The Prognostic Role of Peritumoral Edema in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis.

OBJECTIVE: Previous studies on glioblastomas (GBMs) have not reached a consensus on peritumoral edema (PTE)'s influence on survival. This study evaluated the PTE index's prognostic role in newly diagnosed GBMs using a well-designed method. METHODS: Selected patients were reviewed after a rigorous screening process. Their general information was obtained from electronic medical records. The imaging metrics (MTD, TTM, TTE) representing tumor diameter, laterality, and PTE extent were obtained by manual measurement in Syngo FastView software. The PTE index was a ratio of TTE to MTD. Multiple variables were evaluated using analysis of variance and Cox regression model. RESULTS: Of 143 patients, 62 were included in this study. MGMT promoter methylation and tumor laterality were both independent prognostic factors (p = 0.020, 0.042; HR = 0.272, 2.630). The lateral tumors' index was higher than that of the medial tumors (57.7% vs. 42.6%, p = 0.027). Low-index tumors were located in relatively medial positions compared with high-index tumors (TTM, 4.9 vs. 12.8, p = 0.032). This finding indicated that the PTE index tended to increase with tumor laterality. Moreover, the patients with low-index tumors had a significant survival disadvantage in the univariate analysis but not in the multivariate analysis (p = 0.023, 0.220). However, further analysis found that the combination of tumor laterality and PTE statistically stratified the survival outcome. The patients with lateral high-index tumors survived significantly longer (p = 0.022, HR = 1.927). CONCLUSIONS: In contrast with the previous studies, this study recommends combining PTE and tumor laterality for survival stratification in newly diagnosed GBMs.

Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke.

As swelling occurs, CSF is preferentially displaced from the ischemic hemisphere. The ratio of CSF volume in the stroke-affected hemisphere to that in the contralateral hemisphere may quantify the progression of cerebral edema. We automatically segmented CSF from 1,875 routine CTs performed within 96 hours of stroke onset in 924 participants of a stroke cohort study. In 737 subjects with follow-up imaging beyond 24-hours, edema severity was classified as affecting less than one-third of the hemisphere (CED-1), large hemispheric infarction (LHI, over one-third the hemisphere), without midline shift (CED-2) or with midline shift (CED-3). Malignant edema was LHI resulting in deterioration, requiring osmotic therapy, surgery, or resulting in death. Hemispheric CSF ratio was lower on baseline CT in those with LHI (0.91 vs. 0.97, p < 0.0001) and decreased more rapidly in those with LHI who developed midline shift (0.01 per hour for CED-3 vs. 0.004/hour CED-2). The ratio at 24-hours was lower in those with midline shift (0.41, IQR 0.30-0.57 vs. 0.66, 0.56-0.81 for CED-2). A ratio below 0.50 provided 90% sensitivity, 82% specificity for predicting malignant edema among those with LHI (AUC 0.91, 0.85-0.96). This suggests that the hemispheric CSF ratio may provide an accessible early biomarker of edema severity.

Effects of Hemodialysis on Prognosis in Individuals with Comorbid ERSD and ICH: A Retrospective Single-Center Study.

OBJECTIVES: End-stage renal disease (ESRD) is one of the most critical risk factors of intracerebral hemorrhage (ICH). We aimed to investigate the effects of maintenance hemodialysis on hematoma volume, edema volume, and prognosis in patients with comorbid ESRD and ICH. MATERIALS AND METHODS: Patients with comorbid ESRD and ICH were divided into two groups based on whether receiving maintenance hemodialysis. Hematoma and perihemorrhagic edema (PHE) volumes and relative edema ratio after admission were assessed on head computed tomography scans. RESULTS: During the initial diagnosis, the dialysis group had lower PHE volume (16.41 vs 35.90 mL, P = 0.010), total volume of hematoma and edema (31.58 vs 54.58 mL, P = 0.013), and relative edema ratio (0.57 vs 0.92, P = 0.033) than the non-dialysis group. In addition, the peak PHE volume (36.68 vs 84.30 mL, P < 0.001), peak total volume of hematoma and edema (53.45 vs 127.69 mL, P = 0.011), and peak relative edema ratio (1.12 vs 1.92, P = 0.001) within one week after onset were lower in the dialysis group than in the non-dialysis group. The dialysis group had a higher in-hospital mortality rate than the non-dialysis group (40% vs 10%, P = 0.007). At 1-year follow-up, the two groups had similar 1-year-mortality rates and modified Rankin Scale. CONCLUSIONS: Hemodialysis can prevent the enlargement of edema and reduce PHE volume shortly after onset. Although dialyzed patients had a higher in-hospital mortality rate, hemodialysis did not affect 1-year survival rate and functional neurologic scales.

Severe Acute Neurologic Involvement in Children With Hemolytic-Uremic Syndrome.

BACKGROUND AND OBJECTIVES: Acute severe neurologic involvement is the most threatening complication in children with hemolytic-uremic syndrome (HUS). Our primary study objectives were to describe the association between acute neurologic manifestations (ANMs) and in-hospital mortality among children with HUS. METHODS: Using the Pediatric Health Information System database, in this retrospective multicenter cohort study, we identified the first HUS-related inpatient visit among children ≤18 years (years 2004-2018). Frequency of selected ANMs and combinations of ANMs, as well as the rate of mortality, was calculated. Multivariate logistic regression was used to identify the association of ANMs and the risk of in-hospital mortality. RESULTS: Among 3915 patients included in the analysis, an ANM was noted in 10.4% (n = 409) patients. Encephalopathy was the most common ANM (n = 245). Mortality was significantly higher among patients with an ANM compared with patients without an ANM (13.9% vs 1.8%; P < .001). Individuals with any ANM had increased odds of mortality (odds ratio [OR]: 2.25; 95% confidence interval [CI]: 1.29-3.93; P = .004), with greater risk (OR: 2.60; 95% CI: 1.34-5.06; P = .005) among patients with ≥2 manifestations. Brain hemorrhage (OR: 3.09; 95% CI: 1.40-6.82; P = .005), brain infarction (OR: 2.64; 95% CI: 1.10-6.34; P = .03), anoxic brain injury (OR: 3.92; 95% CI: 1.49-10.31; P = .006), and brain edema (OR: 4.81; 95% CI: 1.82-12.71; P = .002) were independently associated with mortality. CONCLUSIONS: In this study, the largest systematic assessment of ANMs among children with HUS to date, we identify differences in in-hospital mortality based on the type of ANM, with increased risk observed for patients with multiple ANMs.

Altitude-Related Disorders on Mount Kilimanjaro, Tanzania: Two-Year Survey in a Local Referral Center.

INTRODUCTION: A significant number of climbers on Mount Kilimanjaro are affected by altitude-related disorders. The aim of this study was to determine the main causes of morbidity and mortality in a representative cohort of climbers based on local hospital records. METHODS: We conducted a 2-y retrospective chart review of all patients presenting to the main referral hospital in the region after a climb on Mount Kilimanjaro, including all relevant records and referrals for postmortem studies. RESULTS: We identified 62 climbers who presented to the hospital: 47 inpatients and 15 outpatients. Fifty-six presented with high altitude illness, which included acute mountain sickness (n=8; 14%), high altitude pulmonary edema (HAPE) (n=30; 54%), high altitude cerebral edema (HACE) (n=7; 12%), and combined HAPE/HACE (n=11; 20%). The mean altitude of symptom onset ranged from 4600±750 m for HAPE to 5000±430 m for HAPE/HACE. The vast majority of inpatients (n=41; 87%) were improved on discharge. Twenty-one deceased climbers, most having died while climbing (n=17; 81%), underwent postmortem evaluation. Causes of death were HAPE (n=16; 76%), HAPE/HACE (n=3; 14%), trauma (1), and cardiopulmonary (1). CONCLUSIONS: HAPE was the main cause of death during climbing as well as for hospital admissions. The vast majority of climbers who presented to hospital made a full recovery.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

Effect of Recanalization on Cerebral Edema, Long-Term Outcome, and Quality of Life in Patients with Large Hemispheric Infarctions.

OBJECTIVES: Space-occupying cerebral edema is the main cause of mortality and poor functional outcome in patients with large cerebral artery occlusion (LVO). We aimed to determine whether recanalization of LVO would augment cerebral edema volume and the impact on functional outcome and quality of life (QoL). MATERIALS AND METHODS: Prospectively, 43 patients with large middle cerebral artery territory infarction or NIHSS ≥ 12 on admission were enrolled. The degree of recanalization (partial and complete versus no recanalization) was assessed by computed tomography (CT)-angiography or Duplex ultrasound more than 24 h after symptom onset. Cerebral edema volume was measured on follow up CTs by computer-based planimetry. Mortality, functional outcome (by modified Ranking Scale (mRS) and Barthel Index (BI)) were assessed at discharge and 12 months, and QoL (by SF-36 and EQ-5D-3L) at 12 months. RESULTS: Mean cerebral edema volume was 333±141 ml without recanalization (n=13, group 1) and 276±140 ml with partial or complete recanalization (n=30, group 2, p= 0.23). There were no significant differences in mortality at discharge (38% versus 23%), at 12 months (58% versus 48%), in functional outcome at discharge (mRS 0-3: 0% both; mRS 4-5: 62% versus 77%) and at 12 months (mRS 0-3: 0% versus 11%; mRS 4-5: 42% versus 41%). The BI improved significantly from discharge to 12 months only in group 2 (p=0.001). Mean physical component score in SF-36 was 25.6±6.4, psychological component score was 41.9±14.1. In the EQ-5D-3L, most patients reported problems with activities of daily living, reduced mobility, and selfcare. CONCLUSIONS: Recanalization of a large cerebral artery occlusion in the anterior circulation territories is not associated with amplification of post-ischemic cerebral edema but may be correlated with better long-term functional outcome. QoL was low and mainly dependent on physical disability. The association between recanalization, collateral status and development of cerebral edema after LVO and the effect on functional outcome and quality of life should be explored in a larger patient population.

Amount of Brain Edema Correlates With Neurologic Recovery in Pediatric Cerebral Malaria.

BACKGROUND: Cerebral malaria (CM) remains a leading cause of mortality and morbidity in children in sub-Saharan Africa. Recent studies using brain magnetic resonance imaging have revealed increased brain volume as a major predictor of death. Similar morphometric predictors of morbidity at discharge are lacking. The aim of this study was to investigate the utility of serial cranial cisternal cerebrospinal fluid (CSF) volume measurements in predicting morbidity at discharge in pediatric CM survivors. METHODS: In this case-control study, 54 Malawian pediatric CM survivors with neurologic sequelae evident at discharge who underwent serial magnetic resonance imaging scans while comatose were matched to concurrently admitted children with serial imaging who made full recoveries. Serial cranial cisternal CSF volume quantified by radiologists blinded to outcome was evaluated as a predictor of neurologic deficits at discharge. The probability of neurologic sequelae was determined using a model that included coma duration and changes in cisternal CSF volume over time. RESULTS: Coma duration before admission was similar between cases and controls (16.1 vs. 15.3; P = 0.81), but overall coma was longer among children with sequelae (60 vs. 38 hours; P < 0.01). Lower initial CSF volumes and decreased volumes over time were both associated with a higher probability of neurologic sequelae at discharge. CONCLUSIONS: Among pediatric CM survivors with prolonged coma, lower initial CSF volume and decreasing volume during coma is associated with neurologic sequelae at discharge. These findings suggest that cerebral edema is an underlying contributor to both morbidity and mortality in pediatric CM.

External Validation and Modification of the EDEMA Score for Predicting Malignant Brain Edema After Acute Ischemic Stroke.

BACKGROUND: Accurate prediction of malignant brain edema (MBE) after stroke is paramount to facilitate close monitoring and timely surgical intervention. The Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score was useful to predict potentially lethal malignant edema in Western populations. We aimed to validate and modify it to achieve a better predictive value for MBE in Chinese patients. METHODS: Of ischemic stroke patients consecutively admitted in the Department of Neurology, West China Hospital between January 2010 and December 2017, we included patients with anterior circulation stroke, early signs of brain edema on computed tomography within 24 h of onset, and admission National Institutes of Health Stroke Scale (NIHSS) score ≥ 8. MBE was defined as the development of signs of herniation (including decrease in consciousness and/or anisocoria), accompanied by midline shift ≥ 5 mm on follow-up imaging. The EDEMA score consisted of five parameters: glucose, stroke history, reperfusion therapy, midline shift, and cistern effacement. We created a modified score by adding admission NIHSS score to the original EDEMA score. The discrimination of the score was assessed by the area under the receiver operating characteristics curve (AUC). Calibration was assessed by Hosmer-Lemeshow test and calibration plot. We compared the discrimination of the original and modified score by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Clinical usefulness of the two scores was compared by plotting net benefits at different threshold probabilities in the decision curve analysis. RESULTS: Of the 478 eligible patients (mean age 67.3 years; median NIHSS score 16), 93 (19%) developed MBE. The EDEMA score showed moderate discrimination (AUC 0.72, 95% confidence interval [CI] 0.67-0.76) and good calibration (Hosmer-Lemeshow test, P = 0.77). The modified score showed an improved discriminative ability (AUC 0.80, 95% CI 0.76-0.84, P < 0.001; NRI 0.67, 95% CI 0.55-0.78, P < 0.001; IDI 0.07, 95% CI 0.06-0.09, P < 0.001). Decision curves showed that the modified score had a higher net benefit than the original score in a range of threshold probabilities lower than 60%. CONCLUSIONS: The original EDEMA score showed an acceptable predictive value for MBE in Chinese patients. By adding the admission NIHSS score, the modified score allowed for a more accurate prediction and clinical usefulness. Further validation in large cohorts of different ethnicities is needed to confirm our findings.

Comparative analysis for the implication of serum cardiac troponin measurements by conventional versus high-sensitivity assays in patients with traumatic brain injury.

BACKGROUND: Stress-induced myocardial injury is not well-studied in patients with head injury. We aimed to assess the prognostic implication of positive (+ve) Troponins (Tn) measurements by conventional (cTnT) versus High-Sensitivity (HsTnT) assay in patients with traumatic brain injury (TBI). METHODS: A retrospective analysis was conducted for patients who were admitted with TBI. Patient demographics, clinical presentation, troponin assay results, TBI lesions, and hospital outcomes were analyzed and compared based on troponin assay (cTnT versus HsTnT). RESULTS: Across the study period, 654 patients with TBI had troponin levels measured within 24 h postinjury (cTnT=252 and HsTnT=402). The mean age was 31 years and 46% had positive troponins. There were 147 deaths (22.5%); of them 54% had +ve HsTnT, 23% had +ve cTnT, 16% had -ve cTnT and 7% had -ve HsTnT). When the troponins were tested ≤4 h postinjury, the mortality was 10.2% in patients with -ve cTnT and 4% in patients with -ve HsTnT. There was no documented obvious direct trauma to the heart. Overall, patients with positive troponins had lower Glasgow Coma Scale (GCS), higher Injury Severity Scores and higher rates of brain edema (P=0.001), pneumonia and sepsis (P=0.001) than those with negative troponin results. In two different models, multivariate regression analysis showed that +ve cTnT and +ve HsTnT were independent predictors of mortality (OR 4.02, 95% CI: 1.72-9.39) and (OR 4.31; 95% CI: 1.76-10.57); respectively, after adjusting for age, injury severity scores, GCS at ED, head AIS, pneumonia, ARDS, surgical interventions, and chest injury. CONCLUSIONS: Although the positivity of any troponin assay is associated with high mortality post-TBI, the use of HsTnT relatively outperforms the conventional troponin assay for early risk stratification and detection of stress-induced myocyte injury in patients with TBI.

Clinical Significance of Fractional Anisotropy Measured in Peritumoral Edema as a Biomarker of Overall Survival in Glioblastoma: Evidence Using Correspondence Analysis.

INTRODUCTION: Fractional anisotropy (FA), a diffusion tensor image (DTI) derived biomarker is related to invasion, infiltration, and extension of glioblastoma (GB). We aimed to evaluate FA values and their association with intervals of overall survival (OS). MATERIALS AND METHODS: Retrospective study conducted in 36 patients with GB included 23 (63.9%) males, 46 ± 14 y; and 13 (36.1%) females, 53 ± 13; followed up for 36 months. We measured FA at edema, enhancing rim, and necrosis. We created two categorical variables using levels of FA and intervals of OS to evaluate their relationships. Kaplan-Meier method and correspondence analysis evaluated the association between OS (grouped in 7 six-month intervals) and FA measurements. RESULTS: Median FA values were higher in healthy brain regions (0.351), followed by peritumoral edema (0.190), enhancing ring (0.116), and necrosis (0.071). Pair-wise comparisons among tumor regions showed a significant difference, P < 0.001. The median OS for all patients was 19.3 months; variations in the OS curves among subgroups was significant χ2 (3) = 8.48, P = 0.037. Correspondence analysis showed a significant association between FA values in the edema region and the survival intervals χ2 (18) = 30.996, P = 0.029. CONCLUSIONS: Alternative multivariate assessment using correspondence analysis might supplement the traditional survival analysis in patients with GB. A close follow-up of the variability of FA in the peritumoral edema region is predictive of the OS within specific six-month interval subgroup. Further studies should focus on predictive models combining surgical and DTI biomarkers.

Leakage of the blood-brain barrier followed by vasogenic edema as the ultimate cause of death induced by acute methamphetamine overdose.

Methamphetamine (METH) is a potent CNS stimulant that is widely used as a recreational drug. Due to its ability to increase bodily heat production and diminish heat loss due to peripheral vasoconstriction, METH is able to increase brain and body temperature. The hyperthermic effects of METH are potentiated when the drug is used under conditions of psycho-physiological activation and in warm ambient temperatures. In this short review, we present and discuss our data on the effects of METH on brain temperature and a number of neural parameters that characterize permeability of the blood-brain barrier (albumin immunoreactivity), glial activity (GFAP immunoreactivity), brain tissue water content, and structural abnormalities of brain cells. We demonstrate that the extent of these neural alterations strongly depends on METH-induced brain temperature elevation and they all dramatically increase following exposure to METH in warm (29°C) vs. standard (23°C) ambient temperatures. Based on these data we consider possible pathophysiological mechanisms underlying acute METH toxicity, suggesting the critical role of drug-induced brain hyperthermia, temperature-dependent leakage of the blood-brain barrier (BBB), and the development of vasogenic edema that could finally result in decompensation of vital functions and death.

Early prediction of neurological outcome after barbiturate coma therapy in patients undergoing brain tumor surgery.

After a difficult brain tumor surgery, refractory intracranial hypertension (RICH) may occur due to residual tumor or post-operative complications such as hemorrhage, infarction, and aggravated brain edema. We investigated which predictors are associated with prognosis when using barbiturate coma therapy (BCT) as a second-tier therapy to control RICH after brain tumor surgery. The study included adult patients who underwent BCT after brain tumor surgery between January 2010 and December 2016. The primary outcome was neurological status upon hospital discharge, which was assessed using the Glasgow Outcome Scale (GOS). In the study period, 4,296 patients underwent brain tumor surgery in total. Of these patients, BCT was performed in 73 patients (1.7%). Among these 73 patients, 56 (76.7%) survived to discharge and 25 (34.2%) showed favorable neurological outcomes (GOS scores of 4 and 5). Invasive monitoring of intracranial pressure (ICP) was performed in 60 (82.2%) patients, and revealed that the maximal ICP within 6 h after BCT was significantly lower in patients with favorable neurological outcome as well as in survivors (p = 0.008 and p = 0.028, respectively). Uncontrolled RICH (ICP ≥ 22 mm Hg within 6 h of BCT) was an important predictor of mortality after BCT (adjusted hazard ratio 12.91, 95% confidence interval [CI] 2.788-59.749), and in particular, ICP ≥ 15 mm Hg within 6 h of BCT was associated with poor neurological outcome (adjusted odds ratio 9.36, 95% CI 1.664-52.614). Therefore, early-controlled ICP after BCT was associated with clinical prognosis. There were no significant differences in the complications associated with BCT between the two neurological outcome groups. No BCT-induced death was observed. The active and timely control of RICH may be beneficial for clinical outcomes in patients with RICH after brain tumor surgery.

Progesterone Is More Effective Than Dexamethasone in Prolonging Overall Survival and Preserving Neurologic Function in Experimental Animals with Orthotopic Glioblastoma Allografts.

OBJECTIVE: Dexamethasone (DEXA) has been widely used in the management of peritumoral brain edema. DEXA, however, has many systemic side effects and can interact negatively with glioma therapy. Progesterone (PROG), however, is a well-tolerated and readily accessible anti-inflammatory and antiedema agent, with potent neuroprotective properties. We investigated whether PROG could serve as a viable alternative to DEXA in the management of peritumoral brain edema. METHODS: We used an orthotopic C6 glioblastoma model with male Sprague-Dawley rats. Tumor grafts were allowed to grow for 14 days before drug treatment with DEXA 1 mg/kg, PROG 10 mg/kg, or PROG 20 mg/kg for 5 consecutive days. The overall animal survival and neurologic function were evaluated. Mechanistic studies on blood-brain barrier permeability and angiogenic responses were performed on the ex vivo tumor grafts. RESULTS: We found that all drug treatments prolonged overall survival to different extents. PROG 10 mg led to significantly longer survival and better preservation of neurologic function and body weight. The blood-brain barrier permeability was better preserved with PROG 10 mg than with DEXA, possibly through downregulation of matrix metalloproteinase-9 and aquaporin-4 expression. Antiangiogenic responses were also observed in the PROG group. CONCLUSIONS: The present proof-of-concept pilot study has provided novel information on the use of PROG as a corticosteroid-sparing agent in brain tumor management. Further translational and clinical studies are warranted.

Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases.

BACKGROUND: Twenty percent of all brain metastases (BM) occur in the posterior fossa (PF). Radiotherapy sometimes associated with surgical resection remains the therapeutic option, while Karnovsky performance status and graded prognostic assessment (GPA) are the best preoperative survival prognostic factors. OBJECTIVE: To explore the prognostic role of peritumoral brain edema in the PF, which has never been explored though its role in supratentorial BM has been debated. METHODS: A total of 120 patients diagnosed with PF metastasis who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient medical files. The tumor volumes and their associated edema were calculated via manual delineation; subsequently the edema/tumor volume ratio was determined. RESULTS: In multivariate analysis with Cox multivariate proportional hazard model, the edema to tumor volumes ratio (hazard ratio [HR]: 1.727, 95% confidence interval [CI] 1.427-2.083; P < .0001) was identified as a new strong independent prognosis factor on overall survival (OS) whereas edema volume alone was not (P = .469). Moreover, BM complete resection (HR: 0.447, 95% CI 0.277-0.719; P < .001), low (0-1) World Health Organization status at diagnosis (HR: 2.109, 95% CI 1.481-3.015; P < .0001), high GPA class at diagnosis (HR: 1.77, 95% CI 0.9-2.9; P < .04), and postoperative brain irradiation (HR: 2.019, 95% CI 1.213-3.361; P < .007] were all confirmed as independent predictive factors for survival. CONCLUSION: The edema/tumor ratio appears to greatly influence OS in patients suffering from PF metastases unlike the extent of edema alone. This easily determined as well as strong prognostic factor could be used as an interesting tool in clinical practice to help the management of these patients.

Age-specific clinical characteristics and outcome in patients over 60 years old with large hemispheric infarction.

OBJECTIVE: We aimed to investigate age-specific clinical characteristics in patients aged >60 years with large hemispheric infarction (LHI). METHODS: We prospectively enrolled consecutive patients with LHI. Patients were divided into two groups: ≤60 vs. >60 years, and demographics, vascular risk factors, clinical feature, in-hospital treatment, 3-month mortality, and unfavorable outcome (defined as a mRS score of 4-6) rate were compared. RESULTS: Of the 256 cases included, 140 (54.7%) were older than 60 years. Compared with the younger, the older patients had higher rates of hypertension (66.4% vs. 31.0%), coronary heart disease (19.3% vs. 2.6%), atrial fibrillation (53.6% vs. 31.0%; all p < 0.001), more history of stroke (21.4% vs. 5.2%, p < 0.001), less history of rheumatic heart disease (16.4% vs. 30.1%, p = 0.009), and alcohol consumption (12.1% vs. 21.6%, p = 0.043). Cardio-embolism is the most common stroke etiology regardless of age (55.7% and 38.8%, respectively). Furthermore, the elderly less frequently received decompressive hemicraniectomy (4.3% vs. 15.5%, p = 0.005) and mechanical ventilation (7.9% vs. 16.4%, p = 0.035) and had a higher frequency of stroke-related complication (83.6% vs. 66.4%, p = 0.001). A total of 26 (18.6%) older patients and 15 (12.9%) younger patients died during hospitalization (p = 0.221), and 59 (42.1%) older patients and 35 (30.2%) younger patients died at 3 months (p = 0.061). Patient aged >60 years had significantly higher unfavorable outcome rate at 3 months (adjusted odds ratio, OR 4.30, 95% confidence interval [CI] 2.08-8.88; p < 0.05]. However, older age is not independently associated with 3-month mortality (42.1% vs. 30.2%, p = 0.095 [log-rank test]). CONCLUSIONS: Large hemispheric infarction patients over 60 years old were a little more than those aged ≤60 years and constitute more than half of those suffered from malignant brain edema and two thirds of in-hospital death and 3-month mortality. The elderly had more cardio-origin risk factors, received less aggressive hospital treatment, and showed higher risk of unfavorable outcome than the younger.

Effect of IV glyburide on adjudicated edema endpoints in the GAMES-RP Trial.

OBJECTIVE: In this secondary analysis of the Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial, we report the effect of IV glyburide on adjudicated, edema-related endpoints. METHODS: Blinded adjudicators assigned designations for hemorrhagic transformation, neurologic deterioration, malignant edema, and edema-related death to patients from the GAMES-RP phase II randomized controlled trial of IV glyburide for large hemispheric infarct. Rates of these endpoints were compared between treatment arms in the per-protocol sample. In those participants with malignant edema, the effects of treatment on additional markers of edema and clinical deterioration were examined. RESULTS: In the per-protocol sample, 41 patients received glyburide and 36 received placebo. There was no difference in the frequency of hemorrhagic transformation (n = 24 [58.5%] in IV glyburide vs n = 23 [63.9%] in placebo, p = 0.91) or the incidence of malignant edema (n = 19 [46%] in IV glyburide vs n = 17 [47%] in placebo, p = 0.94). However, treatment with IV glyburide was associated with a reduced proportion of deaths attributed to cerebral edema (n = 1 [2.4%] with IV glyburide vs n = 8 [22.2%] with placebo, p = 0.01). In the subset of patients with malignant edema, those treated with IV glyburide had less midline shift (p < 0.01) and reduced MMP-9 (matrix metalloproteinase 9) levels (p < 0.01). The glyburide treatment group had lower rate of NIH Stroke Scale (NIHSS) increase of ≥4 during the infusion period (n = 7 [37%] in IV glyburide vs n = 12 [71%] in placebo, p = 0.043), and of change in level of alertness (NIHSS subscore 1a; n = 11 [58%] vs n = 15 [94%], p = 0.016). CONCLUSION: IV glyburide was associated with improvements in midline shift, level of alertness, and NIHSS, and there were fewer deaths attributed to edema. Additional studies of IV glyburide in large hemispheric infarction are warranted to corroborate these findings. CLINICALTRIALSGOV IDENTIFIER: NCT01794182. LEVEL OF EVIDENCE: This study provides Class II evidence that for patients with large hemispheric infarction, IV glyburide improves some edema-related endpoints.

Low-chloride versus high-chloride hypertonic solution for the treatment of subarachnoid hemorrhage-related complications (The ACETatE trial): study protocol for a pilot randomized controlled trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI. METHODS: A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl- concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl- concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia. DISCUSSION: In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl- content on serum Cl- concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl- concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017.

Treatment with Mannitol is Associated with Increased Risk for In-Hospital Mortality in Patients with Acute Ischemic Stroke and Cerebral Edema.

BACKGROUND: Current guidelines state that osmotic therapy is reasonable in patients with clinical deterioration from cerebral infarction-related cerebral edema. However, there are limited data on the safety and efficacy of this therapy. We aimed to evaluate the effect of mannitol on the outcome of ischemic stroke-related cerebral edema. METHODS AND RESULTS: We prospectively studied 922 consecutive patients admitted with acute ischemic stroke. Patients who showed space-occupying brain edema with tissue shifts compressing the midline structures received mannitol. The outcome was assessed with dependency rates at discharge (modified Rankin Scale grade 2-5) and in-hospital mortality. Rates of dependency were higher in patients treated with mannitol (n = 86) than in those who were not (97.7 and 58.5%, respectively; p < 0.001). Independent predictors of dependency were age, history of ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) score at admission. Rates of mortality were higher in patients treated with mannitol than in those who were not (46.5 and 5.6%, respectively; p < 0.001). Independent predictors of in-hospital mortality were diastolic blood pressure [relative risk (RR) 1.05, 95% confidence interval (CI) 1.02-1.08, p < 0.001], NIHSS score at admission (RR 1.19, 95% CI 1.14-1.23, p < 0.001) and treatment with mannitol (RR 3.45, 95% CI 1.55-7.69, p < 0.005). CONCLUSIONS: Administration of mannitol to patients with ischemic stroke-related cerebral edema does not appear to affect the functional outcome and might increase mortality, independently of stroke severity.