be delayed if they were not present on head CT imaging obtained within 3 d of surgical intervention. Though images first demonstrating evidence of delayed infarction were obtained at an average of 9.7 d after initial surgery, it is possible that in certain cases infarcts occurring in the perioperative period were simply not detected until later in the patient's clinical course due to the limited sensitivity and inconsistent timing of CT imaging. Again, future studies utilizing the scheduled use of more sensitive imaging techniques both during and after the perioperative period may be needed to confirm the association of increased BMI and delayed infarction. Maximal velocity on TCD in any vessel was recorded for each patient. While increasing velocity was well correlated with both angiographic vasospasm and the incidence of delayed infarction, lower velocities may nevertheless represent significant vasospasm in certain areas of the Circle of Willis, particularly the posterior circulation. To better understand the mechanism by which BMI may lead to DCI and subsequent infarction, a more in-depth analysis of TCDs with cut-offs specific to different arterial locations may be needed. Finally, the variables included in our multivariate analysis are almost certainly inter-related to a certain degree, and thus multicollinearity may have influenced the observed association of individual predictors to outcomes of interest. Our findings require confirmation in future studies. CONCLUSION We describe an association with increased BMI and delayed neurological deterioration and subsequent cerebral infarction after aSAH. 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Journal

NeurosurgeryOxford University Press

Published: Apr 4, 2018

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