Aneurysmal Subarachnoid Hemorrhage Patients Research Articles

Pre-operative prognostic nutrition index and post-operative pneumonia in aneurysmal subarachnoid hemorrhage patients.

Post-operative pneumonia (POP), a common complication, may be associated with prolonged hospitalization and long-term mortality in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to explore the association between pre-operative prognostic nutrition index (PNI) and POP in aSAH patients. A total of 280 aSAH patients were enrolled from Nanjing Drum Tower Hospital. PNI was calculated as follows: [10 × albumin(gr/dl)] + [0.005 × absolute pre-operative lymphocyte count (per mm3)]. We utilized multivariate analyses, restricted cubic spline, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to elucidate the role of PNI in POP. Pre-operative PNI levels in the POP group were higher, compared with the non-POP group (41.0 [39.0, 45.4] vs. 44.4 [40.5, 47.3], P = 0.001). When we included PNI as a categorical variable in the multivariate analysis, the levels of PNI were associated with POP (odds ratio, 0.433; 95% confidence interval, 0.253-0.743; P=0.002). In addition, when we included PNI as a continuous variable in the multivariate analysis, the PNI levels were also associated with POP (odds ratio, 0.942; 95% confidence interval, 0.892-0.994; P = 0.028). The level of albumin was also a predictor of the occurrence of POP, with a lower diagnostic power than PNI [AUC: 0.611 (95% confidence interval, 0.549-0.682; P = 0.001) for PNI vs. 0.584 (95% confidence interval, 0.517-0.650; P = 0.017) for albumin]. Multivariable-adjusted spline regression indicated a linear dose-response association between PNI and POP in aSAH participants (P for linearity = 0.027; P for non-linearity = 0.130). Reclassification assessed by IDI and NRI was significantly improved with the addition of PNI to the conventional model of POP in aSAH patients (NRI: 0.322 [0.089-0.555], P = 0.007; IDI: 0.016 [0.001-0.031], P = 0.040). The lower levels of pre-operative PNI may be associated with the higher incidence of POP in aSAH patients. Neurosurgeons are supposed to pay more attention to pre-operative nutrition status in aSAH patients.

Impact of Circle of Willis Anatomical Variations on Outcomes in Aneurysmal Subarachnoid Hemorrhage (P7-5.027)

<h3>Objective:</h3> We sought to determine the association between circle of Willis (CoW) anatomical variations and outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. <h3>Background:</h3> The impact of CoW anatomical variations on vasospasm risk and functional outcome in patients with aSAH is poorly understood. <h3>Design/Methods:</h3> We performed a retrospective study on a single center cohort of patients with aSAH admitted to an academic center between 2015 and 2022. After reviewing imaging, we classified CoW variants into 4 categories: 1) incomplete anterior segments if either proximal anterior cerebral or anterior communicating arteries were absent or hypoplastic (with a 1mm diameter cutoff), 2) incomplete posterior segments if posterior communicating or proximal posterior cerebral arteries were absent or hypoplastic; 3) complete CoW; 4) others. Outcomes include vasospasm based on transcranial Doppler (TCD) criteria and poor functional outcome defined as modified Rankin Scale 4–6 at 3 months post discharge. Binary logistic regression analysis was used to test the association of each CoW variant with outcomes. <h3>Results:</h3> We included 178 patients with aSAH (mean age 55.9 years [SD 13.6], 56% female). Eighty percent of patients had incomplete CoW and they were older than those with complete CoW (mean age 57.4 [SD12.7] vs 49.9 [15.4]; p=0.003). Incomplete posterior segments were seen in 73% of patients. The presence of incomplete anterior segments was more common in females (11% vs 1%; p=0.01) and it was associated with vasospasm (OR 2.39, 95% CI 1.02–5.63; p=0.042), but not with poor functional outcome (p=0.89). There was no association between incomplete posterior segments and vasospasm risk (p=0.29) or poor functional outcome (p=0.93). <h3>Conclusions:</h3> Anatomical variations of the CoW may affect TCD findings but did not appear to be associated with poor outcomes. Larger prospective studies are needed to explore clinical significance of CoW variants in aSAH patients. <b>Disclosure:</b> Scott Moody has nothing to disclose. Mr. Pham has nothing to disclose. Mr. Ozcan has nothing to disclose. Miss Haripottawekul has nothing to disclose. Dr. Subramaniam has nothing to disclose. Dr. Reznik has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Morrison Mahoney. The institution of Dr. Reznik has received research support from NIDUS. The institution of Dr. Furie has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen/BMS. The institution of Dr. Furie has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ACTICOR. Dr. Furie has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for BMJ/JNNP. The institution of Dr. Furie has received research support from NINDS. Dr. Yaghi has nothing to disclose. Dr. Mahta has nothing to disclose.

A Machine Learning Tool to Predict Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage (P13-7.003)

<h3>Objective:</h3> To utilize a machine learning and deep learning approach to derive a clinically applicable tool to predict the development of vasospasm in aneurysmal subarachnoid hemorrhage (aSAH) patients. <h3>Background:</h3> Cerebral vasospasm, is a common undesired and feared consequence of aSAH occurring in up to 70% of patients. Cerebral vasospasm may present anywhere from 24 hours to 7–10 days post SAH and is difficult to predict. Several radiological and clinical features have been proposed as potential predictors of cerebral vasospasm in previous models including, however, these predictors have not successfully been standardized and weighted through an artificial intelligence algorithm. While risk factors for vasospasm is known, there is also no validated single tool in practice that accounts for the broad diversity in indicators that may be predictive of cerebral vasospasm. <h3>Design/Methods:</h3> We retrospectively analyzed aneurysmal SAH patients who were admitted to the Carle Foundation Hospital in the Critical Care Unit from January 2016 to December 2021. Total of 52 patients met study criteria, out of which 23 (44%) patients were identified to have vasospasm through diagnostic imaging modalities. Clinical, radiological, and laboratory data were collected and analyzed through various feature selection and artificial intelligence models. Models were validated using 10-fold Cross-Validation. <h3>Results:</h3> We included Transcranial Doppler data from 14 days post aSAH, as well as Fisher Score, Hunt Hess Score, diameter of aneurysm, lymphocyte/monocyte/WBC counts, motor component from Glasgow Coma Scale, and home medication for anticoagulants in our model. Models including Logistic Model Trees, Logistic Regression, AdaBoost, LogitBoost, Hoeffding Tree, and Multilayer Perceptron (MP) were trained, with MP performing with the highest ROC AUC of 0.829, with a TP Rate of 73%, FP Rate of 28.5%, Precision of 73%, and F-Measure of 73%. <h3>Conclusions:</h3> A framework for predicting cerebral vasospasm after aSAH through deep learning is created with ROC AUC of 0.829. <b>Disclosure:</b> Mr. Patel has nothing to disclose. Mr. Pandya has nothing to disclose. Ms. Mann has nothing to disclose.

Fingolimod Reduces Cardiac Macrophage Infiltration after Experimental Subarachnoid Hemorrhage (P13-7.002)

<h3>Objective:</h3> We investigated macrophage infiltration into the rat heart after experimental subarachnoid hemorrhage (SAH) and whether this is attenuated by treatment with the immunomodulatory agent fingolimod. <h3>Background:</h3> Upwards of 70% of aneurysmal SAH patients suffer from cardiac dysfunction despite not having any primary cardiac disease. It is unclear if this is related to systemic inflammation or autonomic dysregulation. Previously, our lab showed that early elevations in serum white blood cells can predict cardiac injury in SAH patients. <h3>Design/Methods:</h3> SAH was induced in rats using the endovascular perforation model and compared to sham controls (n=4 per group). Additional sham and SAH animals were treated with fingolimod, given intraperitoneally 3 hours after the procedure (0.5 mg/kg, single dose). Cardiac tissue was harvested two days postoperatively and stained for the macrophage marker Iba-1 at both the apex and base of the heart. Blinded analysis was performed to Iba-1+ cell count, area, size, and circularity. Significance was determined by one-way ANOVA with Tukey’s multiple comparisons test. <h3>Results:</h3> The number of Iba-1+ cells was lower in the sham and SAH-fingolimod treated groups than in the SAH-vehicle group (SAH-vehicle: 40.87±2.43 cells/hpf; sham: 11.8±0.71 cells/hpf, p&lt;0.0001; SAH-fingolimod 7.8±0.37 cells/hpf, p&lt;0.0001). There was no difference in average Iba-1+ cell size across groups (p&gt;0.05). Attenuation in the number of Iba-1⁺ cells in the heart was observed at both the apex and base; however, the effect of fingolimod was more pronounced at the apex. Additionally, Iba-1⁺ cells at the apex displayed increased circularity compared to shams (p=0.0232), which may be associated with a more amoeboid, activated state. <h3>Conclusions:</h3> Following SAH, there are increased macrophages in the heart compared to shams, indicating increased cardiac inflammation. Treatment with fingolimod reduces macrophage infiltration and may lead to improved outcomes. Additional studies are needed to investigate if immunomodulation reduces SAH-associated cardiac dysfunction. <b>Disclosure:</b> Mr. Geraghty has received publishing royalties from a publication relating to health care. Mr. Saini has nothing to disclose. Dr. Testai has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Swanson Martin &amp; Bell, LLP. Dr. Testai has received publishing royalties from a publication relating to health care.

Prediction of delayed cerebral ischemia after cerebral aneurysm rupture using explainable machine learning approach.

Aneurysmal subarachnoid hemorrhage results in significant mortality and disability, which is worsened by the development of delayed cerebral ischemia. Tests to identify patients with delayed cerebral ischemia prospectively are of high interest. We created a machine learning system based on clinical variables to predict delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients. We also determined which variables have the most impact on delayed cerebral ischemia prediction using SHapley Additive exPlanations method. 500 aneurysmal subarachnoid hemorrhage patients were identified and 369 met inclusion criteria: 70 patients developed delayed cerebral ischemia (delayed cerebral ischemia+) and 299 did not (delayed cerebral ischemia-). The algorithm was trained based upon age, sex, hypertension (HTN), diabetes, hyperlipidemia, congestive heart failure, coronary artery disease, smoking history, family history of aneurysm, Fisher Grade, Hunt and Hess score, and external ventricular drain placement. Random Forest was selected for this project, and prediction outcome of the algorithm was delayed cerebral ischemia+. SHapley Additive exPlanations was used to visualize each feature's contribution to the model prediction. The Random Forest machine learning algorithm predicted delayed cerebral ischemia: accuracy 80.65% (95% CI: 72.62-88.68), area under the curve 0.780 (95% CI: 0.696-0.864), sensitivity 12.5% (95% CI: -3.7 to 28.7), specificity 94.81% (95% CI: 89.85-99.77), PPV 33.3% (95% CI: -4.39 to 71.05), and NPV 84.1% (95% CI: 76.38-91.82). SHapley Additive exPlanations value demonstrated Age, external ventricular drain placement, Fisher Grade, and Hunt and Hess score, and HTN had the highest predictive values for delayed cerebral ischemia. Lower age, absence of hypertension, higher Hunt and Hess score, higher Fisher Grade, and external ventricular drain placement increased risk of delayed cerebral ischemia. Machine learning models based upon clinical variables predict delayed cerebral ischemia with high specificity and good accuracy.

A visualized MAC nomogram online predicts the risk of three-month mortality in Chinese elderly aneurysmal subarachnoid hemorrhage patients undergoing endovascular coiling.

Aneurysmal subarachnoid hemorrhage (aSAH) is an aggressive disease with higher mortality rate in the elderly population. Unfortunately, the previous models for predicting clinical prognosis are still not accurate enough. Therefore, we aimed to construct and validate a visualized nomogram model to predict online the 3-month mortality in elderly aSAH patients undergoing endovascular coiling. We conducted a retrospective analysis of 209 elderly aSAH patients at People's Hospital of Hunan Province, China. A nomogram was developed based on multivariate logistic regression and forward stepwise regression analysis, then validated using the bootstrap validation method (n = 1000). In addition, the performance of the nomogram was evaluated by various indicators to prove its clinical value. Morbid pupillary reflex, age, and using a breathing machine were independent predictors of 3-month mortality. The AUC of the nomogram was 0.901 (95% CI: 0.853-0.950), and the Hosmer-Lemeshow goodness-of-fit test showed good calibration of the nomogram (p = 0.4328). Besides, the bootstrap validation method internally validated the nomogram with an area under the curve of the receiver operator characteristic (AUROC) of 0.896 (95% CI: 0.846-0.945). Decision curve analysis (DCA) and clinical impact curve (CIC) indicated the nomogram's excellent clinical utility and applicability. An easily applied visualized nomogram model named MAC (morbid pupillary reflex-age-breathing machine) based on three accessible factors has been successfully developed. The MAC nomogram is an accurate and complementary tool to support individualized decision-making and emphasizes that patients with higher risk of mortality may require closer monitoring. Furthermore, a web-based online version of the risk calculator would greatly contribute to the spread of the model in this field.

Elevated Serum NOX2 Levels Contribute to Delayed Cerebral Ischemia and a Poor Prognosis After Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

NADPH oxidase 2 (NOX2) is highly expressed in injured brain tissues. We determined serum NOX2 levels of aneurysmal subarachnoid hemorrhage (aSAH) patients and further investigated correlation of serum NOX2 levels with disease severity, delayed cerebral ischemia (DCI) plus prognosis after aSAH. Serum NOX2 levels were measured in 123 aSAH patients and 123 healthy controls. World Federation of Neurological Surgeons scale (WFNS) score and modified Fisher (mFisher) score were utilized to assess disease severity. Modified Rankin scale (mRS) score was used to evaluate the clinical prognosis at 90 days after aSAH. Relations of serum NOX2 levels to DCI and 90-day poor prognosis (mRS score of 3-6) were analyzed using multivariate analysis. Receiver operating characteristic curve (ROC) was built to evaluate the prognostic predictive capability. Serum NOX2 levels in aSAH patients, compared with healthy controls, were significantly increased, and were independently correlated with WFNS score, mFisher score and post-stroke 90-day mRS score. Patients with poor prognosis or DCI had significantly higher serum NOX2 levels than other remainders, and serum NOX2 levels independently predicted 90-day poor prognosis and DCI. Serum NOX2 had high prognosis and DCI predictive abilities, and their areas under ROC curve were similar to those of WFNS score and mFisher score. Serum NOX2 levels are significantly associated with hemorrhage severity, poor 90-day prognosis and DCI in aSAH patients. Hence, complement NOX2 may serve as a potential prognostic biomarker after aSAH.

104 A Safety and Efficacy Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. Secondary mechanisms of injury can aggravate the high negative impact. Cerebral vasospasm (CV) is one of the most relevant causes of this secondary injury. To improve the current treatment options, NicaPlant® was developed. METHODS: The trial was performed as an international randomized, controlled, single-blinded multicenter study. 40 Patients with WFNS grade 3 and 4 SAH undergoing surgical repair of their ruptured aneurysm were randomized to receive ten pellets of NicaPlant® (40 mg) plus standard of care or standard of care alone. The implants were administered immediately following clip ligation of the ruptured aneurysm in proximity to all the exposed cerebral blood vessels. The primary endpoint was the incidence of moderate to severe CV (day 8 ± 1). A blinded independent outcome accessor analyzed all imaging data. RESULTS: In the implant group, 20% (4/20) of patients reached the primary endpoint, compared to 58% (11/19) of patients in the control group (p = 0.024). Including mild CV, 75% of all patients in the control group developed CV compared to 30% in the implant group (p = 0.0129). 32% (6/19) of the patients in the control group developed new cerebral infarction, compared to 10% (2/20) in the implant group (p = 0.1273). Endovascular rescue therapy was performed in 10% of the patients in the implant group compared to 58% in the control group (p = 0.002). 4 subjects (20%) in the control group experienced Treatment-emergent adverse events (TEAE), compared with none in the active group. CONCLUSIONS: In this prospective randomized multicenter Phase 2b trial, we could demonstrate the safety and efficacy of NicaPlant® implants in preventing CV in patients with SAH.

Elevated HMGB1 and sRAGE levels in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients

BackgroundNeuroinflammation after aneurysmal subarachnoid hemorrhage (aSAH) leads to poor outcome of patients. High mobility group box 1 (HMGB1) contributes to inflammation through binding to receptors for advanced glycation end-products (RAGE) in various diseases. We aimed to determine the production of these two factors after aSAH and their relationship with clinical features. MethodsHMGB1 and soluble RAGE (sRAGE) levels in cerebrospinal fluid (CSF) of aSAH patients and controls were measured, and their temporal courses were observed. The correlation between early concentrations (days 1-3) and clinical symptoms assessed by disease severity scores, neuroinflammation estimated by CSF IL-6 levels, as well as prognosis evidenced by delayed cerebral ischemia (DCI) and 6-month adverse outcome was investigated. Finally, combined analysis of early levels for predicting prognosis was confirmed. ResultsCSF HMGB1 and sRAGE levels were higher in aSAH patients than in controls (P < 0.05), and the levels decreased from higher early to lower over time. Their early concentrations were positively associated with disease severity scores, IL-6 levels, DCI and 6-month poor outcome (P < 0.05). HMGB1 ≥ 6045.5 pg/ml (OR = 14.291, P = 0.046) and sRAGE ≥ 572.0 pg/ml (OR = 13.988, P = 0.043) emerged as independent predictors for DCI, while HMGB1 ≥ 5163.2 pg/ml (OR = 7.483, P = 0.043) and sRAGE ≥ 537.3 pg/ml (OR = 12.653, P = 0.042) were predictors for 6-month poor outcome. Combined analysis of them improved predictive values of adverse prognosis. ConclusionCSF HMGB1 and sRAGE levels of aSAH patients were increased early and then varied dynamically, which might act as potential biomarkers for poor outcome, especially when co-analyzed.

Spreading depolarization and angiographic spasm are separate mediators of delayed infarcts.

In DISCHARGE-1, a recent Phase III diagnostic trial in aneurysmal subarachnoid haemorrhage patients, spreading depolarization variables were found to be an independent real-time biomarker of delayed cerebral ischaemia. We here investigated based on prospectively collected data from DISCHARGE-1 whether delayed infarcts in the anterior, middle, or posterior cerebral artery territories correlate with (i) extravascular blood volumes; (ii) predefined spreading depolarization variables, or proximal vasospasm assessed by either (iii) digital subtraction angiography or (iv) transcranial Doppler-sonography; and whether spreading depolarizations and/or vasospasm are mediators between extravascular blood and delayed infarcts. Relationships between variable groups were analysed using Spearman correlations in 136 patients. Thereafter, principal component analyses were performed for each variable group. Obtained components were included in path models with a priori defined structure. In the first path model, we only included spreading depolarization variables, as our primary interest was to investigate spreading depolarizations. Standardised path coefficients were 0.22 for the path from extravascular bloodcomponent to depolarizationcomponent (P = 0.010); and 0.44 for the path from depolarizationcomponent to the first principal component of delayed infarct volume (P < 0.001); but only 0.07 for the direct path from bloodcomponent to delayed infarctcomponent (P = 0.36). Thus, the role of spreading depolarizations as a mediator between blood and delayed infarcts was confirmed. In the principal component analysis of extravascular blood volume, intraventricular haemorrhage was not represented in the first component. Therefore, based on the correlation analyses, we also constructed another path model with bloodcomponent without intraventricular haemorrhage as first and intraventricular haemorrhage as second extrinsic variable. We found two paths, one from (subarachnoid) bloodcomponent to delayed infarctcomponent with depolarizationcomponent as mediator (path coefficients from bloodcomponent to depolarizationcomponent = 0.23, P = 0.03; path coefficients from depolarizationcomponent to delayed infarctcomponent = 0.29, P = 0.002), and one from intraventricular haemorrhage to delayed infarctcomponent with angiographic vasospasmcomponent as mediator variable (path coefficients from intraventricular haemorrhage to vasospasmcomponent = 0.24, P = 0.03; path coefficients from vasospasmcomponent to delayed infarctcomponent = 0.35, P < 0.001). Human autopsy studies shaped the hypothesis that blood clots on the cortex surface suffice to cause delayed infarcts beneath the clots. Experimentally, clot-released factors induce cortical spreading depolarizations that trigger (i) neuronal cytotoxic oedema and (ii) spreading ischaemia. The statistical mediator role of spreading depolarization variables between subarachnoid blood volume and delayed infarct volume supports this pathogenetic concept. We did not find that angiographic vasospasm triggers spreading depolarizations, but angiographic vasospasm contributed to delayed infarct volume. This could possibly result from enhancement of spreading depolarization-induced spreading ischaemia by reduced upstream blood supply.

Racial differences in time to blood pressure control of aneurysmal subarachnoid hemorrhage patients: A single-institution study.

Aneurysmal subarachnoid hemorrhage occurs in approximately 30,000 patients annually in the United States. Uncontrolled blood pressure is a major risk factor for aneurysmal subarachnoid hemorrhage. Clinical guidelines recommend maintaining blood pressure control until definitive aneurysm securement occurs. It is unknown whether racial differences exist regarding blood pressure control and outcomes (HLOS, discharge disposition) in aneurysmal subarachnoid hemorrhage. Here, we aim to assess whether racial differences exist in 1) presentation, 2) clinical course, and 3) outcomes, including time to blood pressure stabilization, for aSAH patients at a large tertiary care medical center. We conducted a retrospective review of adult aneurysmal subarachnoid hemorrhage cases from 2013 to 2019 at a single large tertiary medical center. Data extracted from the medical record included sex, age, race, insurance status, aneurysm location, aneurysm treatment, initial systolic and diastolic blood pressure, Hunt Hess grade, modified Fisher score, time to blood pressure control (defined as time in minutes from first blood pressure measurement to the first of three consecutive systolic blood pressure measurements under 140mmHg), hospital length of stay, and final discharge disposition. 194 patients met inclusion criteria; 140 (72%) White and 54 (28%) Black. While White patients were more likely than Black patients to be privately insured (62.1% versus 33.3%, p < 0.001), Black patients were more likely than White patients to have Medicaid (55.6% versus 15.0%, p < 0.001). Compared to White patients, Black patients presented with a higher median systolic (165 mmHg versus 148 mmHg, p = 0.004) and diastolic (93 mmHg versus 84 mmHg, p = 0.02) blood pressure. Black patients had a longer median time to blood pressure control than White patients (200 minutes versus 90 minutes, p = 0.001). Black patients had a shorter median hospital length of stay than White patients (15 days versus 18 days, p < 0.031). There was a small but statistically significant difference in modified Fisher score between black and white patients (3.48 versus 3.17, p = 0.04).There were no significant racial differences present in sex, Hunt Hess grade, discharge disposition, complications, or need for further interventions. Black race was associated with higher blood pressure at presentation, longer time to blood pressure control, but shorter hospital length of stay. No racial differences were present in aneurysmal subarachnoid hemorrhage associated complications or interventions.

Size of Craniectomy Predicts Approach-Related Shear Bleeding in Poor-Grade Subarachnoid Hemorrhage

Decompressive craniectomy is an option to decrease elevated intracranial pressure in poor-grade aneurysmal subarachnoid hemorrhage (SAH) patients. The aim of the present study was to analyze the size of the bone flap according to approach-related complications in patients with poor-grade SAH. We retrospectively analyzed poor-grade SAH patients (WFNS 4 and 5) who underwent aneurysm clipping and craniectomy (DC or ommitance of bone flap reinsertion). Postoperative CT scans were analyzed for approach-related tissue injury at the margin of the craniectomy (shear bleeding). The size of the bone flap was calculated using the De Bonis equation. Between 01/2012 and 01/2020, 67 poor-grade SAH patients underwent clipping and craniectomy at our institution. We found 14 patients with new shear bleeding lesion in postoperative CT scan. In patients with shear bleeding, the size of the bone flap was significantly smaller compared to patients without shear bleeding (102.1 ± 45.2 cm2 vs. 150.8 ± 37.43 cm2, p > 0.0001). However, we found no difference in mortality rates (10/14 vs. 23/53, p = 0.07) or number of implanted VP shunts (2/14 vs. 18/53, p = 0.2). We found no difference regarding modified Rankin Scale (mRS) 6 months postoperatively. In poor-grade aneurysmal SAH, the initial planning of DC-if deemed necessary -and enlargement of the flap size seems to decrease the rate of postoperatively developed shear bleeding lesions.

Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Matricellular proteins have been implicated in pathologies after subarachnoid hemorrhage (SAH). To find a new therapeutic molecular target, the present study aimed to clarify the relationships between serially measured plasma levels of a matricellular protein, secreted protein acidic and rich in cysteine (SPARC), and delayed cerebral ischemia (DCI) in 117 consecutive aneurysmal SAH patients with admission World Federation of Neurological Surgeons (WFNS) grades I-III. DCI developed in 25 patients with higher incidences of past history of hypertension and dyslipidemia, preoperative WFNS grade III, modified Fisher grade 4, spinal drainage, and angiographic vasospasm. Plasma SPARC levels were increased after SAH, and significantly higher in patients with than without DCI at days 7-9, and in patients with VASOGRADE-Yellow compared with VASOGRADE-Green at days 1-3 and 7-9. However, there were no relationships between plasma SPARC levels and angiographic vasospasm. Receiver-operating characteristic curves differentiating DCI from no DCI determined the cut-off value of plasma SPARC ≥ 82.1ng/ml at days 7 - 9 (sensitivity, 0.800; specificity, 0.533; and area under the curve, 0.708), which was found to be an independent determinant of DCI development in multivariate analyses. This is the first study to show that SPARC is upregulated in peripheral blood after SAH, and that SPARC may be involved in the development of DCI without angiographic vasospasm in a clinical setting.

Increased prevalence of blister aneurysm formation during the COVID-19 pandemic

BackgroundIntracranial blister aneurysms are a rare and an historically difficult to treat subset of aneurysms. They are distinct from typical saccular aneurysms with different pathophysiology and treatment options. MethodsA prospectively maintained database of subarachnoid hemorrhage patients was queried for those presenting prior to the pandemic (2017–2019), and those presenting during the height of the pandemic in our locality (2021). Aneurysm characteristics and patient demographics associated with rupture risk/formation were collected. Results334 aneurysmal subarachnoid hemorrhage patients were reviewed. 86 of these patients presented in 2021, with a statistically significant increase in the proportion of ruptured ICA blister aneurysms as compared to 2017–2019 (7/86, 8% vs 5/248, p = .02). Mean patient age, presenting grade, other aneurysm location proportions, aneurysm size, and incidence of delayed cerebral ischemia were not different between the groups. ConclusionsPatients presenting with SAH during the height of the SARS-CoV-2 pandemic in 2021 were more likely to have ICA blister type aneurysms.

Should individual timeline and serial CT/MRI panels of all patients be presented in acute brain insult cohorts? A pilot study of 45 patients with decompressive craniectomy after aneurysmal subarachnoid hemorrhage

PurposeOur review of acute brain insult articles indicated that the patients’ individual (i) timeline panels with the defined time points since the emergency call and (ii) serial brain CT/MRI slice panels through the neurointensive care until death or final brain tissue outcome at 12 months or later are not presented.MethodsWe retrospectively constructed such panels for the 45 aneurysmal subarachnoid hemorrhage (aSAH) patients with a secondary decompressive craniectomy (DC) after the acute admission to neurointensive care at Kuopio University Hospital (KUH) from a defined population from 2005 to 2018. The patients were indicated by numbers (1.–45.) in the pseudonymized panels, tables, results, and discussion. The timelines contained up to ten defined time points on a logarithmic time axis until death (n=25; 56%) or 3 years (n=20; 44%). The brain CT/MRI panels contained a representative slice from the following time points: SAH diagnosis, after aneurysm closure, after DC, at about 12 months (20 survivors).ResultsThe timelines indicated re-bleeds and allowed to compare the times elapsed between any two time points, in terms of workflow swiftness. The serial CT/MRI slices illustrated the presence and course of intracerebral hemorrhage (ICH), perihematomal edema, intraventricular hemorrhage (IVH), hydrocephalus, delayed brain injury, and, in the 20 (44%) survivors, the brain tissue outcome.ConclusionsThe pseudonymized timeline panels and serial brain imaging panels, indicating the patients by numbers, allowed the presentation and comparison of individual clinical courses. An obvious application would be the quality control in acute or elective medicine for timely and equal access to clinical care.

Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: Relationship with delayed cerebral ischemia and poor prognosis.

To assess differences in the clinical prognosis between different treatment timings in poor-grade (Hunt and Hess grade 4-5) aneurysmal subarachnoid hemorrhage patients. The treated 127 poor-grade aneurysmal subarachnoid hemorrhage patients were divided into three groups: early treatment within 2 days, treatment on days 3 to 10, and treatment for more than 10 days after the hemorrhage. Odd ratios with a 95% confidence interval were calculated in logistic regression for different timing strategies regarding delayed cerebral ischemia and poor prognosis at 3 months. Subgroup analyses were conducted to determine whether the different timing strategies affect the prognosis. Patients who received the treatment on days 3 to 10 were prone to develop delayed cerebral ischemia and poor prognosis at 3 months. Postponing treatment in patients older than 55 years or diagnosed with an intraventricular hematoma on the initial computed tomography scan may lead to poor prognosis, with the early intervention group as a reference. Early intervention in poor-grade aneurysmal subarachnoid hemorrhage is suggested to be implemented. The treatment on 3 to 10 days harbored the highest risk of poor prognosis; patients might benefit more from early intervention, especially for ones older than 55 years or diagnosed with an intraventricular hematoma.

A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping

IntroductionAneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use. Research questionThe study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH. Material and methodsIn this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment. ResultsTen patients across four dose groups were treated with NicaPlant® (3–13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm. Discussion and conclusionThe placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies.

Validation of the TDN grade in an independent cohort of aneurysmal subarachnoid haemorrhage patients

Validation of the TDN grade in an independent cohort of aneurysmal subarachnoid haemorrhage patients

Analysis of Factors Influencing Delayed Presentation in Japanese Patients with Subarachnoid Hemorrhage

Some aneurysmal subarachnoid hemorrhage (SAH) patients are delayed in their presentation. This can cause a washout of the subarachnoid hematoma and a potential misdiagnosis. As a result, they may suffer rerupture of the aneurysm and preventable deterioration. We investigated the factors that influence delayed SAH presentation. Aneurysmal SAH patients treated at 9 stroke centers from 2002 to 2020 were included. Age, gender, pre-SAH modified Rankin scale, World Federation of Neurological Surgeons grade, Fisher group, day of presentation, aneurysm treatment method, past history of cerebral stroke, comorbidity of hypertension and/or diabetes mellitus, and modified Rankin scaleat discharge were assessed retrospectively. We formed 2 groups based on the day of presentation after the onset of SAH: day 0-3 (early) and other (delayed). Logistic regression analyses detected the factors that influenced the day of presentation and outcome for SAH. A P- value <0.05 was considered significant. Delayed presentation comprised 282 cases (6.3%) of 4507 included cases. Logistic regression analyses showed that patients in an urban area, of male gender, low WFNS grade and low Fisher group correlated significantly with a delayed presentation. But delayed presentation did not influence outcome at discharge. Area of residency and gender correlated with delayed presentation after SAH in Japan. Urbanization, male gender, and mild SAH lead patients to delay presentation. The factors underlying these tendencies will be analyzed in a future prospective study.

Plasma Fibulin-5 Levels as an Independent Predictor of a Poor Outcome after an Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a poor-outcome disease with a delayed neurological exacerbation. Fibulin-5 (FBLN5) is one of matricellular proteins, some of which have been involved in SAH pathologies. However, no study has investigated FBLN5's roles in SAH. This study was aimed at examining the relationships between serially measured plasma FBLN5 levels and neurovascular events or outcomes in 204 consecutive aneurysmal SAH patients, including 77 patients (37.7%) with poor outcomes (90-day modified Rankin Scale 3-6). Plasma FBLN5 levels were not related to angiographic vasospasm, delayed cerebral ischemia, and delayed cerebral infarction, but elevated levels were associated with severe admission clinical grades, any neurological exacerbation and poor outcomes. Receiver-operating characteristic curves indicated that the most reasonable cut-off values of plasma FBLN5, in order to differentiate 90-day poor from good outcomes, were obtained from analyses at days 4-6 for all patients (487.2 ng/mL; specificity, 61.4%; and sensitivity, 62.3%) and from analyses at days 7-9 for only non-severe patient (476.8 ng/mL; specificity, 66.0%; and sensitivity, 77.8%). Multivariate analyses revealed that the plasma FBLN5 levels were independent determinants of the 90-day poor outcomes in both all patients' and non-severe patients' analyses. These findings suggest that the delayed elevation of plasma FBLN5 is related to poor outcomes, and that FBLN5 may be a new molecular target to reveal a post-SAH pathophysiology.