Perifocal edema is a risk factor for preoperative seizures in patients with meningioma WHO grade 2 and 3.

BACKGROUND: Patients with intracranial meningiomas frequently suffer from tumor-related seizures prior to resection, impacting patients' quality of life. We aimed to elaborate on incidence and predictors for seizures in a patient cohort with meningiomas WHO grade 2 and 3. METHODS: We retrospectively searched for patients with meningioma WHO grade 2 and 3 according to the 2021 WHO classification undergoing tumor resection. Clinical, histopathological and imaging findings were collected and correlated with preoperative seizure development. Tumor and edema volumes were quantified. RESULTS: Ninety-five patients with a mean age of 59.5 ± 16.0 years were included. Most tumors (86/95, 90.5%) were classified as atypical meningioma WHO grade 2. Nine of 95 tumors (9.5%) corresponded to anaplastic meningiomas WHO grade 3, including six patients harboring TERT promoter mutations. Meningiomas were most frequently located at the convexity in 38/95 patients (40.0%). Twenty-eight of 95 patients (29.5%) experienced preoperative seizures. Peritumoral edema was detected in 62/95 patients (65.3%) with a median volume of 9 cm3 (IR: 0-54 cm3). Presence of peritumoral edema but not age, tumor localization, TERT promoter mutation, brain invasion or WHO grading was associated with incidence of preoperative seizures, as confirmed in multivariate analysis (OR: 6.61, 95% CI: 1.18, 58.12, p = *0.049). Postoperative freedom of seizures was achieved in 91/95 patients (95.8%). CONCLUSIONS: Preoperative seizures were frequently encountered in about every third patient with meningioma WHO grade 2 or 3. Patients presenting with peritumoral edema on preoperative imaging are at particular risk for developing tumor-related seizures. Tumor resection was highly effective in achieving seizure freedom.

Progesterone induces neuroprotection associated with immune/inflammatory modulation in experimental traumatic brain injury.

An imbalance of immune/inflammatory reactions aggravates secondary brain injury after traumatic brain injury (TBI) and can deteriorate clinical prognosis. So far, not enough therapeutic avenues have been found to prevent such an imbalance in the clinical setting. Progesterone has been shown to regulate immune/inflammatory reactions in many diseases and conveys a potential protective role in TBI. This study was designed to investigate the neuroprotective effects of progesterone associated with immune/inflammatory modulation in experimental TBI. A TBI model in adult male C57BL/6J mice was created using a controlled contusion instrument. After injury, the mice received consecutive progesterone therapy (8 mg/kg per day, i.p.) until euthanized. Neurological deficits were assessed via Morris water maze test. Brain edema was measured via the dry-wet weight method. Immunohistochemical staining and flow cytometry were used to examine the numbers of immune/inflammatory cells, including IBA-1 + microglia, myeloperoxidase + neutrophils, and regulatory T cells (Tregs). ELISA was used to detect the concentrations of IL-1ß, TNF-α, IL-10, and TGF-ß. Our data showed that progesterone therapy significantly improved neurological deficits and brain edema in experimental TBI, remarkably increased regulatory T cell numbers in the spleen, and dramatically reduced the activation and infiltration of inflammatory cells (microglia and neutrophils) in injured brain tissue. In addition, progesterone therapy decreased the expression of the pro-inflammatory cytokines IL-1ß and TNF-α but increased the expression of the anti-inflammatory cytokine IL-10 after TBI. These findings suggest that progesterone administration could be used to regulate immune/inflammatory reactions and improve outcomes in TBI.

Hepatic veno-occlusive disease complicated with extreme hyperammonaemia (920 µmol/L) treated with defibrotide, lactulose, rifampin and haemodialysis.

Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS) is a severe complication that can occur following haematopoietic stem cell transplant (HSCT) with high-intensity conditioning chemotherapy regimens. Severe VOD/SOS, often characterised by multiorgan failure, is associated with a high mortality rate. This case report details the complex clinical course of a male patient in his mid-20s, recently diagnosed with B cell acute lymphoblastic leukaemia, who underwent allogeneic HSCT. Based on the 2023 European Society for Blood and Marrow Transplantation (EBMT) criteria, the patient developed very severe VOD/SOS, prompting immediate treatment with defibrotide. Unexpectedly, he developed profound hyperammonaemia exceeding 900 µmol/L, leading to encephalopathy and cerebral oedema. Despite aggressive interventions including defibrotide, lactulose, rifampin and haemodialysis, the patient passed away due to cerebral oedema and pulseless electrical activity arrest. We theorise the hyperammonaemia is disproportionate to his hepatic dysfunction and is possibly secondary to an acquired defect of the urea synthesis consistent with idiopathic hyperammonaemia, a rare complication in patients receiving intense conditioning chemotherapy.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

BACKGROUND: Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. METHODS: The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. RESULTS: Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. CONCLUSIONS: In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

External validation and comparison of MBE, EDEMA, and modified EDEMA scores for predicting malignant cerebral EDEMA in Chinese patients with large hemispheric infarction patients without revascularization.

BACKGROUND: Malignant cerebral edema (MCE) is a severe condition characterized by rapid neurological deterioration and a potentially poor prognosis. Scoring systems including the malignant brain edema (MBE) score, Enhanced Detection of Edema in Malignant Anterior Circulation Stroke score (EDEMA), and modified EDEMA score, have been developed to predict MCE in patients with large hemispheric infarction (LHI). We aimed to externally validate and comparethe predictive efficacy of these scores in LHI patients within 48 h of onset and not undergoing reperfusion therapy. METHODS: Demographic, clinical and radiological data were retrospectively collected from LHI patients within 48 h of onset and not receiving reperfusion therapy. Patients were divided into MCE and non-MCE group. The calibration, discrimination, and clinical practicability of the three scores were verified using Hosmer-Lemeshow goodness-of-fit test, receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Finally, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were applied to determine the discrimination performance of the three scores. RESULTS: A total of 314 patients were included in the study, with 122 cases being MCE patients. The Hosmer-Lemeshow goodness-of-fit test showed excellent fitting ability across the MBE (p = 0.36), EDEMA (p = 0.61), and modified EDEMA scores (p = 0.62) in our patients. The MBE, EDEMA, and modified EDEMA scores had the AUCs of 0.855 (95 % CI 0.818-0.898), 0.782 (95 % CI 0.727-0.837) and 0.878 (95 % CI 0.844-0.919) respectively. The MBE (NRI, 0.33; 95 % CI, 0.11-0.56, p = 0.003 and IDI, 0.11; 95 % CI, 0.03-0.18; p = 0.004) and modified EDEMA scores (NRI, 1.10; 95 % CI, 0.94-1.26; p < 0.001 and IDI, 0.17; 95 % CI, 0.13-0.20, p < 0.001) showed better performance than the EDEMA score. DCA demonstrated that the modified EDEMA score outperformed the other two scores, possessing heightened clinical usefulness. CONCLUSIONS: The MBE, EDEMA, and modified EDEMA scores for predicting MCE are also applicable in non-revascularization LHI patients within 48 h of onset. Both the MBE and modified EDEMA scores demonstrated higher predictive validity as predictive tools for MCE in LHI patients than the EDEMA score. Furthermore, the modified EDEMA score could be a suitable prediction tool in Chinese patients for its excellent clinical utility.

Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

Quantification of ischemic brain edema after mechanical thrombectomy using dual-energy computed tomography in patients with ischemic stroke.

Net water uptake (NWU) is a quantitative imaging biomarker used to assess cerebral edema resulting from ischemia via Computed Tomography (CT)-densitometry. It serves as a strong predictor of clinical outcome. Nevertheless, NWU measurements on follow-up CT scans after mechanical thrombectomy (MT) can be affected by contrast staining. To improve the accuracy of edema estimation, virtual non-contrast images (VNC-I) from dual-energy CT scans (DECT) were compared to conventional polychromatic CT images (CP-I) in this study. We examined NWU measurements derived from VNC-I and CP-I to assess their agreement and predictive value in clinical outcome. 88 consecutive patients who received DECT as follow-up after MT were included. NWU was quantified on CP-I (cNWU) and VNC-I (vNWU). The clinical endpoint was functional independence at discharge. cNWU and vNWU were highly correlated (r = 0.71, p < 0.0001). The median difference between cNWU and vNWU was 8.7% (IQR: 4.5-14.1%), associated with successful vessel recanalization (mTICI2b-3) (ß: 11.6%, 95% CI 2.9-23.0%, p = 0.04), and age (ß: 4.2%, 95% CI 1.3-7.0%, p = 0.005). The diagnostic accuracy to classify outcome between cNWU and vNWU was similar (AUC:0.78 versus 0.77). Although there was an 8.7% median difference, indicating potential edema underestimation on CP-I, it did not have short-term clinical implications.

Association between quantitative analysis of cerebral edema using CT imaging and neurological outcomes in cardiac arrest survivors.

BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.

Activation of the melanocortin-1 receptor attenuates neuronal apoptosis after traumatic brain injury by upregulating Merlin expression.

Traumatic brain injury (TBI) is a common disease worldwide with high mortality and disability rates. Besides the primary mechanical injury, the secondary injury associated with TBI can also induce numerous pathological changes, such as brain edema, nerve apoptosis, and neuroinflammation, which further aggravates neurological dysfunction and even causes the death due to the primary injury. Among them, neuronal apoptosis is a key link in the injury. Melanocortin-1 receptor (MC1R) is a G protein coupled receptor, belonging to the melanocortin receptor family. Studies have shown that activation of MC1R inhibits oxidative stress and apoptosis, and confers neuroprotective effects against various neurological diseases. Merlin is a protein product of the NF2 gene, which is widely expressed in the central nervous system (CNS) of mice, rats, and humans. Studies have indicated that Merlin is associated with MC1R. In this study, we explored the anti-apoptotic effects and potential mechanisms of MC1R. A rat model of TBI was established through controlled cortical impact. The MC1R-specific agonist Nle4-D-Phe7-α-Melanocyte (NDP-MSH) and the inhibitor MSG-606 were employed to explore the effects of MC1R and Merlin following TBI and investigated the associated mechanisms. The results showed that the expression levels of MC1R and Merlin were upregulated after TBI, and activation of MC1R promoted Merlin expression. Further, we found that MC1R activation significantly improved neurological dysfunction and reduced brain edema and neuronal apoptosis induced by TBI in rats. Mechanistically, its neuroprotective function and anti-apoptotic were partly associated with MC1R activation. In conclusion, we demonstrated that MC1R activation after TBI may inhibit apoptosis and confer neuroprotection by upregulating the expression of Merlin.

High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Inhibiting RIPK1-driven neuroinflammation and neuronal apoptosis mitigates brain injury following experimental subarachnoid hemorrhage.

RIPK1, a receptor-interacting serine/threonine protein kinase, plays a crucial role in maintaining cellular and tissue homeostasis by integrating inflammatory responses and cell death signaling pathways including apoptosis and necroptosis, which have been implicated in diverse physiological and pathological processes. Suppression of RIPK1 activation is a promising strategy for restraining the pathological progression of many human diseases. Neuroinflammation and neuronal apoptosis are two pivotal factors in the pathogenesis of brain injury following subarachnoid hemorrhage (SAH). In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as marked by the phosphorylation of RIPK1 at serine 166. The upregulation of p-RIPK1(S166) resulted in a significant augmentation of inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1α, CCL2, and CCL5, as well as neuronal apoptosis. The activation of RIPK1 in microglia and neurons following SAH could be effectively suppressed by administration of Nec-1 s, a specific inhibitor of RIPK1. Consequently, inhibition of RIPK1 resulted in a downregulation of inflammatory cytokines and chemokines and attenuation of neuronal apoptosis after SAH in vitro. Furthermore, the administration of Nec-1 s effectively mitigated neuroinflammation, neuronal apoptosis, brain edema, and neurobehavioral deficits in mice following SAH. Our findings suggest that inhibiting RIPK1 kinase represents a promising therapeutic strategy for mitigating brain injury after SAH by attenuating RIPK1-driven neuroinflammation and neuronal apoptosis.

Drug Discovery Research for Traumatic Brain Injury Focused on Functional Molecules in Astrocytes.

Traumatic brain injury (TBI) is severe damage to the head caused by traffic accidents, falls, and sports. Because TBI-induced disruption of the blood-brain barrier (BBB) causes brain edema and neuroinflammation, which are major causes of death or serious disabilities, protection and recovery of BBB function may be beneficial therapeutic strategies for TBI. Astrocytes are key components of BBB integrity, and astrocyte-derived bioactive factors promote and suppress BBB disruption in TBI. Therefore, the regulation of astrocyte function is essential for BBB protection. In the injured cerebrum of TBI model mice, we found that the endothelin ETB receptor, histamine H2 receptor, and transient receptor potential vanilloid 4 (TRPV4) were predominantly expressed in reactive astrocytes. We also showed that repeated administration of an ETB receptor antagonist, H2 receptor agonist, and TRPV4 antagonist alleviated BBB disruption and brain edema in a TBI mouse model. Furthermore, these drugs decreased the expression levels of astrocyte-derived factors promoting BBB disruption and increased the expression levels of astrocyte-derived protective factors in the injured cerebrum after TBI. These results suggest that the ETB receptor, H2 receptor, and TRPV4 are molecules that regulate astrocyte function, and might be attractive candidates for the development of therapeutic drugs for TBI.

CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke.

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

Adult Cerebral Malaria: Acute and Subacute Imaging Findings, Long-term Clinical Consequences.

Cerebral malaria is an important cause of mortality and neurodisability in endemic regions. We show magnetic resonance imaging (MRI) features suggestive of cytotoxic and vasogenic cerebral edema followed by microhemorrhages in 2 adult UK cases, comparing them with an Indian cohort. Long-term follow-up images correlate ongoing changes with residual functional impairment.

Simple approach to quantify hypoxic-ischemic brain injury severity from computed tomography imaging files after cardiac arrest.

BACKGROUND: Grey-white ratio (GWR) can estimate severity of cytotoxic cerebral edema secondary to hypoxic-ischemic brain injury after cardiac arrest and predict progression to death by neurologic criteria (DNC). Current approaches to calculating GWR are not standardized and have variable interrater reliability. We tested if measures of variance of brain density on early computed tomographic (CT) imaging after cardiac arrest could predict DNC. METHODS: We performed a retrospective cohort study, identifying post-arrest patients treated between 2011 and 2020 at our single center. We extracted demographic data from our registry and Digital Imaging and Communication in Medicine (DICOM) files for each patient's first brain CT. We analyzed slices 15-20 of each DICOM, corresponding to the level of the basal ganglia while accommodating differences in patient anatomy. We extracted pixel arrays and converted the radiodensities to Hounsfield units (HU). To focus on brain tissue densities, we excluded HU > 60 and < 10. We calculated the variance of each patient's HU distribution and the difference between the means of a two-group Gaussian finite mixture model. We compared these novel metrics to existing measures of cerebral edema, then randomly divided our data into 80% training and 20% test sets and used logistic regression to predict DNC. RESULTS: Of 1,133 included subjects, 457 (40%) were female, mean (standard deviation) age was 58 (16) years, and 115 (10%) progressed to DNC. CTs were obtained a median [interquartile range] of 4.2 [2.8-5.7] hours post-arrest. Our novel measures correlated weakly with GWR. HU variance, but not difference between mixture model means, differed significantly between subjects with and without sulcal or cistern effacement. GWR outperformed our novel measures in predicting progression to DNC with an area under the receiver operating characteristic curve (AUC) of 0.82, compared to HU variance (AUC = 0.73) and the difference between mixture model means (AUC = 0.56). CONCLUSION: There are differences in the distribution of HU on post-arrest CT in patients with qualitative measures of cerebral edema. Current methods to quantify cerebral edema outperform simple measures of attenuation variance on early brain CT. Further analyses could investigate if these measures of variance, or other distributional characteristics of brain density, have improved predictive performance on brain CTs obtained later in the clinical course or derived from discrete regions of anatomical interest.

Bevacizumab in the Treatment of Refractory Brain Edema in High-grade Glioma.

We report the case of a 14-year-old boy with a steroid-dependent refractory tumor whose longstanding dexamethasone treatment was successfully discontinued after a course of bevacizumab. The use of bevacizumab despite the absence of clear evidence of radionecrosis allowed a significant decrease in the amount of the brain edema.

Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.

Cerebral vasogenic edema, a severe complication of ischemic stroke, aggravates neurological deficits. However, therapeutics to reduce cerebral edema still represent a significant unmet medical need. Brain microvascular endothelial cells (BMECs), vital for maintaining the blood-brain barrier (BBB), represent the first defense barrier for vasogenic edema. Here, we analyzed the proteomic profiles of the cultured mouse BMECs during oxygen-glucose deprivation and reperfusion (OGD/R). Besides the extensively altered cytoskeletal proteins, ephrin type-A receptor 4 (EphA4) expressions and its activated phosphorylated form p-EphA4 were significantly increased. Blocking EphA4 using EphA4-Fc, a specific and well-tolerated inhibitor shown in our ongoing human phase I trial, effectively reduced OGD/R-induced BMECs contraction and tight junction damage. EphA4-Fc did not protect OGD/R-induced neuronal and astrocytic death. However, administration of EphA4-Fc, before or after the onset of transient middle cerebral artery occlusion (tMCAO), reduced brain edema by about 50%, leading to improved neurological function recovery. The BBB permeability test also confirmed that cerebral BBB integrity was well maintained in tMCAO brains treated with EphA4-Fc. Therefore, EphA4 was critical in signaling BMECs-mediated BBB breakdown and vasogenic edema during cerebral ischemia. EphA4-Fc is promising for the treatment of clinical post-stroke edema.

Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.

BACKGROUND AND OBJECTIVES: Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. METHODS: Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm 3 ), medium (10-50 cm 3 ), and large (>50 cm 3 ). RESULTS: The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm 3 and 27.3 cm 3 ; large PTBE volume correlated with poor preoperative KPS status ( P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. CONCLUSION: Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.

Analysis of brain edema in RHAPSODY.

BACKGROUND: Cerebral edema is a secondary complication of acute ischemic stroke, but its time course and imaging markers are not fully understood. Recently, net water uptake (NWU) has been proposed as a novel marker of edema. AIMS: Studying the RHAPSODY trial cohort, we sought to characterize the time course of edema and test the hypothesis that NWU provides distinct information when added to traditional markers of cerebral edema after stroke by examining its association with other markers. METHODS: A total of 65 patients had measurable supratentorial ischemic lesions. Patients underwent head computed tomography (CT), brain magnetic resonance imaging (MRI) scans, or both at the baseline visit and after 2, 7, 30, and 90 days following enrollment. CT and MRI scans were used to measure four imaging markers of edema: midline shift (MLS), hemisphere volume ratio (HVR), cerebrospinal fluid (CSF) volume, and NWU using semi-quantitative threshold analysis. Trajectories of the markers were summarized, as available. Correlations of the markers of edema were computed and the markers compared by clinical outcome. Regression models were used to examine the effect of 3K3A-activated protein C (APC) treatment. RESULTS: Two measures of mass effect, MLS and HVR, could be measured on all imaging modalities, and had values available across all time points. Accordingly, mass effect reached a maximum level by day 7, normalized by day 30, and then reversed by day 90 for both measures. In the first 2 days after stroke, the change in CSF volume was associated with MLS (ρ = -0.57, p = 0.0001) and HVR (ρ = -0.66, p < 0.0001). In contrast, the change in NWU was not associated with the other imaging markers (all p ⩾ 0.49). While being directionally consistent, we did not observe a difference in the edema markers by clinical outcome. In addition, baseline stroke volume was associated with all markers (MLS (p < 0.001), HVR (p < 0.001), change in CSF volume (p = 0.003)) with the exception of NWU (p = 0.5). Exploratory analysis did not reveal a difference in cerebral edema markers by treatment arm. CONCLUSIONS: Existing cerebral edema imaging markers potentially describe two distinct processes, including lesional water concentration (i.e. NWU) and mass effect (MLS, HVR, and CSF volume). These two types of imaging markers may represent distinct aspects of cerebral edema, which could be useful for future trials targeting this process.