12/15-Lipooxygenase Inhibition Reduces Microvessel Constriction and Microthrombi after Subarachnoid Hemorrhage in Mice.

Background and Purpose: Impaired cerebral circulation, induced by blood vessel constrictions and microthrombi, leads to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). 12/15-Lipooxygenase (12/15-LOX) overexpression has been implicated in worsening early brain injury outcomes following SAH. However, it is unknown if 12/15-LOX is important in delayed pathophysiological events after SAH. Since 12/15-LOX produces metabolites that induce inflammation and vasoconstriction, we hypothesized that 12/15-LOX leads to microvessel constriction and microthrombi formation after SAH, and thus 12/15-LOX is an important target to prevent delayed cerebral ischemia. Methods: SAH was induced in C57BL/6 and 12/15-LOX-/- mice of both sexes by endovascular perforation. Expression of 12/15-LOX was assessed in brain tissue slices and in vitro. C57BL/6 mice were administered either ML351 (12/15-LOX inhibitor) or vehicle. Mice were evaluated for daily neuroscore and euthanized on day five to assess cerebral 12/15-LOX expression, vessel constrictions, platelet activation, microthrombi, neurodegeneration, infarction, cortical perfusion, and for development of delayed deficits. Finally, the effect of 12/15-LOX inhibition on platelet activation was assessed in SAH patient samples using a platelet spreading assay. Results: In SAH mice, 12/15-LOX was upregulated in brain vascular cells and there was an increase in 12-S-HETE. Inhibition of 12/15-LOX improved brain perfusion on days 4-5 and attenuated delayed pathophysiological events, including microvessel constrictions, microthrombi, neuronal degeneration, and infarction. Additionally, 12/15-LOX inhibition reduced platelet activation in human and mouse blood samples. Conclusions: Cerebrovascular 12/15-LOX overexpression plays a major role in brain dysfunction after SAH by triggering microvessel constrictions and microthrombi formation, which reduces brain perfusion. Inhibiting 12/15-LOX may be a therapeutic target to improve outcomes after SAH.

Microneurosurgery for Ruptured Aneurysm of Distal Intracranial Vertebral Artery: A Case Report.

The International Subarachnoid Aneurysm Trial led to a shift from clipping to endovascular coiling as the primary therapy for cerebral aneurysm particularly in the management of posterior circulation aneurysm. However, endovascular therapy is often unavailable in low-resource settings, emphasizing the importance of maintaining surgical skill sets in resource-poor countries. This article presents a detailed case report on the successful microneurosurgical management of a 65-year-old female with a history of headache and weakness with past history of hypertension and a right posterior cerebral artery territory infarct who was diagnosed with a ruptured aneurysm situated within the intracranial vertebral artery. Patient was operated with the far lateral approach and clipping of the aneurysm. This case report elucidates the intricate surgical techniques employed, and the challenges neurosurgeons encountered in treating posterior circulation intracranial aneurysms, particularly those with ruptured complications. The aneurysms' intricate anatomy and increased rupture risk necessitate a meticulous microneurosurgical approach. The severity of subarachnoid hemorrhage from ruptured aneurysms increases morbidity and mortality rates.

Rare presentation of Klüver-Bucy syndrome following subarachnoid hemorrhage.

Background: Klüver-Bucy syndrome (KBS) is a rare neuropsychiatric disorder, and it can be associated with a variety of neurological disorders. It is characterized by visual agnosia, placidity, hyperorality, hypersexuality, dietary changes, amnesia, and hypermetamorphosis. KBS is mainly a clinical diagnosis, with at least three symptoms sufficient to diagnose the condition. Case Description: The case describes a 49-year-old Filipino woman with a history of hypertension who presented with symptoms strongly suggesting KBS following subarachnoid hemorrhage, including behaviors such as hyperorality, hypermobility, placidity, hypermetamorphosis, and hypersexuality along with memory disturbance. She was managed as a case of brief psychotic disorder initially with olanzapine, then on the second presentation as a case of delirium with risperidone. Conclusion: Among many symptoms of KBS, only three symptoms are required for the diagnosis clinically. Numerous neurological conditions can cause KBS. Symptomatic treatment is the mainstream treatment currently for KBS.[3] While different differential diagnoses are present, neurologists, psychiatrists, neurosurgeons, and radiologists should collaborate and be vigilant for the diagnosis of KBS, especially with the presence of one of its etiologies.

Ruptured distal anterior inferior cerebellar artery aneurysm years after stereotactic radiosurgery for vestibular schwannoma: A case report and literature review.

Background: Aneurysmal formation after stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) is a rare complication. Its characteristics and the best treatment strategies remain controversial, and the clinical course is especially unknown because reported aneurysms are first incidentally detected, or aneurysmal rupture occurs suddenly, and they are treated immediately. Case Description: A 68-year-old man who underwent SRS for VS 20 years ago presented with subarachnoid hemorrhage (SAH) due to rupture of a radiation-induced fusiform anterior inferior cerebellar artery aneurysm. He was treated with parent artery occlusion, resulting in a modified Rankin scale grade 2. This report illustrates the first case of detected aneurysm formation before rupture with retrospective magnetic resonance imaging evaluation. Conclusion: We describe the possible risk of rapid progression and rupture of aneurysms, focusing on the interval from SRS to aneurysmal formation. The period of formation of SRS-induced aneurysms is suspected to vary from years to decades regardless of radiation doses; however, aneurysms estimated as pseudoaneurysms have an extremely high risk of rupture within a few years, even when small in size. If aneurysms are discovered unruptured, there are some advantages in not only the prevention of poor prognosis due to SAH but also in the availability of optional therapeutic strategies using revascularization. Long-term annual follow-up, including vessel examination, is warranted not only to assess tumor status but also for early detection of any vascular lesions.

Beyond nimodipine: advanced neuroprotection strategies for aneurysmal subarachnoid hemorrhage vasospasm and delayed cerebral ischemia.

The clinical management of aneurysmal subarachnoid hemorrhage (SAH)-associated vasospasm remains a challenge in neurosurgical practice, with its prevention and treatment having a major impact on neurological outcome. While considered a mainstay, nimodipine is burdened by some non-negligible limitations that make it still a suboptimal candidate of pharmacotherapy for SAH. This narrative review aims to provide an update on the pharmacodynamics, pharmacokinetics, overall evidence, and strength of recommendation of nimodipine alternative drugs for aneurysmal SAH-associated vasospasm and delayed cerebral ischemia. A PRISMA literature search was performed in the PubMed/Medline, Web of Science, ClinicalTrials.gov, and PubChem databases using a combination of the MeSH terms "medical therapy," "management," "cerebral vasospasm," "subarachnoid hemorrhage," and "delayed cerebral ischemia." Collected articles were reviewed for typology and relevance prior to final inclusion. A total of 346 articles were initially collected. The identification, screening, eligibility, and inclusion process resulted in the selection of 59 studies. Nicardipine and cilostazol, which have longer half-lives than nimodipine, had robust evidence of efficacy and safety. Eicosapentaenoic acid, dapsone and clazosentan showed a good balance between effectiveness and favorable pharmacokinetics. Combinations between different drug classes have been studied to a very limited extent. Nicardipine, cilostazol, Rho-kinase inhibitors, and clazosentan proved their better pharmacokinetic profiles compared with nimodipine without prejudice with effective and safe neuroprotective role. However, the number of trials conducted is significantly lower than for nimodipine. Aneurysmal SAH-associated vasospasm remains an area of ongoing preclinical and clinical research where the search for new drugs or associations is critical.

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

BACKGROUND: Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. METHODS: A total of 472 patients admitted within 72 h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). RESULTS: Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). CONCLUSIONS: Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Impact of frailty on post-operative outcomes following subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and morbidity, particularly among elderly patients. The presence of frailty may impact survival rates in patients with SAH. In this study, we aim to investigate the impact of frailty on the clinical outcomes in SAH patients. METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Relevant papers through December 2023 were retrieved from PubMed, Scopus, Web of science, and Embase. RESULTS: A total of 5 studies met inclusion/exclusion criteria with an aggregate 39,221 non-frail patients (mean age 52.4 ± 5.2 yr; 62.1 % Female), and 79,416 frail patients (mean age 61.1 ± 5.4 yr; 69.0 % Female). Frailty was significantly associated with higher mortality ratio (Odds ratio (OR)= 2.09; CI [1.04: 4.20], p= 0.04), and increased length of hospital stay (OR= 1.40; CI [1.07: 1.83], p= 0.015). Additionally, frailty was associated with higher odds of external ventricular drain insertion, the need of tracheostomy/endoscopic gastrostomy, increased risk of deep vein thrombosis, and postoperative neurological complications. CONCLUSION: Frailty is associated with worse clinical outcomes and higher mortality rates in SAH patients. Our findings highlight that frailty, when considered alongside other established prognostic factors, serves as crucial predictor for peri-operative complications and overall hospital course in SAH patients.

Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

Pituitary Apoplexy: Pitfalls in Diagnosis.

Headache is a common presenting complaint in the emergency department. A rare cause is pituitary apoplexy - a complication of pituitary adenoma consisting of hemorrhage or infarction of the primary tumor accounting for approximately 1 % of headaches. A 44-year-old female presented with intractable headache, nausea, photophobia and later - signs of meningeal irritation. Initial imaging demonstrated no mass or hemorrhage, labs showed only leukocytosis and elevated CRP. Patient was started on empiric acyclovir and methylprednisolone. CSF analysis was negative for meningitis, thus MRI of the brain was performed which demonstrated a 2.5 cm suprasellar mass. Initial Pituitary hormone evaluation demonstrated low prolactin, normal TSH and low ACTH thought to be due to steroid use. Repeat laboratory evaluation demonstrated hypopituitarism. Patient underwent resection of the adenoma with pathology consistent with pituitary apoplexy. We highlight the need for careful evaluation of patients presenting with headache and signs of meningeal irritation given 16 % prevalence of pituitary adenoma. CT of the head may not always demonstrate acute infarction, with MRI of the brain remaining the most sensitive imaging modality. Given the common use of methylprednisolone for headache, a pitfall in the diagnosis of pituitary apoplexy includes proper assessment of a pituitary panel prior to initiation of steroids.

A prognostic model incorporating the albumin-corrected anion gap in patients with aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) patients typically have poor prognoses. The anion gap (AG) has been proven to correlate with mortality in various critically ill patients. However, hypoalbuminemia can lead to underestimations of the true anion gap levels. This study was conducted to verify the prognostic value of single AG and albumin-corrected anion gap (ACAG) among aSAH patients. Methods: Significant factors in the univariate logistic regression analysis were included in the multivariate logistic regression analysis to explore the risk factors for mortality in aSAH patients and to confirm the independent relationship between ACAG and mortality. The restricted cubic spline (RCS) was used to visually show the relationship between ACAG level and mortality risk of aSAH patients. The predictive model for mortality was developed by incorporating significant factors into the multivariate logistic regression analysis. The prognostic value of ACAG and the developed model was evaluated by calculating the area under the receiver operating characteristics curve (AUC). Results: Among 710 aSAH patients, a 30-day mortality was observed in 20.3% of the cases. A positive relationship was demonstrated between the ACAG level and mortality in aSAH patients using the RCS curve. The multivariate logistic regression analysis helped discover that only six factors were finally and independently related to mortality of aSAH patients after adjusting for confounding effects, including the Hunt-Hess scale score (p = 0.006), surgical options (p < 0.001), white blood cell count (p < 0.001), serum chloride levels (p = 0.023), ACAG (p = 0.039), and delayed cerebral ischemia (p < 0.001). The AUC values for the AG, albumin, and ACAG in predicting mortality among aSAH patients were 0.606, 0.536, and 0.617, respectively. A logistic regression model, which includes the Hunt-Hess scale score, surgical options, white blood cell count, serum chloride levels, ACAG, and delayed cerebral ischemia, achieved an AUC of 0.911 for predicting mortality. Conclusion: The ACAG is an effective prognostic marker for aSAH patients. A prognostic model incorporating ACAG could help clinicians evaluate the risk of poor outcomes among aSAH patients, thereby facilitating the development of personalized therapeutic strategies.

Transcranial Doppler in the Detection of Cerebral Vasospasm After Subarachnoid Hemorrhage.

Background Transcranial Doppler (TCD) is a simple, noninvasive, nonionizing, portable technique but not widely practiced to detect cerebral vasospasm after subarachnoid hemorrhage (SAH). Objective The aim of this study was to assess the performance of TCD in the detection of cerebral vasospasm in patients with SAH considering CT angiography (CTA) as a gold standard. Methods and material This cross-sectional study included 50 patients with acute SAH admitted to the National Institute of Neurosciences & Hospital (NINS & H), Dhaka, Bangladesh, from February to June 2021. The neurological status, severity of SAH, and initial CT findings were recorded. All patients were screened for cerebral vasospasm with TCD on the 4th, 7th, 10th, and 14th days after the event. Screening of cerebral vasospasm by CTA was done on the 14th day of the event or earlier if TCD suggested vasospasm. Results The mean age of the participants was 51.4 ±13.4 years (mean ± SD), and females were predominant (N=29, 58%). CTA detected cerebral vasospasm in 18 (36%) participants, but TCD could detect it in only 13 (26%) cases. Among the participants who had no vasospasm by CTA, all but one were also found to have no vasospasm by TCD. The agreement between TCD and CTA in detecting cerebral vasospasm was significant (p<0.001, κ=0.726). TCD shows good specificity (96.9%) and positive predictive value (92.8%), but sensitivity (72.2%) and negative predictive value (81.6%) were comparatively lower. Overall, the diagnostic accuracy of TCD in detecting cerebral vasospasm was 88%. Conclusions Although compared to CTA, TCD is a highly specific but less sensitive tool in detecting vasospasm, TCD remains a reliable screening tool for detecting vasospasm following SAH.

Acute Kidney Injury in Subarachnoid Hemorrhage: Exploring its Clinical Significance and Prognostic Implications.

OBJECTIVES: Subarachnoid hemorrhage (SAH) from spontaneous rupture of an aneurysm is a debilitating condition with high morbidity and mortality. Patients with SAH remain understudied, particularly concerning the evaluation of incidence and consequences of subsequent acute kidney injury (AKI). In this study, we aim to explore the risk factors and outcomes of AKI in patients with SAH. MATERIALS AND METHODS: International Classification of Diseases, 9th Edition and 10th Edition (ICD-10-CM) codes were used to query the National Inpatient Sample (NIS) for patients with a diagnosis of SAH between 2010-2019. Subgroup analysis was stratified by AKI diagnosis during the same hospitalization. AKI and non-AKI groups were assessed for baseline clinical characteristics, interventions, complications, and outcomes. Descriptive statistics, multivariate regressions, and propensity score-matching were performed using IBM SPSS 28. NEED TO MENTION NIH-SSS RESULTS: Of 76,553 patients diagnosed with nontraumatic SAH between 2010-2019, 10,634 (13.89%) had a comorbid diagnosis of AKI. Patients with AKI were older (p<0.01) and more often obese (p < 0.01), compared to the non-AKI group. A multivariate regression found the diagnosis of AKI to be independently correlated with poor functional outcome (p<0.001), above average length of stay (p < 0.001), and in-hospital mortality (p < 0.001) when controlling for age, SAH severity, and other comorbidities. CONCLUSIONS: This study showed significant association between AKI and adverse outcomes in SAH patients, and a correlation between AKI and heightened complication rates, poor functional outcome, extended hospital stays, and elevated mortality rates. Early detection of AKI in SAH patients is vital to enhance their chances of recovery.

Management of external ventricular drain: to wean or not to wean?

PURPOSE: External ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD. METHODS: This was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome. RESULTS: Out of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039). CONCLUSION: Gradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

Partial coil embolization before surgical clipping of ruptured intracranial aneurysms.

OBJECTIVE: Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR. METHODS: We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination. RESULTS: We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95-8.7] vs. 4.6 mm [3.3-6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4%, vs. 30/73, 41%; P = 0.001). Inpatient mortality was 14.8% (4/27) in patients with partially-embolized aneurysms and 28.8% (21/73) in patients without embolization (P = 0.20). Discharge to home or inpatient rehabilitation was 74.0% in patients with partially-embolized aneurysms and 56.2% in patients without embolization (P = 0.11). A complication from partial embolization occurred in 2/27 (7.4%) patients. CONCLUSIONS: Preoperative partial endovascular coil embolization of ruptured aneurysms is associated with a reduced frequency of IOR during definitive treatment with surgical clip obliteration. These results and the impact of preoperative partial endovascular coil embolization on functional outcomes should be confirmed with a randomized trial.

Association of hemoglobin drift and outcomes in patients with aneurysmal subarachnoid hemorrhage.

The relationship between in-hospital hemoglobin (Hb) drift and outcomes in patients undergoing surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH) is not well studied. This study aims to investigate the association between Hb drift and mortality in this patient population. We conducted a cohort study encompassing adult patients diagnosed with aSAH who were admitted to a university hospital. These patients were stratified into distinct groups based on their Hb drift levels. We employed logistic and Cox proportional hazard models to assess the relationship between Hb drift and outcomes. Additionally, propensity score matching (PSM) was utilized to ensure comparability between patient groups. The discriminative performance of different models was evaluated using C-statistics, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Overall, our cohort comprised 671 patients, of whom 165 (24.6%) demonstrated an in-hospital Hb drift exceeding 25%. The analyses revealed elevated Hb drift was independently associated with higher likelihood of follow-up mortality (aOR: 3.29, 95% CI: 1.65 to 6.56; P = 0.001) and in-hospital mortality (aOR: 3.44, 95% CI: 1.55 to 7.63; P = 0.002). PSM analysis yielded similar results. Additionally, patients with Hb drift exhibited a notable decrease in survival rate compared to those without Hb drift (aHR: 3.99, 95% CI 2.30 to 6.70; P < 0.001). Furthermore, the inclusion of Hb drift significantly improved the C-statistic (P = 0.037), IDI (2.78%; P = 0.004) and NRI metrics (41.86%; P < 0.001) for mortality prediction. In summary, our results highlight that an in-hospital Hb drift exceeding 25% serves as an independent predictor of mortality in patients who have undergone surgical clipping for aSAH.

ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway.

BACKGROUND: Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting BAP1 mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH. RESULTS: First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome-mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH. CONCLUSIONS: Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.

Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation.

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and ß-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.

Chiari malformation presenting with subarachnoid hemorrhage: a case report.

Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM. A menudo, las malformaciones de Chiari (CM) son diagnosticadas en los niños y los adultos jóvenes, y la incidencia en la populación adulto es solamente 0.77%. A veces, los pacientes con CM desarrollan una siringomielia y la hipertensión intracraneal debido a la obstrucción del líquido cefalorraquídeo y los cambios a los dinámicos del fluido a la unión craneocervical. Nosotros describimos el caso de una mujer de 65-años que presentó con una hemorragia subaracnoideo, que no apareció en el angiograma, y con un nuevo diagnóstico de CM 1 con una siringomielia. Después de nosotros excluimos cualquier aneurisma o malformación vascular, hicimos una craneotomía suboccipital para una descompresión de Chiari con una laminectomía de C1. No fue otras complicaciones con la cirugía y sus síntomas mejoraron. Este caso clínico recalca una presentación anormal de una CM.

Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA): study protocol for a randomized controlled trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.