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[Display omitted] • This paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH. • Microglia can interact with a wide range of cells, which is important for both disease development and treatment. • We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend. The inflammatory mechanism of intracerebral hemorrhage (ICH) has been widely studied, and it is believed that the regulation of this mechanism is of great significance to the prognosis. In the early stage of the acute phase of ICH, the release of a large number of inflammatory factors around the hematoma can recruit more inflammatory cells to infiltrate the area, further release inflammatory factors, cause an inflammatory cascade reaction, aggravate the volume of cerebral hematoma and edema and further destroy the blood–brain barrier (BBB), according to this, the crosstalk between cells may be of great significance in secondary brain injury (SBI). Because most of the cells recruited are inflammatory immune cells, this paper mainly discusses the cells based on the inflammatory mechanism to discuss their functions after ICH, we found that among the main cells inherent in the brain, glial cells account for the majority, of which microglia are the most widely studied and it can interact with a variety of cells, which is reflected in the literature researches on its pathogenesis and treatment. We believe that exploring multi-mechanism and multi-cell regulated drugs may be the future development trend, and the existing research, the comparison and unification of modeling methods, and the observation of long-term efficacy may be the first problem that researchers need to solve. [ABSTRACT FROM AUTHOR]

Recently, different groups have reported a rare, unexplained complication of sudden death with massive cerebral oedema immediately after cranioplasty. Case presentation: A 34-year-old woman underwent decompressive hemicraniectomy after traumatic brain injury. She was reportedly on oral contraceptives. She developed massive cerebral swelling immediately after an uneventful cranioplasty. After surgery, her pupils became fixed and dilated, and brain MRI revealed massive brain oedema. Magnetic resonance venography displayed occlusion in the deep venous sinus. The oedema was believed to be caused by venous sinus thrombosis. The patient's family declined to avail any surgical and medical treatment, and the patient died on the second postoperative day. Conclusions: Fatal massive cerebral oedema is an uncommon complication after cranioplasty in patients who had previously undergone decompressive craniectomy. Our patient was using oral contraceptives and was thus susceptible to the development of venous sinus thrombosis. Neurosurgeons must be aware of the complications associated with venous sinus thrombosis and discuss it with the patients and their families. [ABSTRACT FROM AUTHOR]

Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice. [ABSTRACT FROM AUTHOR]

Organ transplantation after brain death (BD) of the donor has been promoted in many countries as an established medical treatment. However, some problems with brain-dead organ transplantation have been reported. For example, there is no evidence as to the optimal observation period for a diagnosis and no evidence to support the interpretation of the various body movements observed after the determination of BD. A previously healthy 17-month-old girl with severe febrile convulsive status was transferred to our intensive care unit. The convulsions were refractory and the patient required respiratory management due to whole brain edema on head CT. Later she was diagnosed with acute encephalopathy. The patient showed a flat EEG, no responses on auditory brainstem responses (ABR), and loss of brainstem reflexes on repeated daily examinations. No apnea test was performed. Based on the diagnosis of clinical BD, coordinator of Japan Organ Transplant Network explained about organ donation on the 17th day of the disease. Subsequently, the family responded that they could not consent to organ donation, and the patient did not proceed to the legal BD determination. Around five weeks after the onset, spontaneous body movements began to appear, as not only the spinal reflexes but also the brainstem involvement. The pathophysiology of acute encephalopathy is largely unknown, and it is difficult to determine the observation period necessary for BD determination. What we have learned from this case is that clinical BD remains ambiguous and cannot be confirmed even with a thorough neurological examination, EEG, and ABR. [ABSTRACT FROM AUTHOR]

Introduction: Brain abscesses caused by Nocardia farcinica pathogen are rare and usually present as large abscesses with a thick and irregular wall. We present a case of a patient with signs and symptoms of central nervous system infection and had a fulminant evolution with malign cerebral oedema and death. Case report: The 35-year-old patient presented with mild symptoms that appeared 2 weeks prior and became more aggressive in the last 48 hours. After the initial examination and blood tests, the patient was suspected of a systemic infection because of the high white cell count and high level of inflammatory markers. Antibiotic therapy was started with Ciprofloxacin and Amoxicillin/Clavulanic Acid. The brain MRI showed a multinodular lesion in the right hemisphere, with contrast enhancement and central high diffusion restriction on T1, T2 and FLAIR. During the antibiotic treatment, the patient suddenly became comatose. Urgent brain CT scan showed malign cerebral oedema with brain shift. Discussion: There are 58 documented cases of Nocardia farcinica in the literature, as shown in a recent systematic review. Most of the cases are with immunocompromised patients, either through disease or secondary to treatment after organ transplant. In our case, we suspected immunodeficiencies based on the anamnestic data offered by the patient's family. Mortality rates are between 19% and 36,7% in all reported cases, but in our presented case the patient had a rapid aggressive evolution with malign brain oedema that resulted in death. Conclusions. The management of these cases requires urgent diagnostics and treatment. For our team, the first reported case of Nocardia farcinica and the fast aggressive evolution resulted in a negative outcome, even with antibiotics treatment and surgical evacuation of the abscess. [ABSTRACT FROM AUTHOR]

Ischemic stroke leads to hypoxia-induced neuronal death and behavioral abnormity, and is a major cause of death in the modern society. However, the treatments of this disease are limited. Brilliant Blue FCF (BBF) is an edible pigment used in the food industry that with multiple aromatic rings and sulfonic acid groups in its structure. BBF and its derivatives were proved to cross the blood-brain barrier and have advantages on the therapy of neuropsychiatric diseases. In this study, BBF, but not its derivatives, significantly ameliorated chemical hypoxia-induced cell death in HT22 hippocampal neuronal cell line. Moreover, protective effects of BBF were attributed to the inhibition of the extracellular regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK3β) pathways as evidenced by Western blotting analysis and specific inhibitors. Furthermore, BBF significantly reduced neurological and behavioral abnormity, and decreased brain infarct volume and cerebral edema induced by middle cerebral artery occlusion/reperfusion (MCAO) in rats. MCAO-induced increase of p-ERK in ischemic penumbra was reduced by BBF in rats. These results suggested that BBF prevented chemical hypoxia-induced otoxicity and MCAO-induced behavioral abnormity via the inhibition of the ERK and GSK3β pathways, indicating the potential use of BBF for treating ischemic stroke [ABSTRACT FROM AUTHOR]

Background: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment. Methods: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention. Results: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th–75th interquartile range 22.5–30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4). Conclusions: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of death and disability worldwide. Several mechanisms are involved in the pathogenesis of ischemic stroke (IS). The contributory role of the inflammatory and immunity processes was demonstrated both in vitro and in animal models, and was confirmed in humans. IS evokes an immediate inflammatory response that involves complex cellular and molecular mechanisms. All components of the innate and adaptive immunity systems are involved in several steps of the ischemic cascade. In the early phase, inflammatory and immune mechanisms contribute to the brain tissue damage, whereas, in the late phase, they participate to the tissue repair processes. In particular, damage-associated molecular patterns (DAMPs) appear critical for the promotion of altered blood brain barrier permeability, leukocytes infiltration, tissue edema and brain injury. Conversely, the activation of regulatory T lymphocytes (Tregs) plays protective effects. The identification of specific cellular/molecular elements belonging to the inflammatory and immune responses, contributing to the brain ischemic injury and tissue remodeling, offers the advantage to design adequate therapeutic strategies. In this article, we will present an overview of the knowledge on inflammatory and immunity processes in IS, with a particular focus on the role of DAMPs and leukocytes infiltration. We will discuss evidence obtained in preclinical models of IS and in humans. The main molecular mechanisms useful for the development of novel therapeutic approaches will be highlighted. The translation of experimental findings to the human disease is still a difficult step to pursue. Further investigations are required to fill up the existing gaps. [ABSTRACT FROM AUTHOR]

Objectives: Up to 10% of acute ischemic stroke (AIS) patients can die in the first 30 days. Older age and a higher National Institutes of Health Stroke Scale (NIHSS) score are associated with transition to comfort measures only (CMO) in AIS. There are insufficient data on specific stroke etiology, infarct location, or vascular territory for the association of AIS with the use of CMO. We therefore evaluated the clinical and imaging factors associated with utilization of CMO and their outcomes. Methods: AIS patients seen in an academic comprehensive stroke center in the United States between July 1, 2015, and June 30, 2016, were subgrouped based on the use of CMO orders (CMO vs. non-CMO) during hospitalization. Clinical, laboratory, and imaging data were analyzed. Multivariable logistic regression analysis was performed, adjusting for pertinent covariates. Results: The study consisted of 296 patients, 27 (9%) patients were transitioned to CMO. Compared with non-CMO patients, those with CMO were older (mean ± standard deviation: 66 ± 15 vs. 75 ± 11 years, p = 0.002). Hemorrhagic transformation of AIS was more likely in CMO (17% vs. 41%, p = 0.0030) compared with non-CMO patients. On multivariate analysis, severe stroke measured by the NIHSS score (odds ratio [OR] = 1.2; 95% confidence interval [CI] = 1.1–1.4), infarction of the insular cortex (OR = 12.9; 95% CI = 1.4–118.4), and presence of cerebral edema with herniation (OR = 9.4; 95% CI = 2.5–35.5) were associated with transition to CMO. Conclusions: The presence of severe stroke, infarction of the insular cortex, and cerebral edema with herniation were associated with utilization of CMO in AIS. Impairment of multiple neurological functions served by the insular cortex could play a role in transition to CMO. [ABSTRACT FROM AUTHOR]

Introduction: Steroids are commonly used for managing brain edema in patients with glioblastoma multiforme (GBM), treated with surgery and concomitant temozolomide-based chemoradiotherapy (CTRT). The adverse effects of glucocorticoids include lymphopenia, hyperglycemia, and risk of infection. We report the results of a meta-analysis evaluating the effects of steroids on outcome when associated with the treatment of GBM. Methods: PubMed, the Cochrane Library, and Embase were searched from inception until September 2019 for observational or prospective studies reporting prognosis of adult patients with GBM and treated or not treated with steroids. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The effect size was reported as hazard ratios (HRs) with a 95% confidence interval (CI), and an HR > 1 associated with the worst outcome in steroid users compared to non-users. Results: Twenty-two publications were retrieved from studies selected for a total of 8,752 patients. In the primary analysis (n = 22 studies reporting data), OS was reduced in GBM patients taking steroids during treatment (HR = 1.54, 95% CI 1.37–1.75; p < 0.01). Similarly, PFS was inferior in steroid users in n = 9 studies with data available (HR = 1.28, 95% CI 1.1–1.49; p < 0.01). Conclusions: In patients with GBM and treated with RT and/or CT, association with steroids significantly reduces survival and PFS. Use of the lowest dose of glucocorticoids for the shortest period needed to achieve the treatment goals and prevention of steroid-associated complications are essential aims of treatment of this disease. [ABSTRACT FROM AUTHOR]

Tenuigenin (TNG) is an extract obtained from Polygalae Radix. It possesses anti-inflammatory, antioxidant, and neuroprotective properties. However, the potential mechanism of TNG in intracerebral hemorrhage (ICH) has not been well studied. In the present study, we aimed to identify the prospective mechanism of TNG in treating ICH. A total of 120 mice were divided into five groups: Sham group, ICH + vehicle group, ICH + TNG(8 mg/kg), ICH + TNG(16 mg/kg), and ICH + TNG(32 mg/kg). The modified Garcia test and beam walking test were carried out at 24 h and 72 h after ICH. Brain water content, haematoma volume and hemoglobin content examinations were performed at 72 h after ICH. TMT-based quantitative proteomics combined with bioinformatics analysis methods was used to distinguish differentially expressed proteins (DEPs) to explore potential pharmacological mechanisms. Western blotting was performed to validate representative proteins. Our results showed that the optimal dose of TNG was 16 mg/kg, which could markedly improve neurological functions, and reduce cerebral oedema, haematoma volume and hemoglobin levels 72 h after ICH. A total of 404 DEPs (353 up-and 51 downregulated) were identified in the ICH + vehicle vs. sham group, while 342 DEPs (306 up-and 36 downregulated) and 76 DEPs (28 up-and 48 downregulated) were quantified in the TNG vs. sham group and TNG vs. ICH + vehicle group, respectively. In addition, a total of 26 DEPs were selected according to strict criteria. Complement and coagulation cascades were the most significantly enriched pathways, and two proteins (MBL-C and Car1) were further validated as hub molecules. Our results suggested that the therapeutic effects of TNG on ICH were closely associated with the complement system, and that MBL-C and Car1 might be potential targets of TNG for the treatment of ICH. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: Non-traumatic cardiac arrest (CA) and return of spontaneous circulation (ROSC) after cardiopulmonary resuscitation (CPR) are often associated with multiple pathologies. Expecting a high prevalence of important findings, a whole-body CT (WBCT) could be of relevance for therapy. The aim of this study is to investigate the feasibility and diagnostic yield of an early WBCT in this setting.Methods: This single-center retrospective study included 100 consecutive patients (27 female; 73 male; mean age 68.5± 12.57 years) with non-traumatic, in- and out-of-hospital CA and ROSC following CPR, who underwent a contrast-enhanced WBCT within 6 h after ROSC over 12 months. CT findings were determined corresponding to anatomical region.Results: Early WBCT was successfully carried out in 100% of the patients with CA and ROSC after CPR. Acute pathologies were found not only in the chest but also in the head (15%) and the abdomen (6%). Early global brain edema (n = 12), acute stroke (n = 3), pulmonary embolism (n = 10), pneumothorax (26%), acute abdominal pathologies (n = 6), iatrogenic bleeding (4%), and CPR-related injuries (93%) were detected by CT right from the beginning of the post-cardiac arrest care.Conclusions: An early WBCT is feasible and provides added diagnostic value for patients with ROSC after non-traumatic CA. [ABSTRACT FROM AUTHOR]

Cerebral edema, a common and often fatal companion to most forms of acute central nervous system disease, has been recognized since the time of ancient Egypt. Unfortunately, our therapeutic armamentarium remains limited, in part due to historic limitations in our understanding of cerebral edema pathophysiology. Recent advancements have led to a number of clinical trials for novel therapeutics that could fundamentally alter the treatment of cerebral edema. In this review, we discuss these agents, their targets, and the data supporting their use, with a focus on agents that have progressed to clinical trials. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood brain barrier (BBB) breakdown, cerebrospinal fluid and blood glutamate levels. Anxiety-like behavior and levels of blood alanine and α-ketoglutarate were measured in naïve rats treated with pyruvate, as a control. Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. Pyruvate treatment reduced lesion volume, brain edema and the extent of BBB permeability 24 h post-MCAO. Naïve rats treated with pyruvate showed increased levels of α-ketoglutarate. Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels. • Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. • Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. • Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. • There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. • Our main conclusion was that glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels. [ABSTRACT FROM AUTHOR]

• BpV(pic) plays a neuroprotective effect in rat traumatic brain injury.BpV(pic) inhibits TBI-induced M1 microglial polarization via AKT/p65 signaling pathway. • BpV(pic) alleviates the increase of microglia in TBI lesion region. Traumatic brain injury (TBI) is a major cause of motor and cognitive impairment in young adults. It is associated with high mortality rates and very few effective treatment options. Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is an commercially available inhibitor of Phosphatase and tensin homolog (PTEN). Previous studies have shown that bpV(pic) has protective effects in central nervous system. However, the role of bpV(pic) in TBI is unclear. In this study we aimed to investigate the neuroprotective role of bpV(pic) in rat TBI model. We found that injection of bpV(pic) significantly reduces brain edema and neurological dysfunction after TBI and this is mediated by AKT pathway. TBI is known to promote the M1 pro-inflammatory phenotype of microglial polarization and this effect is inhibited by bpV(pic) treatment which, instead promotes M2 microglial polarization in vivo and in vitro. We also found evidence of bpV(pic)-regulated neuroinflammation mediated by AKT activation and NF-κB p65 inhibition. BpV(pic) treatment also suppressed microglia in the peri-TBI region. MCP-1 is known to recruit monocytes and macrophages to promote inflammation, we show that bpV(pic) can inhibit TBI-induced up-regulation of MCP-1 via the AKT/NF-κB p65 signaling pathway. Taken together, our findings demonstrate that bpV(pic) plays a neuroprotective role in rat TBI, which may be achieved by inhibiting M1 microglia polarization and MCP-1 expression by modulating AKT/NF-κB p65 signaling pathway. [ABSTRACT FROM AUTHOR]

• Tolvaptan attenuated brain edema after intracerebral hemorrhage. • Tolvaptan alleviated neurological deficits after intracerebral hemorrhage. • Tolvaptan prevented blood brain barrier destruction after intracerebral hemorrhage. Arginine-vasopressin (AVP) is believed to be positively correlated with the brain edema formation, but the underlying mechanism is still unclear. In this study, we explored the role of the V2 receptors antagonist tolvaptan on brain edema following intracerebral hemorrhage (ICH) with a rat model. Animals were randomly given tolvaptan or vehicle through oral gavage at 12 h, 36 h, and 60 h after ICH surgery. Brain swelling (%), brain water content(BWC), neurological scores, Evans blue fluorescence and blood-brain barrier (BBB) tight junction proteins were measured to evaluate the effect of tolvaptan in ICH. We found that tolvaptan alleviated the brain swelling (%), decreased the BWC growth, and attenuated the neurological deficits after ICH (p < 0.05, vs vehicle). What's more, tolvaptan increased the expression of ZO-1 and occludin (p < 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9. These results provided evidence supporting the use of tolvaptan for ICH-induced brain edema. Large animal experiments are required to further explore the efficacy and mechanism of tolvaptan in ICH treatment. [ABSTRACT FROM AUTHOR]

Efficacy of minimally invasive craniopuncture with the YL-1 puncture needle (hard-channel) and soft drainage tube (soft-channel) in treating hypertensive intracerebral hemorrhage (HICH). A total of 150 patients with HICH were randomly assigned into 3 groups: conservative group (n = 50), hard-channel group (n = 50), and soft-channel group (n = 50). Computed tomography, National Institutes of Health Stroke Scale (NIHSS) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum and in drainage fluid were examined on days 2, 4, and 6 after operation. Compared with the conservative group, the serum levels of IL-6, TNF-α, and MDA were decreased and SOD was increased (P < 0.05); volumes of hematoma and perihematomal edema as well as NIHSS were reduced (P < 0.05) in minimally invasive groups on days 7, 14, and 28 after operation. Compared with the hard-channel group, the serum levels of IL-6, TNF-α, MDA, and SOD showed the same trend as above in the soft-channel group. In the soft-channel group, MDA was reduced and SOD was increased in brain drainage fluid on days 2, 4, and 6 (P < 0.05); volumes of hematoma and perihematomal edema on days 14 and 28 were found to be reduced compared with the hard-channel group (P < 0.05). There was no significant difference of volumes of hematoma and perihematomal edema on day 7 between minimally invasive groups. NIHSS of the soft-channel group appeared to be significantly reduced on days 7, 14, and 28 after operation (P < 0.05). Soft-channel minimally invasive craniopuncture is an ideal technique for treating HICH, with advantages of alleviating cerebral edema, reducing oxidative stress, and inhibiting inflammatory response. [ABSTRACT FROM AUTHOR]

Dexamethasone is a standard treatment for cerebral edema after brain tumor surgery. However, its side effects can negatively impact the quality and safety of care provided to patients. Sparse evidence exists in the literature regarding postoperative steroid dosing to guide clinicians. The objective of this study was to determine if a new reduced exogenous steroid taper (REST) protocol would effectively treat postoperative cerebral edema while reducing the incidence of steroid-related side effects including diabetes, hypertension, and insomnia. A REST protocol (dexamethasone 38.5 mg tapered over 10 days) was instituted for patients with postoperative brain tumor of a single surgeon. Historical controls treated with a high-dose taper (dexamethasone 117 mg taper over 17 days) were selected to match for baseline characteristics. Outcomes of new or worsened diabetes, hypertension, and insomnia, as well as length of stay (LOS) and 30-day readmission rates, were compared. Twenty-five patients were included in each group. There were no significant differences in baseline characteristics. The REST group received a median of 34.5 mg (interquartile range, 32–41 mg) of dexamethasone, whereas controls received 43 mg (interquartile range, 16–91 mg) (P = 0.04). There was a significant reduction in the incidence of new or worsened hypertension in the REST group (0%) compared with controls (20%, P = 0.02). No difference was seen in the rates of diabetes mellitus, insomnia, LOS, or 30-day readmission rates. A reduced steroid taper after brain tumor surgery significantly reduced the incidence of hypertension without increasing LOS or 30-day readmissions compared with controls treated with a high-dose taper. [ABSTRACT FROM AUTHOR]

Cerebral involvement especially brain abscess is life-threatening complication and major cause of death during Scedosporium apiospermum infection. However, little is known about pathogenesis of brain oedema associated with abscess in scedosporiosis. Experimental scedosporiosis was conducted in BALB/cMlac mice to characterize the presence of brain oedema, its type, and its related mechanisms focusing on aquaporin (AQP)-4, nuclear factor erythroid-2 related factor (Nrf-2), and tumor necrotic factor (TNF)-α. The results revealed that S. apiospermum infection induced severe inflammatory environment relevant to TNF-α expression and cytogenic oedema-associated brain abscess predominately in cerebrum of immunocompromised mice without voriconazole treatment reflecting to downregulation of AQP-4 in neighboring abscess areas and oedematous blood vessels. Downregulation of Nrf-2 in neuronal cells and myelin degeneration were significantly observed in nontreated mice. In summary, oxidative stress, severe inflammatory response, and space-occupying mass from abscess formation inducing tissue hypoxia might be the postulate causes of oedema induced by scedosporiosis. [ABSTRACT FROM AUTHOR]

Background: Stereotactic radiosurgery (SRS) is indicated for a spectrum of brain tumors and is often an outpatient procedure, though severe disease may precipitate inpatient treatment. Readmission following inpatient SRS for brain tumors is not well understood. Objectives: To characterize rate, associative factors, and predictors of SRS readmission. Methods: Retrospective analysis of inpatients treated with SRS for brain neoplasms was conducted (2010-2014 Nationwide Readmissions Database). Diagnoses upon readmission were characterized. Associations with 30-day readmission were identified using multivariate analyses. Results: Of 2,553 patients undergoing SRS, 390 were readmitted (15.3%) within 30 days. Leading readmission diagnoses were infectious or embolic. Neurological readmissions of intracerebral hemorrhage (2.1%) and cerebral edema (1.5%) were rare. Malignant tumors (OR=1.60, p=0.007) and discharge to facility (OR=1.41, p=0.004) were associated with readmission. Conclusion: Inpatients receiving SRS for brain tumors have a 15.3% 30-day readmission rate. Neurologic readmissions were rare, underscoring the neurological safety of SRS, even in sick inpatients. [ABSTRACT FROM AUTHOR]

Background: Because osmotic fluid shifts may occur over the blood-brain barrier, patients with acute brain injury are theoretically at risk of surges in intracranial pressure (ICP) during hemodialysis. However, this remains poorly investigated. We studied changes in ICP during hemodialysis in such patients.Methods: We performed a retrospective study of patients with acute brain injury admitted to Rigshospitalet (Copenhagen, Denmark) from 2012 to 2016 who received intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) while undergoing ICP monitoring. Data from each patient's first dialysis session were collected. Area under the curve divided by time (AUC/t) for ICP was calculated separately before and during dialysis.Results: Thirteen patients were included. During dialysis, ICP increased from a baseline of 11.9 mm Hg (median; interquartile range 6.3-14.7) to a maximum of 21 mm Hg (18-27) (P = 0.0024), and AUC/t for ICP was greater during dialysis (15.2 (13.4-18.8) vs 11.7 mm Hg (6.4-15.1), P = 0.042). The maximum ICP increase was independent of dialysis modality, but peak values were reached earlier in patients treated with IHD (N = 4) compared to CRRT (N = 9) (75 [30-90] vs 375 min [180-420] after start of treatment, P = 0.0095). The maximum ICP increase correlated positively to the baseline plasma urea concentration (Spearman's r = 0.69, P = 0.017).Conclusion: Hemodialysis is associated with increased ICP in neurocritically ill patients, and the magnitude of the increase may be related to initial plasma urea levels. [ABSTRACT FROM AUTHOR]

Intraoperative indocyanine green (ICG) videoangiography is widely used in patients undergoing neurosurgery. FLOW800 is a recently developed analytical tool for ICG videoangiography to assess semi-quantitative flow dynamics; however, its efficacy is unknown. In this study, we evaluated its functionality in the assessment of flow dynamics of arteriovenous malformation (AVM) through ICG videoangiography under clinical settings. ICG videoangiography was performed in the exposed AVM in eight patients undergoing surgery. FLOW800 analysis was applied directly, and gray-scale and color-coded maps of the surgical field were obtained. After surgery, a region of interest was placed on the individual vessels to obtain time-intensity curves. Parameters of flow dynamics, including the maximum intensity, transit time, and cerebral blood flow index, were calculated using the curves. The color-coded maps provided high-resolution images; however, reconstruction of colored images was restricted by the depth, approach angle, and brain swelling. Semi-quantitative parameters were similar among the feeders, niduses, and drainers. However, a higher cerebral blood flow index was observed in the feeders of large AVM (>3 cm) than in those of small AVM (P < 0.05). Similarly, the cerebral blood flow index values were positively correlated with the nidus volume (P < 0.01). FLOW800 enabled visualization of the AVM structure and safer resection, except in case of deep-seated AVM. Moreover, semi-quantitative values in the individual vessels through using ICG intensity diagram showed different patterns according to size of the AVM. ICG videoangiography showed good performance in evaluating flow dynamics of the AVM in patients undergoing surgery. [ABSTRACT FROM AUTHOR]

Abstract Background Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour–related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. Patients and methods Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. Results Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. Conclusions Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov. Highlights • A reduced steroid requirement in patients taking angiotensin receptor blockers (ARBs) was reported in a retrospective series. • This randomised trial was designed to assess if the addition of ARBs (Losartan) to standard of care can reduce steroid requirement in patients with de novo GBM. • ARBs did not show any impact on steroid requirements during radiotherapy in this trial. A trend towards reduction of peritumoural oedema on magnetic resonance imaging over time was seen but did not reach statistical significance. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the effects of conivaptan, an arginine vasopressin antagonist, and mannitol, a sugar alcohol, on cerebral ischemia-induced brain injury and edema in rats. Materials and Methods: Fifty-eight 8-week-old male Sprague Dawley rats were randomly divided into five groups: control, ischemia-reperfusion (I/R)+saline, I/R+mannitol, I/R+10 mg/ml conivaptan, and I/R+20 mg/ ml conivaptan. Cerebral ischemia was induced by common carotid artery occlusion for 30 minutes. Saline, mannitol, or conivaptan were administered intravenously at the onset of reperfusion. Blood and brain tissue samples were taken at the 6th hour of reperfusion. The electrolytes (Na+-K+-Cl-), osmolality arginine vasopressin, albumin, progranulin (PGRN), neuron-specific enolase (NSE), and myeloperoxidase activity were measured in rat serum samples. Brain frontal/hippocampal sections were stained with hematoxylin-eosin and TUNEL techniques to evaluate histopathological changes. Results: Statistical analyses revealed that conivaptan caused significant changes in the electrolyte, NSE, and PGRN levels and osmolality when compared with mannitol. Conivaptan treatment showed positive effects on serum biochemistry and tissue histology Conclusion: Our findings revealed that conivaptan shows more diuretic activity than mannitol and triggers neither any damages nor edema in the brain tissue. This study may provide beneficial information for the development of treatment strategies for ischemia-related cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Resuscitation strategies for combined traumatic brain injury (TBI) with haemorrhage in austere environments are not fully established. Our aim was to establish the effects of various saline concentrations in a murine model of combined TBI and haemorrhage, and identify an effective resuscitative strategy for the far-forward environment. Methods: Male C57BL/6 mice underwent closed head injury and subjected to controlled haemorrhage to a systolic blood pressure of 25 mmHg via femoral artery cannulation for 60 min. Mice were resuscitated with a fixed volume bolus or variable volumes of fluid to achieve a systolic blood pressure goal of 80 mmHg with 0.9% saline, 3% saline, 0.1-mL bolus of 23.4% saline, or a 0.1-mL bolus of 23.4% saline followed by 0.9% saline (23.4+). Results: 23.4% saline and 23.4+ resulted in higher mortality at 6 h compared to 0.9% saline. Use of 3% saline required less volume to achieve targeted resuscitation, did not affect survival, and did not exacerbate post-traumatic inflammation. While 23.4+ resuscitation utilized lower volume, it resulted in hypernatremia, azotemia, and elevated systemic pro-inflammatory cytokines. All groups except 3% saline demonstrated progression of neuron damage, with cerebral oedema highest with 0.9% saline. Conclusions: 3% saline demonstrated favourable balance of survival, blood pressure restoration, minimization of inflammation, and prevention of ongoing neurologic injury without contributing to significant physiologic derangements. 23.4% saline administration may not be appropriate in the setting of concomitant hypotension. [ABSTRACT FROM AUTHOR]

Background: Mannitol 20% is used to treat patients with decreased consciousness and as the first line of treatment to reduce intracranial pressure (ICP). However, its application in pediatric patients is still based on minimal evidence. This study was performed to determine the predictive factors of clinical outcomes in pediatric patients with brain edema in the pediatric intensive care unit (PICU). Methods: This prospective cohort study was conducted in the PICU, Sanglah Hospital Denpasar, Bali, Indonesia. The subjects were chosen by consecutive sampling from July 2016 to July 2017. The primary outcome variable was the patient's clinical outcome. A chi-square test was used to evaluate the association between the timing of mannitol administration and the patient's clinical outcome. Multivariate analysis was performed on all variables with p≤0.25. Results: Forty-one patients were included in the study, 65% of them were male, 65% had good nutritional status, 90% had non-traumatic brain injury, and 73% had confirmed intracranial infection. The risk of sequelae or death for patients in a coma was 1.8 times greater than that of non-comatose patients (p=0.018; CI 95% 1.119-3.047). Based on the timing of mannitol administration from the onset of decreased consciousness, the risk of sequelae or death in patients who received mannitol after 24 hours was 2.1 times higher than that in patients who received mannitol within 24 hours (p=0.006; CI 95% 1.167-3.779). Based on multivariate analysis, only two variables were associated with the patient's clinical outcome: pediatric Glasgow coma scale (PGCS) ≤3 (p=0.03) and timing of mannitol administration >24 hours (p=0.01). Conclusion: Early administration (<24 hours) of mannitol and high PGCS are related to favorable outcomes in patients with brain edema in the PICU. [ABSTRACT FROM AUTHOR]

High-mountain sickness is characterized by brain and pulmonary edema and cognitive deficits. The definition can be fulfilled by a rat model of high-altitude exposure (HAE) used in the present study. This study aimed to investigate the protective effect of hyperbaric oxygen therapy (HBO2T) and to determine the underlying mechanisms. Rats were subjected to an HAE (9.7% O2 at 0.47 absolute atmosphere of 6,000 m for 3 days). Immediately after termination of HAE, rats were treated with HBO2T (100% O2 at 2.0 absolute atmosphere for 1 hour per day for 5 consecutive days) or non-HBO2T (21% O2 at 1.0 absolute atmosphere for 1 hour per day for 5 consecutive days). As compared to non-HAE+non-HBO2T controls, the HAE+non-HBO2T rats exhibited brain edema and resulted in cognitive deficits, reduced food and water consumption, body weight loss, increased cerebral inflammation and oxidative stress, and pulmonary edema. HBO2T increased expression of both hippocampus and lung heat shock protein (HSP-70) and also reversed the HAE-induced brain and pulmonary edema, cognitive deficits, reduced food and water consumption, body weight loss, and brain inflammation and oxidative stress. Decreasing the overexpression of HSP-70 in both hippocampus and lung tissues with HSP-70 antibodies significantly attenuated the beneficial effects exerted by HBO2T in HAE rats. Our data provide in vivo evidence that HBO2T works on a remodeling of brain/lung to exert a protective effect against simulated high-mountain sickness via enhancing HSP-70 expression in HAE rats. [ABSTRACT FROM AUTHOR]

Objective: Remote limb ischemic post-conditioning (RLIPostC) has been shown to be neuroprotective in cerebral ischemia, whereas the effect of RLIPostC on synaptogenesis remains elusive. In the present study, we investigated the effects of RLIPostC on synaptogenesis in an experimental stroke rat model. Methods: Sprague-Dawley rats were subjected to left middle cerebral artery occlusion (MCAO) and were randomly divided into a control group, an RLIPostC group and a sham group. The RLIPostC group received three cycles of RLIPostC treatment immediately after reperfusion (ten minutes ischemia and ten minutes reperfusion in bilateral femoral artery). The neurological function was assessed by neurological deficit scores and the foot fault test at days 7 and 14 after MCAO. At day 14 after MCAO, the infarct volume and oedema were determined by cresyl violet (CV) staining and by measuring brain water content, respectively. Synaptogenesis was evaluated by western blotting and immunofluorescence staining. Results: Our results showed that RLIPostC treatment significantly promoted the recovery of behavioural function, reduced infarct volume and brain oedema, and increased the expressions of SYN1, PSD95 and GAP43. Conclusions: These results confirmed that RLIPostC treatment for cerebral ischemia was safe and effective. A possible molecular mechanism of the beneficial effects of RLIPostC treatment may be the promotion of synaptogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article focuses on the International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines for diabetic ketoacidosis and the hyperglycemic hyperosmolar state. It mentions biochemical criteria for the diagnosis of diabetic ketoacidosis (DKA) include hyperglycemia, serum bicarbonate and ketonemia. It further mentions risk factors for DKA and treatment options such as insulin therapy, and potassium administration.

Chronic intermittent hypoxia (CIH) is one of the main features of obstructive sleep apnea (OSA), which is also commonly associated with neurocognitive impairments. The present study aimed to elucidate the beneficial effect of curcumin on CIH-induced brain injuries. Male balb/c mice (6 ∼ 8 weeks) were exposed to normoxia or a pattern of CIH (8 h/day, cycles of 180 s each, hypoxia: 5% O 2 for 50 s, reoxygenation: 21% O 2 for 50 s) for 10 weeks, along with daily curcumin treatment (50, 100, or 200 mg/kg, intragastrically) or its vehicle. The results showed that CIH induced significant brain edema, as well as neuronal apoptosis and astrogliosis in the cerebral cortex, brainstem, and cerebellum regions of brain. In addition, increased astrocytic AQP4 expression and activation of p38 MAPK pathway were observed after CIH exposure. Curcumin dose-dependently mitigated the brain edema and relevant cell alterations, showing a neuroprotective effect in CIH-induced brain injury. Together, these results suggest curcumin ameliorates the CIH-induced brain injuries, including brain edema, neuronal death and astrogliosis. The beneficial role of curcumin is mediated partially by regulating AQP4 and p38 MAPK pathway. [ABSTRACT FROM AUTHOR]

Objectives: Chimeric antigen receptor T-cell therapy, a type of immune effector therapy for cancer, has demonstrated encouraging results in clinical trials for the treatment of patients with refractory hematologic malignancies. Nevertheless, there are toxicities specific to these treatments that, if not recognized and treated appropriately, can lead to multiple organ failure and death. This article is a comprehensive review of the available literature and provides, from a critical care perspective, recommendations by experienced intensivists in the care of critically ill adult chimeric antigen receptor T-cell patients.Data Sources: PubMed and Medline search of articles published from 2006 to date.Study Selection: Clinical studies, reviews, or guidelines were selected and reviewed by the authors.Data Extraction: Not available.Data Synthesis: Not available.Conclusions: Until modifications in chimeric antigen receptor T-cell therapy decrease their toxicities, the intensivist will play a leading role in the management of critically ill chimeric antigen receptor T-cell patients. As this novel immunotherapeutic approach becomes widely available, all critical care clinicians need to be familiar with the recognition and management of complications associated with this treatment. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral artery gas embolism (CAGE) is a rare but serious adverse event with potentially devastating neurologic sequelae. Bronchoscopy is a frequently performed procedure but with only a few reported cases of CAGE. Methods: We report the first documented case of CAGE associated with electromagnetic navigational bronchoscopy. Results: A 61-year-old man with a left lower lobe nodule underwent electromagnetic navigational bronchoscopy. The target lesion underwent transbronchial biopsy, brushing and an end-procedure lavage. Following the procedure, he developed seizures, evidence of hypoxic injury and cerebral edema, and air emboli were seen on computed tomography imaging. He then underwent treatment with hyperbaric oxygen with a full and complete neurologic recovery. Review of other cases reported in the literature suggests improved neurologic outcomes with hyperbaric oxygen treatment. Conclusions: Biopsy techniques performed during bronchoscopy and electromagnetic navigational bronchoscopy can result in CAGE. Comparison with other reported cases suggests improved neurologic outcomes in those treated with hyperbaric oxygen. Prompt recognition of this complication and timely treatment with hyperbaric oxygen are the cornerstones to recovery. [ABSTRACT FROM AUTHOR]

Objective: This study examines temporal trends in treatment‐related outcomes surrounding a diabetic ketoacidosis (DKA) performance improvement intervention consisting of mandated intensive care unit admission and implementation of a standardized management pathway, and identifies physical and biochemical characteristics associated with outcomes in this population. Methods: A retrospective cohort of 1225 children with DKA were identified in the electronic health record by international classification of diseases codes and a minimum pH less than 7.3 during hospitalization at a quaternary children's hospital between April, 2009 and May, 2016. Multivariable regression examined predictors and trends of hypoglycemia, central venous line placement, severe hyperchloremia, head computed tomography (CT) utilization, treated cerebral edema and hospital length of stay (LOS). Results: The incidence of severe hyperchloremia and head CT utilization decreased during the study period. Among patients with severe DKA (presenting pH < 7.1), the intervention was associated with decreasing LOS and less variability in LOS. Lower pH at presentation was independently associated with increased risk for all outcomes except hypoglycemia, which was associated with higher pH. Patients treated for cerebral edema had a lower presenting mean systolic blood pressure z score (0.58 [95% confidence interval (CI) −0.02‐1.17] vs 1.23 [1.13‐1.33]) and a higher maximum mean systolic blood pressure (SBP) z score during hospitalization (3.75 [3.19‐4.31] vs 2.48 [2.38‐2.58]) compared to patients not receiving cerebral edema treatment. Blood pressure and cerebral edema remained significantly associated after covariate adjustment. Conclusion: Treatment‐related outcomes improved over the entire study period and following a performance improvement intervention. The association of SBP with cerebral edema warrants further study. [ABSTRACT FROM AUTHOR]

Glibenclamide (GBC) is an antidiabetic drug that is in a class of medications known as sulfonylureas, which play critical roles in attenuating brain edema and reducing mortality in ischemic stroke patients. Therapeutic hypothermia (TH) is another robust neuroprotectant that prevents brain swelling and improves the neurological outcomes of stroke patients. However, whether the combination of GBC and TH can be used as a reliable neuroprotectant in ischemic stroke remains largely unknown. We used the middle cerebral artery occlusion (MCAO) rat model as well as oxygen and glucose deprivation-reoxygenation (OGD/R) endothelial cells as ischemic stroke models to investigate the efficacy and mechanisms of treating ischemic stroke with the combination of GBC and TH. The serum glucose, mortality rate, neurobehavioral functions, tight junctions, endothelial cells and inflammatory cytokines were evaluated in the stroke models after treatment with GBC, TH or the combination of them. After 5-hour occlusion and subsequent reperfusion, rats exhibited a large volume of hemispheric swelling and a high mortality rate. Stroke rats treated with the combined therapy did not exhibit hypoglycemia. The combination of GBC and TH exhibited synergistic neuroprotective effects in stroke rats that were associated with greater reductions in edema volume, better improvement in neurobehavioral functions, prevention of tight junction loss, and reduction of expression of the inflammatory cytokines COX-2 and iNOS. In OGD/R endothelia cells, the combination reduced endothelial cell death. This study demonstrated that both GBC and TH are neuroprotective after the severe stroke; however, combined therapy with GBC and TH enhanced the efficiency and efficacy of the effects of TH and GBC in the treatment of ischemia. This combined therapy may facilitate the clinical translation of TH management for severe stroke. The combination of GBC and TH seems to be a feasible and promising clinical strategy to alleviate cerebral injury following severe stroke. [ABSTRACT FROM AUTHOR]

Since the 1980s, methylenedioxymethamphetamine (MDMA) has been a popular recreational drug, used particularly among those who attend raves and nightclubs. Over the past 3 years, the popularity of this drug has once again increased and there has been an associated rise in deaths. The pathophysiology of MDMA toxicity is complex and much remains to be understood. This article aims to increase readers' knowledge of patient presentations, the pathophysiology behind life-threatening toxicity, current treatments and the use of extracorporeal membrane oxygenation as a potential future treatment. [ABSTRACT FROM AUTHOR]

Central pontine myelinolysis (CPM) is rarely reported in pediatric patients with diabetic ketoacidosis (DKA). We report this case of a 16-year-old female with new onset diabetes presenting with DKA, who received aggressive fluid resuscitation and sodium bicarbonate in the emergency department. Later she developed altered mental status concerning for cerebral edema and received hyperosmolar therapy with only transient improvement. Soon she became apneic requiring emergent endotracheal intubation. MRI brain showed cerebral edema, CPM, and subdural hemorrhage. She was extubated on day seven and exhibited mild dysmetria, ataxia, unilateral weakness, and neglect. Upon discharge she was able to ambulate with a walker and speak and eat without difficulty. Although less common than cerebral edema, CPM should be considered in DKA patients with acute neurologic deterioration. Fluid and bicarbonate therapy should be individualized, but larger studies would help guide the management. Although poor outcomes are reported in CPM, favorable outcomes are possible. [ABSTRACT FROM AUTHOR]

Purpose: Potential dosimetric and clinicopathologic predictors of radiation-induced brain edema after single-fraction or multifraction stereotactic radiosurgery (SRS) for non-base of skull (non-BOS) meningiomas are summarized based on a systematic review of the published literature.Methods and Materials: Reviewed studies (PubMed indexed from 1998 through 2017) included all or some non-BOS meningioma patients, reported risks of edema after SRS, and correlated dosimetric and/or nondosimetric measures with the magnitude of risk.Results: Twenty-six studies reporting risks of edema after SRS for meningioma are reviewed. The treatment techniques as well as distribution of tumor locations, target dosing, and target volume varied across studies. Among 13 studies that included only non-BOS tumors or separately grouped non-BOS tumors, symptomatic edema occurred in 5% to 43% of patients and any edema occurred in 28% to 50%. The reported average time to onset of edema ranged from approximately 3 to 9 months in most studies. Factors reported to significantly correlate with increased risks of edema and/or symptomatic edema after SRS for meningioma include the following: greater tumor margin and/or maximum dose, greater tumor size and/or volume, non-BOS (particularly parasagittal) location, no prior resection for meningioma, and presence of pretreatment edema. Nevertheless, the extent and significance of these factors were inconsistent across studies. Potentially important dosimetric factors, such as volume of brain or tissue receiving single-fraction doses > 10 to 12 Gy, are not well studied.Conclusions: The variability in risks of edema and in factors impacting those risks is likely a result of differences across studies in the clinicopathologic characteristics of the patient populations, as well as differences in treatment modalities and SRS planning and delivery parameters. More studies on pooled populations, grouped by potential prognostic factors such as tumor location and prior therapy, are needed to better understand dosimetric and nondosimetric factors predictive of edema risk after SRS for meningioma. [ABSTRACT FROM AUTHOR]

Background Hypertonic saline (HS) has been used clinically for treatment of cerebral edema for decades. Previously we have demonstrated that HS alleviates cerebral edema via regulating water/ion channel protein and attenuating neuroinflammation. However, whether HS treatment triggers microglia polarization and its regulatory mechanism during this process is unclear. Methods and results The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery occlusion (MCAO) were used for assessment of neuroinflammation and microglia functions. Treatment of 10% HS not only significantly reduced infarct size and ipsilateral ischemic hemispheric brain water content (BWC) via attenuating ischemia-induction of TNF-α, IL-1β, microglia M1 markers (iNOS, CD86) and miR-200b, but also increased neurotrophic factors such as IL-10 and IL-4, microglia M2 markers (Arg1, CD206) and Krüppel-like factor 4 (KLF4). Similar changes were confirmed in primary microglial cells subjected to hypoxia with/without HS in vitro . Importantly, overexpression of miR-200b was able to induce microglia M1 polarization via directly targeting KLF4. Restoring KLF4 expression abolished this effect. On the contrary, miR-200b inhibitor or KLF4 overexpression led to microglia M2 polarization. Mechanistically, KLF4 directly binds to promoter region of Agr1, thus inducing its transcription. Similar to treatment of HS, experimental overexpression of KLF4 in vivo exerted significant beneficial effects on ischemia-induced cerebral edema. However, knockdown of KLF4 abrogated the benefits of HS. Conclusions Hypertonic saline regulates microglial M2 polarization via miR-200b/KLF4 during its treatment of cerebral edema. This study may provide new insights of HS-related therapy for cerebral edema. [ABSTRACT FROM AUTHOR]

Background: Anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is an autoimmune disorder that often affects women of childbearing age, and maternal-fetal transfer of anti-NMDAR antibodies during pregnancy has been documented in both symptomatic and asymptomatic women. The effects of these antibodies on the fetus, however, are incompletely understood.Patient Description: This term infant exhibited depressed respiratory effort, poor feeding, and abnormal movements after birth. Magnetic resonance imaging revealed diffuse cerebral edema with ischemic and hemorrhagic injury. Her mother had experienced anti-NMDAR encephalitis secondary to an ovarian teratoma 18 months earlier. The baby's serum NMDAR antibody titer was elevated at 1:320. Intravenous immunoglobulin did not result in clinical improvement, and care was withdrawn on day of life 20. Her mother had an elevated serum NMDAR antibodies (1:80), positive CSF antibody titers, and a new ovarian teratoma.Conclusion: Routine testing of NMDAR antibodies in pregnant women with a previous history of anti-NMDAR encephalitis may be warranted. Infants born to these mothers should be closely monitored throughout pregnancy and after birth. [ABSTRACT FROM AUTHOR]

Brain edema and the associated increase in intracranial pressure are major consequences of traumatic brain injury (TBI) that accounts for most early deaths after TBI. We recently showed that acute severe trauma to cultured astrocytes results in cell swelling. We further examined whether trauma induces cell swelling in neurons and microglia. We found that severe trauma also caused cell swelling in cultured neurons, whereas no swelling was observed in microglia. While severe trauma caused cell swelling in both astrocytes and neurons, mild trauma to astrocytes, neurons, and microglia failed to cell swelling. Since extracellular levels of glutamate are increased in brain post-TBI and microglia are known to release cytokine, and direct exposure of astrocytes to these molecules are known to stimulate cell swelling, we examined whether glutamate or cytokines have any additive effect on trauma-induced cell swelling. Exposure of cultured astrocytes to trauma caused cell swelling, and such swelling was potentiated by the exposure of traumatized astrocytes to glutamate and cytokines. Conditioned medium (CM) from traumatized astrocytes had no effect on neuronal swelling post-trauma, while CM from traumatized neurons and microglia potentiated the effect of trauma on astrocyte swelling. Further, trauma significantly increased the Na–K–Cl co-transporter (NKCC) activity in neurons, and that inhibition of NKCC activity diminished the trauma-induced neuronal swelling. Our results indicate that a differential sensitivity to trauma-induced cell swelling exists in neural cells and that neurons and microglia are likely to be involved in the potentiation of the astrocyte swelling post-trauma. [ABSTRACT FROM AUTHOR]

Background: Rhubarb is a traditional Chinese medicine for treating traumatic brain injury (TBI). Purpose: The purpose of this study is to elucidate the potential mechanism of rhubarb by suppressing extracellular signal-regulated kinase (ERK) to ameliorate brain edema. Materials and Methods: Sprague-Dawley rats were separated into four groups at random. One group received 3 g/kg rhubarb, and another group received 12 g/kg rhubarb, and the vehicle group and sham group were administered the same dose of saline solution. The blood--brain barrier disruption and edema were detected by Evans blue extravasation and water content, respectively. ERK, Matrix metalloproteinase 9 (MMP-9), and zonula occluden-1 (ZO-1) in the damaged tissue were measured by western blot analysis and quantitative real-time polymerase chain reaction. Results: Rhubarb attenuated the brain edema after TBI, especially at the dose of 12 g/kg. Rhubarb significantly suppressed ERK, down-regulated MMP-9, and up-regulated ZO-1. Rhubarb might be a prospective therapeutic regimen to decrease edema in TBI. Conclusions: Rhubarb alleviates the edema by restraining the ERK signaling pathway. Our results contribute to the validation of the traditional use of rhubarb in the treatment of TBI and its mechanism. [ABSTRACT FROM AUTHOR]

Aim To quantify the exchange of water between cerebral compartments, specifically blood, tissue, perivascular pathways, and cerebrospinal fluid-filled spaces, on the basis of experimental data and to propose a dynamic global model of water flux through the entire brain to elucidate functionally relevant fluid exchange phenomena. Methods The mechanistic computer model to predict brain water shifts is discretized by cerebral compartments into nodes. Water and species flux is calculated between these nodes across a network of arcs driven by Hagen-Poiseuille flow (blood), Darcy flow (interstitial fluid transport), and Starling's Law (transmembrane fluid exchange). Compartment compliance is accounted for using a pressurevolume relationship to enforce the Monro-Kellie doctrine. This nonlinear system of differential equations is solved implicitly using MATLAB software. Results The model predictions of intraventricular osmotic injection caused a pressure rise from 10 to 22 mmHg, followed by a taper to 14 mmHg over 100 minutes. The computational results are compared to experimental data with R2 = 0.929. Moreover, simulated osmotic therapy of systemic (blood) injection reduced intracranial pressure from 25 to 10 mmHg. The modeled volume and intracranial pressure changes following cerebral edema agree with experimental trends observed in animal models with R2 = 0.997. Conclusion The model successfully predicted time course and the efficacy of osmotic therapy for clearing cerebral edema. Furthermore, the mathematical model implicated the perivascular pathways as a possible conduit for water and solute exchange. This was a first step to quantify fluid exchange throughout the brain. [ABSTRACT FROM AUTHOR]

Advances in medical care of the acute liver failure patient have led to a significant reduction in mortality related to the condition. Nevertheless, cerebral edema and ensuing brain herniation remains one of the top causes of demise in acute liver failure. Controversy remains regarding the utility of invasive intracranial pressure monitoring as well as usage of novel treatment modalities including therapeutic hypothermia. This review provides a brief summary into the pathophysiology and risk factors for developing cerebral edema in the context of acute liver failure; this review particularly provides a practical focus on general management of the patient with established cerebral edema as well as specific intracranial pressure-lowering strategies. [ABSTRACT FROM AUTHOR]

Objective Currently, the optimal surgical approach for bilateral aneurysms remains controversial. Alternative interventional methods, such as unilateral or bilateral approaches, have been used during a single session or 2 different sessions. The unilateral approach can be used successfully to treat contralateral aneurysms that develop in a paramedian location. However, such an approach is more difficult for treating contralateral aneurysms in more distant locations. The unilateral approach can decrease complication rates, operation time, and length of hospital stay. In this study, we aimed to identify when the unilateral approach should be chosen in patients with bilateral middle cerebral artery (MCA) aneurysms and to compare the effect of each approach on the operation time and duration of hospital stay. Methods Between March 2003 and May 2016, 17 bilateral MCA aneurysms were diagnosed in patients who presented to our clinic with complaints of headache and a diagnosis of subarachnoid hemorrhage. The extent of the cerebral edema, A1 + M1 distance on the opposite site, and configuration of the contralateral aneurysm were determined by preoperative radiologic studies. Based on these findings, 7 patients underwent unilateral surgery, and 10 patients received the bilateral approach. Results The 2 groups had a very similar postoperative course. Nonetheless, the operation time and hospital stay were significantly longer for patients who underwent bilateral surgery than those treated with the unilateral approach. Conclusions In selected patients with bilateral MCA aneurysms, the unilateral approach is a favorable alternative that is less invasive, decreases the operation time and hospital stay, and leads to fewer complications. [ABSTRACT FROM AUTHOR]

Background and Purpose: Streptococcus pneumoniae is the most common cause of bacterial meningitis in adults and is characterized by high lethality and substantial cognitive disabilities in survivors. Here, we have studied the capacity of an established therapeutic agent, magnesium, to improve survival in pneumococcal meningitis by modulating the neurological effects of the major pneumococcal pathogenic factor, pneumolysin.Experimental Approach: We used mixed primary glial and acute brain slice cultures, pneumolysin injection in infant rats, a mouse meningitis model and complementary approaches such as Western blot, a black lipid bilayer conductance assay and live imaging of primary glial cells.Key Results: Treatment with therapeutic concentrations of magnesium chloride (500 mg·kg-1 in animals and 2 mM in cultures) prevented pneumolysin-induced brain swelling and tissue remodelling both in brain slices and in animal models. In contrast to other divalent ions, which diminish the membrane binding of pneumolysin in non-therapeutic concentrations, magnesium delayed toxin-driven pore formation without affecting its membrane binding or the conductance profile of its pores. Finally, magnesium prolonged the survival and improved clinical condition of mice with pneumococcal meningitis, in the absence of antibiotic treatment.Conclusions and Implications: Magnesium is a well-established and safe therapeutic agent that has demonstrated capacity for attenuating pneumolysin-triggered pathogenic effects on the brain. The improved animal survival and clinical condition in the meningitis model identifies magnesium as a promising candidate for adjunctive treatment of pneumococcal meningitis, together with antibiotic therapy. [ABSTRACT FROM AUTHOR]

Cerebral thrombosis is one of the most common causes of cerebral infarction, and anticoagulation therapy is a routine treatment in patients with hemorrhagic cerebral venous thrombosis. The hemostatic function of platelets is important for the anticoagulation therapy of thrombosis. Glycoprotein VI (GPVI) is reported as the major signaling receptor for collagen and is exclusively expressed on platelets and megakaryocytes, initiating platelet recruitment at sites of vascular injury and demonstrating numerous beneficial effects for patients with cerebral thrombosis. In the present study, thrombus formation and platelet adhesion following endothelial injury was monitored in the jugular vein by intra‑vital fluorescence microscopy. The morphological and clinical observations of cerebral thrombosis were investigated and analyzed in a mouse model with cerebral thrombosis. In addition, the present study investigated the effect of fusion protein GPVI modified with Fc and PEG, which is specifically linked to the extracellular domain of GPVI (GPVI‑Fc‑PEG), on thrombus formation following vessel wall injury and on experimental mice with cerebral thrombosis. The maximum tolerated dose (MTD) was identified as 0.18 mg. GPVI‑Fc‑PEG competitively bound to and prevented von Willebrand Factor‑collagen interactions. The results of the present study demonstrated that cerebral thrombosis was greatly relieved and improved functional outcomes treatment with an MTD of GPVI‑Fc‑PEG following endothelial injury, compared with GPVI‑Fc‑treated mice. In addition, cerebral edema and infarct size was improved compared with GPVI‑Fc‑treated mice with ischemic stroke immediately prior to reperfusion. Furthermore, treatment of GPVI‑Fc‑PEG led to increased reperfusion and improved survival following cerebral thrombosis compared with treatment with either single agent alone. Taken together, GPVI‑Fc‑PEG relieved cerebral thrombosis following ischemic stroke and improved prognostic preclinical outcomes without intracranial bleeding, which suggested that GPVI‑Fc‑PEG may be a potential candidate for cerebral thrombosis therapy. [ABSTRACT FROM AUTHOR]

Introduction Postoperative cerebral edema is a devastating complication in neurosurgical patients. Loss of blood-brain barrier integrity has been shown to lead to the development of brain edema following neurosurgical procedures. The aim of this study was to evaluate preconditioning with Crotalus helleri venom (Cv-PC) as a potential preventive therapy for reducing postoperative brain edema in the rodent SBI model. C. helleri venom is known to contain phospholipase A2 (PLA2), an enzyme upstream to cyclooxygenase-2 (COX-2) in the inflammatory cascade, acts to increase the production of inflammatory mediators, such as prostaglandins. We hypothesize that Cv-PC will downregulate the response of the COX-2 pathway to injury, thereby reducing the inflammatory response and the development of brain edema after SBI. Materials and methods 75 male Sprague Dawley rats (280–330 g) were divided to the following groups—naïve + vehicle, naïve + Cv-PC, sham, vehicle, Cv-PC, Cv-PC + NS398 (COX-2 inhibitor). Vehicle preconditioned and Cv-PC animals received either three daily subcutaneous doses of saline or C. helleri venom at 72 h, 48 h, and 24 h prior to surgery. In Cv-PC + NS398 animals, NS398 was administered intraperitoneally 1 h prior to each Cv-PC injection. Sham-operated animals received craniotomy only, whereas SBI animals received a partial right frontal lobectomy. Neurological testing and brain water content were assessed at 24 h and 72 h after SBI; COX-2 and PGE 2 expression was assessed at 24 h postoperatively by Western blot and immunohistochemistry, respectively. Results At 24 h after SBI, the vehicle-treated animals were observed to have increased brain water content (83.1 ± 0.2%) compared to that of sham animals (80.2 ± 0.1%). The brain water content of vehicle-treated animals at 72 h post-SBI was elevated at 83.3 ± 0.2%. Cv-PC-treated animals with doses of 10% LD 50 had significantly reduced brain water content of 81.92 ± 0.7% and 81.82 ± 0.3% at 24 h and 72 h, respectively, after SBI compared to that of vehicle-treated animals, while Cv-PC with 5% LD 50 doses showed brain water content that trended lower but did not reach statistical significance. At 24 h and 72 h post-SBI, Cv-PC-treated animals had significantly higher neurological score than vehicle-treated animals. The COX-2 over-expression characterized in SBI was attenuated in Cv-PC-treated animals; NS398 reversed the protective effect of Cv-PC on COX-2 expression. Cv-PC tempered the over-expression of the inflammatory marker PGE 2 . Conclusion Our findings indicate that Cv-PC may provide a promising therapy for reducing postoperative edema and improving neurological function after neurosurgical procedures. [ABSTRACT FROM AUTHOR]

Objectives: Hyponatremic encephalopathy, symptomatic cerebral edema due to a low osmolar state, is a medical emergency and often encountered in the ICU setting. This article provides a critical appraisal and review of the literature on identification of high-risk patients and the treatment of this life-threatening disorder.Data Sources, Study Selection, and Data Extraction: Online search of the PubMed database and manual review of articles involving risk factors for hyponatremic encephalopathy and treatment of hyponatremic encephalopathy in critical illness.Data Synthesis: Hyponatremic encephalopathy is a frequently encountered problem in the ICU. Prompt recognition of hyponatremic encephalopathy and early treatment with hypertonic saline are critical for successful outcomes. Manifestations are varied, depending on the extent of CNS's adaptation to the hypoosmolar state. The absolute change in serum sodium alone is a poor predictor of clinical symptoms. However, certain patient specific risks factors are predictive of a poor outcome and are important to identify. Gender (premenopausal and postmenopausal females), age (prepubertal children), and the presence of hypoxia are the three main clinical risk factors and are more predictive of poor outcomes than the rate of development of hyponatremia or the absolute decrease in the serum sodium.Conclusions: In patients with hyponatremic encephalopathy exhibiting neurologic manifestations, a bolus of 100 mL of 3% saline, given over 10 minutes, should be promptly administered. The goal of this initial bolus is to quickly treat cerebral edema. If signs persist, the bolus should be repeated in order to achieve clinical remission. However, the total change in serum sodium should not exceed 5 mEq/L in the initial 1-2 hours and 15-20 mEq/L in the first 48 hours of treatment. It has recently been demonstrated in a prospective fashion that 500 mL of 3% saline at an infusion rate of 100 mL per hour can be given safely. It is critical to recognize the early signs of cerebral edema (nausea, vomiting, and headache) and intervene with IV 3% sodium chloride as this is the time to intervene rather than waiting until more severe symptoms develop. Cerebral demyelination is a rare complication of overly rapid correction of hyponatremia. The principal risk factors for cerebral demyelination are correction of the serum sodium more than 25 mEq/L in the first 48 hours of therapy, correction past the point of 140 mEq/L, chronic liver disease, and hypoxic/anoxic episode. [ABSTRACT FROM AUTHOR]

Background: Space-occupying middle cerebral artery brain infarcts are associated with the development of brain edema, which may lead to cerebral herniation and death despite early hemicraniectomy. Aims: To evaluate the benefit of therapeutic hypothermia in patients with space-occupying cerebral infarction treated with hemicraniectomy within 48 h of stroke onset. Methods: Patients aged 18-60 years with space-occupying cerebral infarction treated with hemicraniectomy within 48 h and hypothermia (33-34°C) were selected from a single university hospital between 2001 and 2010 (n=53). Patients treated with hemicraniectomy alone served as comparison group (n=58), originating from three randomized controlled trials evaluating the effects of early decompressive surgery (DECIMAL, DESTINY, HAMLET). Primary outcome was the score on the modified Rankin scale at 12 months dichotomized between modified Rankin scale 0-3 and modified Rankin scale 4-6. Secondary outcome measures were modified Rankin scale score 0-4 and survival. Risk ratios were adjusted with Poisson regression. Results: Mean patient age was 48 years. Median time from stroke onset to hemicraniectomy was 23.5 h in both treatment groups. Treatment with hypothermia had no effect on the primary outcome (modified Rankin scale 0-3 versus 4-6 (13/53 (25%) versus 24/58 (41%)); adjusted risk ratio 0.66, 95% confidence interval 0.38-1.13). Fewer patients treated with hypothermia had a modified Rankin scale score of 0-4 (21/53 (40%) versus 42/58 (72%); adjusted risk ratio 0.53, 95% confidence interval 0.37-0.76) and fewer patients survived (26/53 (49%) versus 46/58 (79%); adjusted risk ratio 0.60, 95% confidence interval 0.44-0.82). Conclusions: In patients with space-occupying cerebral infarction, treatment with hypothermia had no additional benefit on functional outcome compared with treatment with hemicraniectomy alone. [ABSTRACT FROM AUTHOR]