Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study

The purpose of this study is to establish the diagnostic sensitivity of Endothelin-1 for risk stratification and screening of clinical vasospasm after subarachnoid hemorrhage. This is a multicentre, observational study, correlating daily blood Endothelin-1 with clinical variables. Binary logistic regression used to examine if Endothelin-1 levels could be used to predict clinical vasospasm. Bivariate modelling used to explore associations between patient characteristics and vasospasm. A Receiver Operating Curve used to explore cut-off values for Endothelin-1. Sensitivity and specificity was used to validate the cut-point found in the pilot study. A total of 96 patients were enrolled over two years. Median Endothelin-1 was higher for patients who experienced clinical vasospasm except for day-5, where median endothelin for patients without vasospasm was higher (3.6 IQR = 5.3), compared to patients with vasospasm (3.3 IQR = 8.5) although differences were not significant. The Receiver Operating Curve analysis confirmed that day-5 Endothelin-1 was not a good indicator of vasospasm, with an area under the curve of 0.506 (95% CI: 0.350-0.663, p = 0.938). The levels of Endothelin-1 in blood do not discriminate patients who may develop symptomatic vasospasm. The high variability in Endothelin-1 levels, aligns with the pathophysiological variability of most biomarkers, decreasing their ability to predict a clinical event.

Antiplatelet therapy and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

OBJECTIVE Delayed cerebral ischemia (DCI) is a potentially preventable cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). The authors performed a meta-analysis to assess the effect of antiplatelet therapy (APT) on DCI in patients with aSAH. METHODS A systematic review of the PubMed and MEDLINE databases was performed. Study inclusion criteria were 1) ≥ 5 aSAH patients; 2) direct comparison between aSAH management with APT and without APT; and 3) reporting of DCI, angiographic, or symptomatic vasospasm rates for patients treated with versus without APT. The primary efficacy outcome was DCI. The outcomes of the APT versus no-APT cohorts were compared. Bias was assessed using the Downs and Black checklist. RESULTS The overall cohort comprised 2039 patients from 15 studies. DCI occurred less commonly in the APT compared with the no-APT cohort (pooled = 15.9% vs 28.6%; OR 0.47, p < 0.01). Angiographic (pooled = 51.6% vs 68.7%; OR 0.46, p < 0.01) and symptomatic (pooled = 23.6% vs 37.7%; OR 0.51, p = 0.01) vasospasm rates were lower in the APT cohort. In-hospital mortality (pooled = 1.7% vs 4.1%; OR 0.53, p = 0.01) and functional dependence (pooled = 21.0% vs 35.7%; OR 0.53, p < 0.01) rates were also lower in the APT cohort. Bleeding event rates were comparable between the two cohorts. Subgroup analysis of cilostazol monotherapy compared with no APT demonstrated a lower DCI rate in the cilostazol cohort (pooled = 10.6% vs 28.1%; OR 0.31, p < 0.01). Subgroup analysis of surgically treated aneurysms demonstrated a lower DCI rate for the APT cohort (pooled = 18.4% vs 33.9%; OR 0.43, p = 0.02). CONCLUSIONS APT is associated with improved outcomes in aSAH without an increased risk of bleeding events, particularly in patients who underwent surgical aneurysm repair and those treated with cilostazol. Although study heterogeneity is the most significant limitation of the analysis, the findings suggest that APT is worth exploring in patients with aSAH, particularly in a randomized controlled trial setting.

Effect of stress-induced hyperglycemia after non-traumatic non-aneurysmal subarachnoid hemorrhage on clinical complications and functional outcomes

Background Despite having an overall benign course, non-traumatic non-aneurysmal subarachnoid hemorrhage (naSAH) is still accompanied by a risk of clinical complications and poor outcomes. Risk factors and mechanisms of complications and poor outcomes after naSAH remain unknown. Our aim was to explore the effect of stress-induced hyperglycemia (SIH) on complication rates and functional outcomes in naSAH patients. Methods We retrospectively reviewed patients with naSAH admitted to our institution between 2013 and 2018. SIH was identified according to previous criterion. Symptomatic vasospasm, delayed cerebral infarction, and hydrocephalus were identified as main complications. Outcomes were reviewed using a modified Rankin Scale (mRS) at discharge, 3 months, and 12 months. A statistical analysis of clinical, radiological, and laboratory risk factors of complications and outcomes was conducted. Results 244 naSAH patients were incorporated in the cohort with 74 (30.3%) SIH. After adjusting for age, gender, hypertension, Hunt and Hess (HH) grade, modified Fisher Scale (mFS), intraventricular hemorrhage (IVH), and subarachnoid blood distribution, SIH was significantly associated with symptomatic vasospasm (P < 0.001, 12.176 [4.904–30.231]), delayed cerebral infarction (P < 0.001, 12.434 [3.850-40.161]), hydrocephalus (P = 0.008, 5.771 [1.570-21.222]), and poor outcome at 12 months (P = 0.006, 5.506 [1.632–18.581]), whereas the correlation between SIH and poor outcome at discharge (P = 0.064, 2.409 [0.951-6.100]) or 3 months (P = 0.110, 2.029 [0.852–4.833]) was not significant. Incorporation of SIH increased the area under curve (AUC) of ROC in the combined model for predicting symptomatic vasospasm (P = 0.002), delayed cerebral infarction (P = 0.024), hydrocephalus (P = 0.037), and 12-month poor outcome (P = 0.087). Conclusions SIH is a significant and independent risk factor for symptomatic vasospasm, delayed cerebral infarction, hydrocephalus, and long-term poor outcome in naSAH patients. Identifying SIH early after naSAH is important for decision-making and treatment planning.

Abstract MP12: Drivers of Rescue Therapy Efficacy for Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: A Propensity-Score Matched Analysis With Machine Learning

Introduction: One of the foremost challenges in subarachnoid hemorrhage (SAH) management is understanding which patient characteristics and treatment decisions lead to good outcomes. This study uses novel game theory-based methods in explainable machine learning (ML) and propensity-score matching to elucidate the clinical factors driving outcomes following rescue therapy for post-SAH vasospasm. Methods: Data for patients with post-SAH angiographic or symptomatic vasospasm were obtained from six clinical trials and observational studies in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and 3-month Glasgow Outcome Scale (GOS) scores. Shapley Additive Explanation (SHAP) values were calculated to quantify feature importance and interaction effects. Variables with high SHAP importance in predicting rescue therapy were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. Results: A total of 1,532 patients were included. SAH characteristics and neurological sequelae, but not admission neurological scores, heavily influenced the probability of receiving rescue therapy. Comparing feature importances showed cerebral ischemia/infarction was invariably linked to poor outcome, while other important predictors of outcome varied by rescue type. Higher blood pressures and fewer postoperative days until vasospasm treatment were more important for predicting worse outcome following interventional rescue, while high admission WFNS grade and pneumonia were important predictors of worse outcome for non-interventional rescue. Finally, in a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS of 4-5 (odds ratio: 1.63; 95%CI 1.22-2.17; p=0.001). Conclusion: Rescue therapy for vasospasm was associated with good functional outcomes. Future randomized trials focusing on preventative or therapeutic interventions may be able to demonstrate improvements in clinical outcomes. Insights from these models may help improve patient selection criteria and trial designs for rescue therapy.

Abstract P405: A Time-Series Forecast Model to Assess Vital Sign Waveform Variability Prior to Vasospasm

Introduction: Symptomatic vasospasm (SV) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and can lead to cerebral infarction. Changes in vital trends, such as heart rate (HR) and mean arterial blood pressure (MAP), have been associated with SV in aSAH. Real-time assessment of instantaneous vital sign waveform data could improve detection of vital sign variability associated with vasospasm. However, no model using instantaneous waveform data exists to predict SV. We hypothesize that autoregressive integrated moving average (ARIMA) analysis, a time-series forecast model, is a useful approach to assess the variability of vital sign waveforms associated with SV. Methods: In this small case-control study, vital signs of patients admitted to the neuroICU with aSAH were obtained using a software-based analytics platform, Sickbay. HR and MAP from 15 aSAH patients were continuously obtained from ECG and arterial line waveforms. Ten patients developed neurologic deficits attributed to angiographically-confirmed SV (Det). Five controls (Con) without SV were matched based on age. 3 Det and 3 Con were randomly selected for further analysis. For Det, waveforms were analyzed at 5-second intervals for 48 hours prior to clinical deterioration. For Con, waveforms were analyzed at a random 48-hour interval. Results: Visually, MAP and not HR was more variable in Det than in Con patients (Figure). The ARIMA model plotted the forecasted-fit for each delta-variable waveform. The MAP confidence interval margins were significantly larger for Det patients compared to the Con patient. This trend was consistent across all other patients. Conclusion: ARIMA is a useful tool to assess HR and MAP waveform variations prior to SV in aSAH. Larger studies are required to solidify this concept and further explore the combination of data analytics platform and ARIMA to predict neurological deterioration in SV.

Serum glucose as an important predictor of delayed cerebral ischemia in angiogram-negative subarachnoid hemorrhage

Background Despite benign overall course, angiogram-negative subarachnoid hemorrhage (AN-SAH) still companies with risk of delayed cerebral ischemia (DCI). Serum glucose was previously found to be related to DCI occurrence in aneurysmal subarachnoid hemorrhage (aSAH), but this has not been confirmed in AN-SAH. The aim of this study was to clarify the significance of serum glucose in DCI prediction in AN-SAH patients. Methods We included patients with AN-SAH admitted to our hospital between January 2013 and December 2018. According to different bleeding patterns, patients were divided into perimesencephalic AN-SAH (PAN-SAH) and non-perimesencephalic AN-SAH (NPAH-SAH) patients. DCI was defined as symptomatic vasospasm or/and delayed cerebral infarction. A statistical analysis of the clinical, radiological, and laboratory risk factors of DCI was conducted. Logistic regression analysis was performed to identify the independent predictors of DCI. Results A total of 244 AN-SAH patients (mean age 55.7 years, 55.7% men) were included with 164 (67.2%) PAN-SAH patients and 80 (32.8%) NPAN-SAH patients. There were significant correlations between high DCI incidence and high serum glucose levels in the first five days after admission in both PAN-SAH patients and NPAN-SAH patients (p < 0.05). High admission serum glucose was significantly related to higher World Federation of Neurosurgeons Scale (WFNS) (p < 0.05). Multivariate logistic regression analysis showed that admission serum glucose (p = 0.001, OR 1.705, 95% CI 1.232–2.360) and WFNS (p = 0.008, OR 2.889, 95% CI 1.322–6.311) were both significant and independent predictors for DCI occurrence in PAN-SAH patients. Admission serum glucose (p = 0.016, OR 2.307, 95% CI 1.167–4.562), standard deviation (SD) of the serum glucose in the first three days after admission (p = 0.049, OR 5.684, 95% CI 1.006–32.114) and modified Fisher scale (mFS) (p = 0.033, OR 1.859, 95% CI 1.051–3.288) were significant and independent predictors for DCI occurrence in NPAN-SAH patients. Conclusions Serum glucose is an early biomarker to predict DCI risk in both PAN-SAH and NPAN-SAH patients, which has an important value in guiding intensive care in AN-SAH patients.

Cerebral Vasospasm after Posterior Fossa Tumor Surgery: A Case Report and Literature Review

<b><i>Introduction:</i></b> This report presents an unusual case of symptomatic vasospasm following resection of posterior fossa tumor in a 9-year-old female patient. To the best of our knowledge, only 6 pediatric cases of vasospasms as a complication of brain tumor surgery have been reported in the literature previously. <b><i>Case Presentation:</i></b> After an uneventful 12 days postoperatively, the patient suddenly presented with acute neurological deterioration on the 13th day and MR angiography showed bilateral narrowing of the supraclinoid segments of the internal carotid artery and the proximal parts of the A1 and M1 segments. Hypervolemia and vasospasm treatments were administered, and the patient exhibited no neurological deficit at the time of discharge, confirmed via normal MRI. <b><i>Conclusion:</i></b> Early diagnosis and intervention in case of suspected symptomatic cerebral vasospasm after pediatric posterior fossa tumor surgery are essential in order to achieve favorable outcomes.