Aneurysmal Subarachnoid Hemorrhage Research Articles

The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death. Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified. Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects. The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study.

A two-sample Mendelian randomization (MR) analysis was utilized to assess the causal relationship between lipidomic profiles and the risk of intracranial aneurysms (IAs). Genetic variants related to lipidomic profiles (227 components) and IA [IA, aneurysmal subarachnoid hemorrhage (aSAH) only, unruptured IA (uIA) only] were obtained from published genome-wide association studies (GWASs) or the IEU Open GWAS project and used as instrumental variables for MR analysis. The inverse-variance weighted method was used in the primary analyses to derive causality estimates and was expressed as odds ratio (OR) with 95% confidence interval (CI). Of these 227 lipidomic profiles, only genetically predicted high levels of cholesterol to total lipids ratio in very small very-low-density lipoproteins (VLDL) [OR = 0.629 (95% CI, 0.504-0.786)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.637 (95% CI, 0.509-0.797)], ratio of docosahexaenoic acid to total fatty acids [OR = 0.691 (95% CI, 0.582-0.820)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.630 (95% CI, 0.522-0.760)] reduced the risk of aSAH, whereas genetically predicted high ratio of monounsaturated fatty acids to total fatty acids [OR = 1.471 (95% CI, 1.215-1.781)] increased the risk of aSAH. Moreover, genetically predicted high levels of cholesterol to total lipids ratio in very small VLDL [OR = 0.657 (95% CI, 0.542-0.798)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.663 (95% CI, 0.548-0.803)], free cholesterol to total lipids ratio in small VLDL [OR = 0.682 (95% CI, 0.560-0.832)], phospholipids to total lipids ratio in small VLDL [OR = 0.674 (95% CI, 0.548-0.830)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.678 (95% CI, 0.569-0.808)] reduced the risk of IA. The results of multivariable MR demonstrated that these causal associations persisted after adjusting for systolic blood pressure and cigarettes smoked per day. The effect of serum lipids on IA and aSAH may be mainly caused by subclasses of lipids such as VLDL.

Vasospasm management: a meta-synthesis of current modalities used by different medical societies

Background: Cerebral vasospasm is a life-threatening complication of an aneurysmal subarachnoid hemorrhage (aSAH), with approximately 6 to 10 cases per 100,000 patients yearly. Despite the publication of numerous guidelines from various medical societies, there is a lack of standardized consensus on what the optimal management strategies for this severe complication truly are. This meta-synthesis aims to synthesize these endorsed recommendations to ultimately identify standardized care guidelines and improve patient outcomes after aSAH. Methods: A comprehensive database search of existing guidelines published by major medical societies in the past 10 years was performed. Results: The analysis included 28 relevant documents from 7 major medical societies. Key findings included: 1) Unanimous endorsement for oral nimodipine administration for 21 days post-aSAH. 2) Varying recommendations for alternative calcium channel blockers and hemodynamic management methods. 3) Targeted hypermagnesemia and routine statin therapy were not universally recommended due to insufficient evidence. 4) Use of antifibrinolytics was considered on a case-by-case basis. 5) Endovascular interventions were recommended for refractory cases, specifically. Conclusion: This meta-synthesis reveals consistencies and divergences in vasospasm management recommendations across medical societies, highlighting the need for more robust clinical trials, regular guideline updates, and increased medical society collaboration. Keywords: Vasospasm, cerebral vasospasm, aSAH, management, guidelines, meta-synthesis

Trajectory of mean platelet volume changes after aneurysmal subarachnoid hemorrhage in patients with or without delayed cerebral ischemia

The morbidity of aneurysmal subarachnoid hemorrhage (aSAH) remains high, particularly because of secondary cerebral lesions that significantly aggravate the primary lesions. The main type of secondary lesions is delayed cerebral ischemia (DCI), in which platelets (PLT) appear to play a key role. Mean platelet volume (MPV) is an indirect marker of platelet activation. We aimed to determine the individual trajectories of MPV over time in patients with and without DCI during the course of aSAH. This is a single-center, retrospective, longitudinal analysis of individual trajectories of MPV over time, in a cohort of aSAH patients included in the Prospective, Observational Registry of Patient with Subarachnoid Hemorrhage in Neurocritical Care Unit (ProReSHA). A mixed-effects linear regression model was used to compare the trajectories of MPV and MPV/PLT ratio between patients who developed a DCI and those who did not. A total of 3634 MPV values were collected in 587 patients. The analysis of MPV as a function of DCI occurrence showed a significant difference in the trajectory over time between patients with DCI and those without, with an estimate of 0.02 (95%CI 0.01, 0.04, p = 0.009). The analysis of the MPV/PLT ratio as a function of DCI occurrence and other covariates showed a significant difference in the trajectory over time only for patients with a modified Fisher score less than 3, with an estimate of -0.59 (95%CI: -0.94, -0.23, p = 0.001). The individual trajectories of MPV over time differ between patients with DCI and those without. However, MPV values vary greatly over time and between patients. Thus it does not appear as a reliable biomarker for stratifying patients based on their specific risk of developing DCI. ClinicalTrials.gov identifier: (NCT02890004), registered in August 2016.

Identifying Patients at Increased Risk for Poor Outcomes Among Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients: The IPOGRO Risk Model

Background: A subarachnoid hemorrhage due to an aneurysmal rupture (aSAH) is a serious condition with severe neurological consequences. The World Federation of Neurosurgical Societies (WFNS) classification is a reliable predictor of death and long-term disability in patients with aSAH. Poor-grade neurological conditions on admission in aSAH (PG-aSAH) are often linked to high mortality rates and unfavorable outcomes. However, more than one-third of patients with PG-aSAH may recover and have good functional outcomes if aggressive treatment is provided. We developed a risk model called Identifying POor GRade Outcomes (IPOGRO) to predict 6-month mRS outcomes in PG-aSAH patients as a secondary analysis of a previously published study. Methods: All consecutive patients in poor-grade neurological conditions (WFNS IV-V) admitted to our institute from 2010 to 2020 due to aSAH were considered. Clinical and neuroradiological parameters were employed in the univariable analysis to evaluate the relationship with a 6-month modified Rankin Scale (mRS). Then, a multivariable multinomial regression model was performed to predict 6-month outcomes. Results: 149 patients with PG-aSAH were included. Most patients were surgically treated, with only 33.6% being endovascularly treated. The 6-month mRS score was significantly associated with clinical parameters on admission, such as lowered Glasgow Coma Scale (GCS), leukocytosis, hyperglycemia, raised Systolic Blood Pressure (SBP), greater Simplified Acute Physiology Score (SAPS II score), increased initial serum Lactic Acid (LA) levels, and the need for Norepinephrine (NE) administration. Neuroradiological parameters on the initial CT scan showed a significant association with a worsening 6-month mRS. The IPOGRO risk model analysis showed an association between a WFNS V on admission and a poor outcome (mRS 4-5), while raised SBP was associated with mortality. Conclusions: Our IPOGRO risk model indicates that PG-aSAH patients with higher SBP at admission had an increased risk of death at 6-month follow-up, whereas patients with WFNS grade V at admission had an increased risk of poor outcome but not mortality.

Clinical Development of the GluN2B-selective NMDA Receptor Inhibitor NP10679 for the Treatment of Neurologic Deficit after Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) may be associated with cerebral vasospasm, which can lead to delayed cerebral ischemia, infarction, and worsened functional outcomes. The delayed nature of cerebral ischemia secondary to SAH-related vasculopathy presents a window of opportunity for the evaluation of well-tolerated neuroprotective agents administered soon after ictus. Secondary ischemic injury in SAH is associated with increased extracellular glutamate, which can overactivate NMDA receptors (NMDARs), thereby triggering NMDAR-mediated cellular damage. In this study, we have evaluated the effect of the pH-sensitive GluN2B-selective NMDAR inhibitor, NP10679, on neurologic impairment after SAH. This compound demonstrates a selective increase in potency at the acidic extracellular pH levels that occur in the setting of ischemia. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care. In addition, we observed an unexpected reduction in SAH-induced luminal narrowing of the middle cerebral artery. Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. Based on allometric scaling of both toxicological and efficacy data, the therapeutic margin in man should be at least 2. These results further demonstrate the utility of pH-dependent neuroprotective agents and GluN2B-selective NMDAR inhibitors as potential therapeutic strategies for the treatment of aSAH. Significance Statement This report describes the properties and utility of the GluN2B-selective pH-sensitive NMDA receptor inhibitor, NP10679, in a well-characterized rodent model of subarachnoid hemorrhage. We show that the administration of NP10679 improves long-term neurological function following subarachnoid hemorrhage, and that in rats there are no drug-drug interactions between NP10679 and nimodipine, the standard of care for this indication.

Development and Validation of a Prechiasmatic Mouse Model of Subarachnoid Hemorrhage to Measure Long-Term Cognitive Deficits.

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced significant and trackable long-term cognitive deficits. SAH is induced by performing double blood injections into the prechiasmatic cistern - a simple modification to the well-characterized single prechiasmatic injection mouse model of SAH. Following SAH, mice recapitulated key characteristics of SAH patients, including cerebral edema measured by MRI - an indicator of early brain injury (EBI), neuroinflammation, apoptosis, and long-term cognitive impairment.This newly developed SAH mouse model is considered an ideal paradigm for investigating the complex SAH pathophysiology and identifying novel druggable therapeutic targets for treating SAH severity and SAH-associated long-term neurocognitive deficits in patients.

Prescribed Drug Use and Aneurysmal Subarachnoid Hemorrhage Incidence: A Drug-Wide Association Study.

Prescribed Drug Use and Aneurysmal Subarachnoid Hemorrhage Incidence: A Drug-Wide Association Study.

Can the radiomics features of intracranial aneurysms predict the prognosis of aneurysmal subarachnoid hemorrhage?

ObjectivesThis study attempted to determine potential predictors among radiomics features for poor prognosis in aneurysmal subarachnoid hemorrhage (aSAH), develop models for prediction, and verify their predictive power.MethodsIn total, 252 patients with aSAH were included in this study and categorized into favorable and poor outcome groups based on the modified Rankin Scale score 3 months after event. Radiomics features of the ruptured intracranial aneurysm extracted from computed tomography angiography images were selected using least absolute shrinkage and selection operator regression and 10-fold cross-validation. A radiomics score was created by selecting the optimal features. Other risk factors for a poor prognosis were screened using multivariate regression analysis. Three models (clinical, aneurysm, and clinical-aneurysm combined models) were developed. The performance of the models was assessed using receiver operating characteristic (ROC) curves. A clinical-aneurysm combined nomogram was constructed to forecast the risk of poor prognosis in patients with aSAH.ResultsA total of three clinical variables and six radiomics features were shown to have a significant association with poor prognosis in patients with aSAH. In the training cohort, the clinical, aneurysm, and clinical-aneurysm combined models had areas under the ROC curves of 0.846, 0.762, and 0.893, respectively. In the testing cohort, these models had areas under the ROC curves of 0.848, 0.753, and 0.869, respectively.ConclusionThe radiomics characteristics of ruptured intracranial aneurysms are valuable to predict prognosis after aSAH. The clinical-aneurysm combined model exhibited the best among the three models. The clinical-aneurysm combined nomogram is a reliable and effective tool for predicting poor prognosis in patients with aSAH.

Early mobilization in patients with aneurysmal subarachnoid haemorrhage may im-prove functional status and reduce cerebral vasospasm rate: a systematic review with meta-analysis.

The primary aim of this study was to evaluate the safety and efficacy of early mobilization in patients with aneurysmal subarachnoid haemorrhage. Systematic review with meta-analysis of randomized controlled studies and observational studies. Patients with aneurysmal subarachnoid haemorrhage. PubMed, Embase, CINAHL, Web of Science, Pedro, and the Cochrane Library databases were searched. A systematic review and meta-analysis were performed. Screening and data extraction were performed by 2 independent reviewers. Sixteen studies involving 1,757 patients were included. Meta-analysis of the data estimated that early mobilization improved mRS score at discharge (mean difference -1.39, 95% CI -2.51 to -0.28, I2 = 86%) and at 3 months (mean difference -1.10, 95% CI -1.54 to -0.66, I2 = 7%). Early mobilization was associated with a reduction in cerebral vasospasm rate, both radiological (OR 0.66, 95% CI 0.45 to 0.96, I2 = 7%) and clinical (OR 0.44, 95% CI 0.27 to 0.72, I2 = 8%); 6% of mobilization sessions involved adverse events, mostly haemodynamic changes. This review found moderate-quality evidence supporting the safety and effectiveness of early mobilization in patients with SAH. Further randomized controlled trials are needed to identify the appropriate mobilization strategy and confirm these results.

Treatment of Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage Using the Compliant Manually Adjustable Mesh Comaneci.

Background and purpose: Cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH) may lead to morbidity and mortality. Endovascular mechanical angioplasty may be performed if symptomatic CV is refractory to noninvasive medical management. Compliant and noncompliant balloons and manually adjustable mesh may be used in this indication. We describe our initial experience with the Comaneci (Rapid Medical, Yokneam, Israel) in cerebral vasospasm treatment following aSAH. Methods: All patients included in the prospective observational SAVEBRAIN PWI (NCT05276934 on clinicaltrial.gov) study who underwent cerebral angioplasty using the Comaneci device for the treatment of medically refractory and symptomatic CV after aSAH were identified. Patient demographic information, procedural details, and outcomes were obtained from electronic medical records. Results: Between February 2022 and June 2023, seven consecutive patients underwent CV treatment with the Comaneci. Angioplasty of 37 arterial segments (supraclinoid internal carotid artery, A1, A2, and A3 segments of the anterior cerebral artery and M1 and M2 segments of the middle cerebral artery) was attempted, and 35/37 (95%) were performed. The vessel diameter improved significantly following angioplasty (+64%), while brain hypoperfusion decreased (-45% of the mean T Max). There was no long-term clinical complication, and 6% per-procedural complications occurred. Conclusions: The Comaneci is effective in the treatment of cerebral vasospasm following aSAH, bringing a new device in the armamentarium of the neurointerventionalist to perform intracranial angioplasty.

Serum sodium concentration predicting mortality in patients with aneurysmal subarachnoid hemorrhage

BackgroundTo date, inconsistent evidence exists on the role of hypernatremia in patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent surgical clipping. We aimed to investigate the association between serum sodium and mortality in these patients. MethodsA cohort study was performed to include adult patients with aSAH who underwent surgical clipping in a university hospital. The primary outcome was follow-up mortality. Propensity score matching (PSM) was used for matching patients’ baseline characteristics. Net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess and compare the reclassification and discrimination capacity of different models. Trends in serum sodium over time were detected by the ordinary least squares model. ResultsOf 618 aSAH patients with surgical clipping during the study period, normal serum sodium was observed in 467 patients (75.6 %), and admission hypernatremia was noted in 151 patients (24.4 %). After adjustment with multivariate regression analysis, patients with hypernatremia had significantly higher odds for follow-up mortality (aOR: 2.86, 95 % CI: 1.54 to 5.30; P = 0.001). PSM analysis observed similar results (aOR: 2.38, 95 % CI: 1.29 to 4.55; P = 0.009). The incorporation of serum sodium during hospitalization markedly enhanced the IDI (P < 0.001) and NRI (P < 0.001) for the prediction of mortality. ConclusionsIn conclusion, the findings from this cohort study of aSAH patients with surgical clipping indicated that serum sodium can be an independent predictive factor of all-cause mortality, and inferior sequelae in aSAH patients. These findings endorsed the importance of managing hypernatremia and monitoring serum sodium in patients with aSAH.

Elevated Blood Pressure and Culprit Aneurysm Rebleeding During the Unsecured Period of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review.

In aneurysmal subarachnoid hemorrhage, rebleeding prior to securing the culprit aneurysm leads to significant morbidity and mortality. Elevated blood pressure has been identified as a possible risk factor. In this systematic review, we evaluated the association between elevated blood pressure and aneurysm rebleeding during the unsecured period. We searched MEDLINE, Embase + Embase Classic, and CENTRAL, from inception to March 8th, 2024. We included studies of adults with aneurysmal subarachnoid hemorrhage reporting at least one blood pressure measurement during the unsecured period and a measure of association with rebleeding. Results were stratified by blood pressure thresholds, effect measure, and adjustment for confounding. Separate meta-analyses were performed for each of these groups. Our search identified 5,209 citations. After screening, 15 studies were included in our review. All studies were observational in design and at moderate or high risk of bias. Meta-analysis of the unadjusted results produced mixed findings across the systolic blood pressure (SBP) thresholds: SBP > 140mmHg, unadjusted odds ratio (uOR) 1.03 (95% confidence interval [CI] 0.55-1.93; I2 = 66%); SBP > 160mmHg, uOR 3.35 (95% CI 1.44-7.81; I2 = 83%); SBP > 180mmHg, uOR 1.52 (95% CI 0.40-5.81; I2 = 89%); and SBP > 200mm Hg, uOR 7.99 (95% CI 3.60-17.72; I2 = 0%). Meta-analysis of adjusted results was only possible at an SBP > 160mmHg; adjusted hazard ratio 1.13 (95% CI 0.98-1.31; I2 = 0%). The overall quality of evidence as assessed by the Grading of Recommendations, Assessment, Development, and Evaluations tool was rated as very low. Based on very low quality evidence, our systematic review failed to determine whether there is an association between elevated blood pressure during the unsecured period and increased risk of culprit aneurysm rebleeding.

Age-Related Differences in Clinical Characteristics and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Retrospective Study of 657 Patients

Aneurysmal subarachnoid hemorrhage (aSAH) has an incidence of 6-7 per 100,000 person-years. Despite advancements in treatment, 26% of patients die, and 19% remain dependent post-hemorrhage. Long-term neuropsychological sequelae affect about half of the survivors, significantly impacting their quality of life. This study aims to assess aSAH characteristics and identify predictive factors of clinical outcomes in young patients. A retrospective study analyzed 657 aSAH patients treated at two South Korean medical centers from January 2011 to December 2023. Data on demographics, comorbidities, smoking history, clinical grades, aneurysm size and location, and outcomes were collected. Outcomes were classified using the modified Rankin Scale (mRS), with scores ≤2 indicating good outcomes. The cohort included 233 men and 424 women (male-to-female ratio 1:1.8). Most patients were middle-aged (74.4%), followed by young (16.7%) and old (8.8%) groups. Young patients exhibited male predominance (56.8%), lower hypertension (12.7%) and diabetes (1.8%) rates, and higher smoking rates (39.6%). Older patients had higher hypertension (44.6%) and diabetes (23.3%) rates, and were predominantly female (69.1%). Aneurysms in young patients were smaller (p=0.04). Multivariate analysis identified poor Hunt-Hess grade, permanent cerebral infarction, and aneurysmal recurrence or rebleeding as predictors of poor outcomes in young patients. Middle-aged patients had additional predictors, including diabetes and hydrocephalus. In older patients, only poor Hunt-Hess grade was significant. Young aSAH patients exhibit distinct characteristics and prognostic factors compared to older patients. Despite higher post-operative complications, young patients generally have better outcomes, emphasizing the need for age-specific management strategies in aSAH.

Higher erythrocytes in cerebrospinal fluid on the first and seventh postoperative day: Associated with poor outcome in aneurysmal subarachnoid hemorrhage patients.

Aneurysmal subarachnoid hemorrhage is an acute cerebrovascular disease with high disability and mortality. We intended to explore the association between levels of erythrocytes in cerebrospinal fluid at different times of hemorrhage and the outcome of patients. One retrospective study including 216 patients with aneurysmal subarachnoid hemorrhage undergoing surgeries in the First Affiliated Hospital of Yangtze University from January 2020 to July 2023 was carried. The univariable analysis and multivariable logistic regression analysis were used for factors associated with poor outcome. The level of erythrocytes in cerebrospinal fluid on the 1st postoperative day in patients with poor outcome was 311 × 103/µL, significantly higher than patients with good outcome (108 × 103/µL), P < .001. The level of erythrocytes in cerebrospinal fluid on 7th postoperative day was 86.5 × 103/µL, also significantly higher than patients with good outcome (26.0 × 103/µL). The multivariable logistic regression analysis results showed that erythrocytes in cerebrospinal fluid on the 1st postoperative day (≥177 × 103/µL) and on the 7th postoperative day (≥53.5 × 103/µL) were possibly associated with poor outcome in aneurysmal subarachnoid hemorrhage patients. Treatment with tranexamic acid and continuous lumbar drainage did not result in a decrease of erythrocytes in cerebrospinal fluid. Higher erythrocytes in cerebrospinal fluid on the 1st and 7th postoperative days were associated with poor outcome in aneurysmal subarachnoid hemorrhage patients.

Energy Expenditure in Critically Ill Patients with Aneurysmal Subarachnoid Hemorrhage, Intracerebral Hemorrhage, and Traumatic Brain Injury-A Prospective Observational Study.

Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls. A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2-3, 5-7, and 10-15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t-tests, Chi-square tests, and generalized mixed models. We included 110 patients-43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH-interventional (p = 0.003) and versus the control (p = 0.004), as well as at timepoint 2 for ICH versus SAH-interventional (p = 0.002) and versus SAH-surgical (p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine. In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase.

Impact of intracranial atherosclerosis burden on vasospasm risk and outcomes in aneurysmal subarachnoid hemorrhage

BackgroundCerebral vasospasm is a well-known complication after aneurysmal subarachnoid hemorrhage (aSAH) and occurs more commonly in younger patients. We hypothesized that intracranial atherosclerosis, which is seen predominantly in older patients, affects vasospasm risk. We sought to determine association between intracranial atherosclerosis burden with vasospasm and outcomes in aSAH. MethodsWe retrospectively reviewed a cohort of consecutive patients with aSAH admitted to a Comprehensive Stroke Center between 2016 and 2023. Intracranial atherosclerosis burden was quantified by using modified Woodcock (MW) score on CT angiograms. Vasospasm was defined based on transcranial Doppler (TCD) criteria. Poor outcome was defined as 3-month modified Rankin Scale 3–6. ResultsWe reviewed 392 patients and included 302 (mean age 56.8 years [SD 13.3], 65 % female and 70 % white) in the final analysis. MW scores were measured with excellent intra-rater and inter-rater reliability (Cohen's kappa coefficient 0.9 and 0.83 respectively) ranging from 0 to 3 (mean 0.59, SD 0.83) with higher scores in older patients (beta coefficient 0.019, 95 % CI 0.009–0.028; p < 0.001). Higher MW calcification score was associated with lower risk of vasospasm (OR 0.52 per point increase, 95 % CI 0.36–0.78; p = 0.001). There was an inverse correlation between MW scores and severity of vasospasm (beta coefficient −0.29, 95 % CI −0.48, −0.1; p = 0.003). However, MW score was not independently associated with poor functional outcome (p = 0.62). ConclusionsIntracranial atherosclerosis is a potential mechanism for lower TCD-based vasospasm in older patients with aSAH; however, it may not impact functional outcomes. Larger prospective studies are needed to confirm our findings.

Brain hypoxia and metabolic crisis are common in patients with acute brain injury despite a normal intracranial pressure

Patients with acute brain injury are vulnerable to secondary deterioration, which may go undetected by traditional monitoring. However, multimodal neuromonitoring of brain tissue oxygen tension (PbtO2) and energy metabolism may be able to detect such episodes. We report a retrospective, observational study of 94 patients with aneurysmal subarachnoid haemorrhage (SAH) or traumatic brain injury (TBI) who underwent multimodal neuromonitoring during admission. We examined the co-occurrence of pathological neuromonitoring values: elevated intracranial pressure (ICP, > 20 mmHg), inadequate cerebral perfusion pressure (CPP, < 60 mmHg), brain hypoxia (PbtO2 < 20 mmHg), and metabolic crisis (lactate/pyruvate ratio > 40 and a glucose level < 0.2 mmol/L in cerebral microdialysate). Mixed effects linear regression demonstrated significant associations between abnormal ICP/CPP, cerebral hypoxia and metabolic crisis. However, brain hypoxia occurred in 40% and 31% of observations in patients with SAH and TBI, respectively, despite normal concurrent values of ICP. Similarly, metabolic crisis was observed in 8% and 16% of measurements for SAH and TBI, respectively, despite a normal ICP. The pattern was identical for CPP. In conclusion, although all neuromonitoring variables are interrelated, brain hypoxia and metabolic crisis are common despite an absence of abnormalities in conventional monitoring. Multimodal neuromonitoring may help identify such episodes and guide individualised treatment.

The ABCs of Subarachnoid Hemorrhage Blood Volume Measurement: A Simplified Quantitative Method Predicts Outcomes and Delayed Cerebral Ischemia.

We developed a simplified ABC/2-derived method to estimate total subarachnoid hemorrhage volume (SAHV) on noncontrast computed tomography in patients with aneurysmal SAH and compared the clinical and radiographic outcomes. In this retrospective observational cohort study, we analyzed 277 patients with SAH admitted to our Comprehensive Stroke Center between 2012 and 2022. We derived a mathematical model (model 1) by measuring SAH basal cisternal blood volume using an ABC/2-derived ellipsoid formula (A=width/thickness, B=length, C=vertical extension) on head noncontrast computed tomography in 5 major SAH cisternal compartments. We compared model 1 against a manual segmentation method (model 2) on noncontrast computed tomography. Data were analyzed using logistic regression analysis, t test, receiver operator characteristic curves, and area under the curve analysis. There was no significant difference in cisternal SAHV analysis between the 2 models (P=0.14). Mean SAHV by the simplified method was 7.0 mL (95% CI, 5.89-8.09) for good outcome and 16.6 mL (95% CI, 13.49-19.77) for poor outcome. Patients with delayed cerebral ischemia had higher SAHV, with a cutoff value of 10 mL. Our simplified ABC/2-derived method to estimate SAHV is comparable to manual segmentation and can be performed in low-resource settings. Higher total SAHV was associated with worse outcomes and higher risk of delayed cerebral ischemia. A potential dose-response relationship was observed, with SAHV >10 mL predicting worse outcomes and higher risk of DCI.