Severe Brain Edema Research Articles

Intraoperative goal-directed fluid management and postoperative brain edema in patients having high-grade gliomas resections: a randomized trial.

Patients with high-grade gliomas often have severe brain edema. Goal-directed fluid management protects neurological function, but whether reduces postoperative brain edema remains unknown. Patients having elective resection of supratentorial malignant gliomas were randomly assigned to goal-directed versus routine fluid management. Patients assigned to goal-directed management group were given 3mL kg-1 hydroxyethyl starch solution when stroke volume variation exceeded 15% for 5 minutes. Fluid was managed per routine by attending anesthesiologists in reference patients. The primary outcome was cerebral edema volume after surgery as assessed by computerized tomography. A total of 480 eligible patients were randomly assigned to the goal-directed (n = 240) or the routine fluid management group (n = 240). The amounts of crystalloid (5.4 vs. 7.0ml kg-1 hour-1, P < 0.001), colloid (1.1 vs. 1.7ml kg-1 hour-1, P < 0.001), and overall fluid balance (0.3 vs. 1.9ml kg-1 hour-1, P < 0.001) were significantly lower in goal-directed fluid management. There was no significant difference in postoperative brain edema volume between groups (36.0cm3 vs. 38.9cm3, mean difference: 0.18cm3, 95% CI: -5.7 to 5.9). Goal-directed patients had lower intraoperative dural tension (risk ratio: 0.63, 95% CI: 0.50 to 0.80, P < 0.001). There was no significant difference in Karnofsky Performance Status between the two groups at 30 days after surgery. Goal-directed fluid therapy substantially reduced intravenous fluid volumes, but did not reduce postoperative brain edema in patients having brain tumor resections.

Cystatin C Attenuates Perihematomal Secondary Brain Injury by Inhibiting the Cathepsin B/NLRP3 Signaling Pathway in a Rat Model of Intracerebral Hemorrhage.

Secondary brain injury (SBI) is a noticeable contributor to the high mortality and morbidity rates associated with intracerebral hemorrhage (ICH), and effective treatment options remain limited. Cystatin C (CysC) emerges as a novel candidate for SBI intervention. The therapeutic effects and underlying mechanisms of CysC in mitigating SBI following ICH were explored in the current research. An in vivo ICH rat model was established by injecting autologous blood into the right caudate nucleus. Western blotting (WB) was utilized to assess the levels of CysC, cathepsin B (CTSB), and the NLRP3 inflammasome. Subsequently, the ICH rat model was treated with exogenous CysC supplementation or CysC knockdown plasmids. Various parameters, including Evans blue (EB) extravasation, brain water content, and neurological function in rats, were examined. RT-qPCR and WB were employed to determine the expression levels of CTSB and the NLRP3 inflammasome. The co-expression of CTSB, CysC, and NLRP3 inflammasome with GFAP, NeuN, and Iba1 was assessed through double-labeled immunofluorescence. The interaction between CysC and CTSB was investigated using double-labeled immunofluorescence and co-immunoprecipitation. The findings revealed an elevation of CysC expression level, particularly at 24h after ICH. Exogenous CysC supplementation alleviated severe brain edema, neurological deficit scores, and EB extravasation induced by ICH. Conversely, CysC knockdown produced opposite effects. The expression levels of CTSB and the NLRP3 inflammasome were significantly risen following ICH, and exogenous CysC supplement attenuated their expression levels. Double-labeled immunofluorescence illustrated that CysC, CTSB, and the NLRP3 inflammasome were predominantly expressed in microglial cells, and the interaction between CysC and CTSB was evidenced. CysC exhibited potential in ameliorating SBI following ICH via effectively suppressing the activation of the NLRP3 inflammasome mediated by CTSB specifically in microglial cells. These findings underscore the prospective therapeutic efficacy of CysC in the treatment of ICH-induced complications.

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol.

Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age. We studied how sex and age impact HE and its severity with combined liver toxins. Our findings indicate that drug-induced (thioacetamide, TAA) brain edema was more severe in aged males than in young males or young/aged female rats. However, adding alcohol (ethanol, EtOH) worsens TAA's brain edema in both young and aged females, with females experiencing a more severe effect than males. These patterns also apply to Type A HE induced by azoxymethane (AZO) in mice. Similarly, TAA-induced behavioral deficits in Type C HE were milder in young and aged females than in males. Conversely, EtOH and TAA in young/aged males led to severe brain edema and fatality without noticeable behavioral changes. TAA metabolism was slower in aged males than in young or middle-aged rats. When TAA-treated aged male rats received EtOH, there was a slow and sustained plasma level of thioacetamide sulfoxide (TASO). This suggests that with EtOH, TAA-induced HE is more severe in aged males. TAA metabolism was similar in young, middle-aged, and aged female rats. However, with EtOH, young and aged females experience more severe drug-induced HE as compared to middle-aged adult rats. These findings strongly suggest that gender and age play a role in the severity of HE development and that the presence of one or more liver toxins may aggravate the severity of the disease progression.

Use of biomarkers for predicting a malignant course in acute ischemic stroke: an observational case–control study

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers—S100B protein, MMP-9, and IL-10—were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke.

311: SEVERE HYPERAMMONEMIA CAUSED BY CARNITINE DEFICIENCY DURING ADULTHOOD

Introduction: Carnitine is a necessary co-factor in the oxidation of fatty acids as part of the urea cycle; deficiency of which may lead to heart or liver failure. Primary carnitine deficiency due to transporter defects or mutations is seen in infants. Secondary carnitine deficiency is the result of whole-body carnitine deficiency. Here, we discuss a case of secondary deficiency due to vegetarianism, leading to severe hyperammonemia. Description: A 23-year-old woman was admitted with one day of vomiting and diarrhea. On arrival, she was confused but alert, though rapidly decompensated and developed obtundation, clonus, rigidity, posturing, and non-reactive mydriatic pupils, requiring emergent intubation. Work-up was significant for elevated ammonia to 581 umol/L with CT head showing severe brain edema prompting placement of external ventricular drain for intracranial hypertension and frequent hypertonic saline administration. Given significant hyperammonemia with otherwise negative work-up, the patient’s presentation was concerning for a urea cycle defect. The patient was dialyzed and started on arginine, sodium benzoate/phenylacetate, citrulline, and buphenyl. Further history revealed a diet devoid of meat. Plasma amino acid analysis revealed decreased total carnitine 3 umol/L (27-73) and free carnitine 2 umol/L (20-55). There were no mutations in the carnitine transport gene or deficient enzymatic activity for the urea cycle. After one week, she was awake, alert, and was extubated shortly thereafter. Once tolerating oral intake, her diet of was supplemented with oral carnitine. She was able to make a full recovery and return home without deficits from baseline prior to admission. Discussion: Common causes of hyperammonemia are hepatic failure, genetic urea cycle defects, and organic academies, which were ruled out in this case. Carnitine is an important co-factor in the metabolism of long-chain fatty acids and its disruption impairs ammonia excretion through inhibition of the urea cycle. Secondary carnitine deficiency is seen in severe malnutrition, and causes hyperammonemia and encephalopathy. This case is particularly important to note, as fatty acid oxidation disorders based on pure dietary deficiency that presents during adulthood are uncommon and not frequently considered in the differentials.

Association Between Post-procedure Cerebral Blood Flow Velocity and Severity of Brain Edema in Acute Ischemic Stroke With Early Endovascular Therapy.

ObjectivesWe aimed to investigate the association between post-procedure cerebral blood flow velocity (CBFV) and severity of brain edema in patients with acute ischemic stroke (AIS) who received early endovascular therapy (EVT).MethodsWe retrospectively included patients with AIS who received EVT within 24 h of onset between February 2016 and November 2021. Post-procedure CBFV of the middle cerebral artery was measured in the affected and the contralateral hemispheres using transcranial Doppler ultrasound. The severity of brain edema was measured using the three-level cerebral edema grading from the Safe Implementation of Thrombolysis in Stroke-Monitoring Study, with grades 2–3 indicating severe brain edema. The Association between CBFV parameters and severity of brain edema was analyzed.ResultsA total of 101 patients (mean age 64.2 years, 65.3% male) were included, of whom 56.3% (57/101) suffered brain edema [grade 1, 23 (22.8%); grade 2, 10 (9.9%); and grade 3, 24 (23.8%)]. Compared to patients with non-severe brain edema, patients with severe brain edema had lower affected/contralateral ratios of systolic CBFV (median 1 vs. 1.2, P = 0.020) and mean CBFV (median 0.9 vs. 1.3, P = 0.029). Multivariate logistic regression showed that severe brain edema was independently associated with affected/contralateral ratios of systolic CBFV [odds ratio (OR) = 0.289, 95% confidence interval (CI): 0.069–0.861, P = 0.028] and mean CBFV (OR = 0.278, 95% CI: 0.084–0.914, P = 0.035) after adjusting for potential confounders.ConclusionPost-procedure affected/contralateral ratio of CBFV may be a promising predictor of brain edema severity in patients with AIS who received early EVT.

Efficacy and safety of fibrinogen administration in acute post-traumatic hypofibrinogenemia in isolated severe traumatic brain injury: A randomized clinical trial

AimThis study was conducted to evaluate clinical outcomes after fibrinogen administration in hypofibrinogenemia following severe traumatic brain injury. BackgroundPost traumatic coagulopathy (PTC) is a common but devastating medical condition in patients with severe head injury. Hypofibrinogenemia is considered as an indicator for poor clinical outcomes in traumatic brain injury (TBI). MethodsIn this randomized clinical trial (RCT), primarily 137 patients with severe traumatic brain injury (Glasgow coma scale score: GCS < 9) were enrolled. Thereafter, their plasma fibrinogen level was measured. The patients with primary hypofibrinogenemia (<200 mg/dL) with no concurrent coagulopathy were randomly allocated into fibrinogen-receiving (n = 50) and control (n = 54) groups. P-value < 0.05 was considered as statistically significant. ResultsSeventy-one patients were analyzed in the final step of the study. The mean value for age in fibrinogen and control groups was 25.64 ± 10.71 and 28.91 ± 12.25 years old, respectively. Male – female patients in both groups were equally distributed. In the fibrinogen receiving group, GCS scores were significantly higher after 24, 48, and 72 h compared to the control group (p = 0.000). Hematoma expansion was better controlled in the fibrinogen receiving group (p = 0.000). Notably, the number needed to treat (NNT) for fibrinogen infusion and hematoma expansion control was 2.3. Glasgow outcome scale-extended (GOSE) was significantly better in the fibrinogen group (p = 0.25). Multiple regression tests showed intracerebral hematoma (ICH) and severe brain edema had the most detrimental effect on GOSE outcomes. The need for cranial surgery, hospital stay duration, mechanical ventilator dependency, in hospital and 90-day post discharge mortality rates were similar in both study groups. ConclusionIn severe TBI, hypofibrinogenemia correction (>200 mg/dL) could improve GOSE, GCS score progression within 3 days after primary head injury and hematoma expansion controllability.

Usefulness of Self-Expandable Stent for Recanalization of Intracranial Atherosclerotic Disease: Preliminary Experience with Enterprise Stent.

PurposeThe purpose of this preliminary study is to evaluate the efficacy and safety of the Enterprise stent for intracranial atherosclerotic disease (ICAD) in patients who presented with acute stroke due to vessel steno-occlusion and in patients with symptomatic disease despite optimum medical management.Materials and MethodsA retrospective data analysis was performed on 15 consecutive patients who were treated with Enterprise stenting for recanalization of symptomatic intracranial steno-occlusive arteries due to underlying ICAD. Their clinical and radiological data were reviewed to evaluate procedural results, periprocedural and postprocedural complications, and clinical outcome.ResultsEnterprise stents were deployed as a rescue method in 15 patients for recanalization of steno-occlusion. All patients achieved final modified thrombolysis in cerebral infarction (mTICI) score improvement (53.3% with a mTICI score from 0 to 2b or 3, 46.7% with a mTICI score from 1 to 3). Two postprocedural complications (1 symptomatic intracranial hemorrhage and 1 severe brain edema, 13.3%) occurred among 15 patients. Among 12 patients with acute ischemic stroke (AIS), 6 patients (50%) had improvement in their National Institute of Health Stroke Scale of more than 4 at discharge. Seven patients (58.3%) had a good functional outcome with 3-month modified Rankin Score (mRS)≤2, and mortality occurred (mRS=6) in 2 patients (16.7%). None of the 10 AIS and 3 transient ischemic attack patients experienced further ischemic events attributable to the treated steno-occlusion during the follow-up period (ranged from 4 to 36 months, median 12 months).ConclusionThis retrospective study suggests that Enterprise stenting can effectively and safely achieve recanalization in symptomatic steno-occlusive intracranial arteries.

Analysis of a Novel Entry Point for Freehand Ventriculostomy Using Computerized Tomography Scans.

BackgroundExternal ventricular drain (EVD) placement is one of the most common procedures in neurosurgery. Neurosurgeons generally prefer to access the ventricles via Kocher’s point since it is the most common point of entry to this area; however, this point is used to describe different anatomic landmarks and is not well-defined.ObjectiveThe present study aims to describe and provide an anatomical assessment of a novel ventriculostomy access point developed by the authors using computerized tomography (CT) scans performed on 100 patients.Materials and methodsData were collected from 100 randomly selected patients with normal ventricular anatomy found on their 1.0 mm-slice CT scans performed at the Burdenko Neurosurgical Center from March 2019 to June 2021. The CT inclusion criteria were: CT slices < or = to 1 mm and absence of brain herniation. Patients with brain mass lesions, severe brain edema, and pneumocephalus were excluded. Age, gender, and ventricular size were not exclusion criteria.ResultsThe mean patient age was 43.58 years (range 4-73), with 50 men and 50 women. The mean Evan’s index was 25.7 % (SD=4.38 %, range 10.2-41.0 %). No differences were found between the angles of EVD placement on either side (89.50±1.22 degrees on the right and 89.60±1.14 degrees on the left). Hence, nearly all EVD cases had been placed perpendicularly to the skull surface at a pinpoint location.ConclusionThe proposed point of successful ventriculostomy placement in this study was 3 cm from the bregma along the coronal suture. The angle of EVD placement was approximately 90 degrees in almost all patients and was independent of the patient’s age and the side of the head that was entered. Little correlation was found between the value of the entry angle and Evan’s index. The point is simply identifiable, and its entry is easily accessible in practice.

Nrf2 loss of function exacerbates endoplasmic reticulum stress-induced apoptosis in TBI mice

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in neuroprotection and recover. Our studies have showed that endoplasmic reticulum (ER) stress-induced apoptosis aggravates secondary damage following traumatic brain injury (TBI). Whether Nrf2 involved in ER stress and ER stress-mediated apoptosis is not clearly investigated. This present study explored the effect of Nrf2 knockout on ER stress and ER stress-induced apoptosis in TBI mice. A lateral fluid percussion injury (FPI)model of TBI was built based on Nrf2 knockout (Nrf2(−/−)) mice and wild-type (Nrf2(+/+)) mice, and the expressions of marker proteins of ER stress and ER stress-induced apoptosis were checked at 24 h following TBI. We found that Nrf2(−/−) mice presented more severe neurological deficit, brain edema and neuronal cell apoptosis compared with Nrf2(+/+) mice. And, the TBI Nrf2(−/−) mice were significantly increased expression of marker proteins of ER stress and ER stress-induced apoptotic pathway including glucose regulated protein (GRP78), protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme (IRE1), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), caspase-12 and caspase-3, compared with that in WT mice. These results suggest that Nrf2 could ameliorate TBI-induced second brain injury partly through ER stress signal pathway.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior–superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.

An autopsy case of unexpected death due to Addison\u2019s disease caused by adrenal tuberculosis

BackgroundAdrenal tuberculosis is difficult to diagnose due to non-specific symptom. Unexpected death due to adrenal insufficiency after trauma surgery is rare.Case presentationA 45-year-old man, who was admitted to hospital because of trauma to the right hand, died unexpectedly on the 13th day after replantation of amputated fingers. He was diagnosed with brain edema and diluted hyponatremia. Autopsy and histopathologic examination revealed severe brain edema combined with cerebellar tonsillar hernia, extensive destruction of adrenal gland caused by bilateral adrenal tuberculosis and right lung invasive pulmonary tuberculosis.ConclusionsTrauma and pulmonary tuberculosis complicated with adrenal tuberculosis induced the adrenal crisis, which eventually lead to severe cerebral edema and hernia, and finally death from respiratory and circulatory failure. This autopsy and histopathologic examination suggested a possible pathophysiologic mechanism of sudden death due to diluted hyponatremia after trauma surgery.

Abstract 9899: Sex-Related Differences in Severe Cerebral Edema Development in Comatose Cardiac Arrest Patients

Introduction: Previous studies have shown that women have poorer neurological outcomes than men following out-of-hospital cardiac arrest (OHCA). However, those studies focused on survival, a measure that may be confounded by withdrawal of life-sustaining therapy (WLST) decisions. We sought to assess sex differences in severe cerebral edema development following cardiac arrest. Methods: Data from adult OHCA patients presenting between 2007-2019 were retrospectively analyzed. Patients with multiple concomitant acute neurologic dysfunctions were excluded. Severe cerebral edema was classified as herniation or more than minimal ventricular effacement in MRI or CT radiology reports. Arrest types were categorized as shockable (VT/VF) or non-shockable (PEA, asystole). Poor outcomes were defined as Cerebral Performance Category &gt; 3 at discharge. Multivariable backward stepwise logistic regression was performed. Results: 359 patients met our inclusion criteria. Demographics, imaging and clinical outcomes are summarized in Table 1. Women were more likely than men to have a non-shockable initial rhythm (P=0.003) and develop severe cerebral edema (P=0.005). Backwards stepwise logistic regression of an initial model including age, sex, rhythm, witnessed arrest and TTM-treatment, produced a final model that showed younger age (P&lt;0.001), female sex (P=0.01), and non-shockable rhythm (P&lt;0.001) as significant predictors of severe cerebral edema development. Patients with severe cerebral edema had worse outcomes (89/91 vs 176/268, P&lt;0.001), and greater in-hospital mortality (82/91 vs 166/268, P&lt;0.001), with a higher proportion of deaths due to brain death (15/82 vs 3/166 P&lt;0.001). Conclusion: For OHCA patients who are initially comatose, women are more likely than men to have non-shockable rhythms and severe cerebral brain edema. These differences may be responsible for the poorer discharge outcomes that have been observed by other studies.

Multiple Brain Abscesses by an Air Gun Shot: A Case Report

Abstract Introduction Low-velocity penetrating brain injury is not prevalent. In some conditions such as childhood, and with the penetration of a pellet in weak spots of skull, low-velocity penetrating brain injury is expected; however, high-velocity projectiles have also been reported as the cause of severe brain injuries. One of the complications of penetrating brain injury is infection, in which different types of microorganisms play a role. The Streptococcus genus is the leading cause of abscess formation in non-traumatic patients. Multiple brain abscesses are not common. Case Presentation A 10-year-old boy with penetrating brain injury caused by an air gun pellet, who developed signs and symptoms of high intracranial pressure 18 days after the trauma. After the imaging scans and the detection of multiple brain abscesses and severe brain edema, prompt surgical intervention was performed for all three lesions in a single operation. The culture of a pus specimen was positive for Streptococcus species, and, with adequate antibiotic therapy, the patient was discharged from the hospital in good condition. Conclusion Brain injury with air gun shot is not prevalent. The penetration of a low-velocity air gun pellet in weak points of the skull (such as the orbit, the squamous portion of the temporal bone, and the cranial suture), specially in children, can cause significant brain injuries.

Impaired meningeal lymphatic vessels exacerbate early brain injury after experimental subarachnoid hemorrhage

Background and purposeBlood that enters the subarachnoid space (SAS) and its breakdown products are neurotoxic and are the principal inducers of brain injury after subarachnoid hemorrhage (SAH). Recently, meningeal lymphatic vessels (MLVs) have been proven to play an important role in clearing erythrocytes that arise from SAH, as well as other macromolecular solutes. However, evidence demonstrating the relationship between MLVs and brain injury after SAH is still limited. Therefore, we performed this study to observe the effects of meningeal lymphatic impairment on early brain injury (EBI) after experimental SAH. MethodsThe MLVs of C57BL/6 male adult mice were ablated by injecting Visudyne into the cisterna magna and transcranially photoconverting it with laser light. The MLVs were then examined by immunofluorescence staining for lyve-1. Next, both the MLV-ablated group and the control group (normal mice) underwent filament perforation to model SAH or sham operation. We assessed the cortical perfusion of all the mice before SAH induction, 5 min after SAH and 24 h after SAH. In addition, we evaluated neurological function deficits by Garcia scores and measured brain water content at 24 h post SAH. Then, neuroinflammation and neural apoptosis in the mouse brain were also examined. ResultsVisudyne and transcranial photoconversion treatment notably ablated mouse MLVs. Five minutes after SAH induction, cortical perfusion was significantly impaired, and after 24 h, this impairment was ameliorated considerably in the control group but ameliorated only slightly or worsened in the MLV-ablated group. Additionally, the MLVablated group presented worse neurological function deficits and more severe brain edema than the control group. More notably, neuroinflammation and neural apoptosis were also observed. ConclusionAblation of MLVs by Visudyne treatment exacerbated EBI after experimental SAH in mice. The worsening of EBI may have arisen from limited drainage of blood and other breakdown products, which are thought to cause brain edema, neuroinflammation, neuronal apoptosis and other pathological processes.

Retinoic acid exerts neuroprotective effects against focal cerebral ischemia by preventing apoptotic cell death

Cerebral ischemia is a neurological disorder that leads to cognitive decline and high mortality. Retinoic acid is a metabolite of vitamin A that has anti-inflammatory and anti-apoptotic effects. This study investigated whether retinoic acid prevents neuronal cell damage on focal cerebral ischemia through modulating apoptosis signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia in adult male rats. Retinoic acid (5 mg/kg) or vehicle was injected intraperitoneally for 4 days prior to MCAO. Neurological behavior deficit tests were performed 24 h after MCAO. Brain edema and infarct volume were measured, and TUNEL histochemistry was carried out. We also investigated the changes in apoptosis-related proteins including bcl-2 family proteins and caspases. MCAO injury induced severe neurological behavior deficits and brain edema. It also increased infarct volume, histopathological damages, and the number of TUNEL-positive cells in cerebral cortex. However, retinoic acid pretreatment attenuated MCAO-induced neurological behavior deficits, brain edema, and infarction. It also alleviated histopathological lesion and decreased the number of TUNEL-positive cells. Bcl-2 and bax proteins are representative bcl-2 family proteins. MCAO injury induced a decrease in bcl-2 expression and an increase in bax expression, and retinoic acid pretreatment alleviated these changes. MCAO injury caused a decrease in bcl-2/bax expression ratio in cerebral cortex, while retinoic acid restored this decrease by MCAO. Moreover, our result showed increases in caspase-9, caspase-3, PARP protein levels in MCAO-operated animals. Retinoic acid pretreatment prevented these increases. We identified the changes in cleaved forms of these proteins, similar to the changes in full-length protein. Activation of caspases and PARP proteins are considered to be representative apoptosis indicators. This study showed that retinoic acid regulates bcl-2 family proteins and caspase proteins in focal cerebral ischemia. Thus, our findings demonstrate that retinoic acid exhibits a neuroprotective effect against ischemic damage by modulating apoptosis signaling pathway.

Pseudo-SAH in a patient with methanol poisoning

Objective: Methanol poisoning is a dangerous life-threatening event, manifested with various symptoms, sometimes very rare ones, that all should be addressed to prevent misdiagnosis of the methanol-poisoned patients. Case Presentation: A 21-year-old young man was brought to the emergency department (ED) with a generalized tonic-clonic (GTC) seizure and he was diagnosed with methanol intoxication. A non-contrast computed tomography (NCCT) of the brain demonstrated findings similar to subarachnoid hemorrhage (SAH). After the brain CT, he had a Glasgow Coma Score (GCS) of 3 and all brainstem reflexes were absent. Neurology consultant agreed with the diagnosis of pseudo-SAH. Brain death was confirmed by a positive apnea test within 24 hours of presentation. Conclusion: It is suggested that compression of dural sinuses due to severe brain edema, reduces the venous drainage and leads to venous engorgement, which appears high attenuated in the background of low-density edematous brain matter.

Prognostic Factors for Pediatric Acute Encephalopathy Associated with Severe Brain Edema

Background and Objective: Acute encephalopathy is a life-threatening brain dysfunction in children, often associated with a preceding infection and diffuse noninflammatory brain edema. At present, the role of decompressive craniectomy (DC) over the swollen area of the brain is unclear. The risk factors for predicting clinical deterioration also need clarification. Methods: A retrospective study of pediatric patients admitted between 2015 and 2019 with acute cerebral encephalopathy was carried out. Patients were classified according to: (1) the preceding pathogens, (2) the syndromic classification, and (3) the extent of brain edema. The syndromic classification is a relatively new classification of acute encephalopathy proposed in 2016 and divides patients into 3 groups: those with systemic inflammatory reactions or “cytokine storms” (group 1), those with status epilepticus but no cytokine storm (group 2), and others (group 3). Glasgow Outcome Scale (GOS) scores of 1–3 were defined as unfavorable, while a GOS score of 4 or 5 was defined as a favorable outcome in this study. DC was performed for select patients with life-threatening signs of brainstem compression. Results: Nineteen patients (mean age: 23.3 months) were included in the study, 8 (42.1%) of whom had an unfavorable outcome. There was no significant correlation between the types of pathogens and outcome. Unfavorable outcomes were observed in significantly more patients in group 1 (87.5%) than group 2 (14.3%) and group 3 (0%). There was a significant association between diffuse brain edema and unfavorable outcomes (72.7%). Neurosurgical DC was performed in 2 patients to alleviate life-threatening brainstem compression: one with a cytokine storm and diffuse bilateral brain edema, and the other with prolonged status epilepticus causing diffuse right-sided brain edema. The GOS score was 3 and 4, respectively. Conclusion: The risk factors for clinical deterioration in pediatric acute encephalopathy were evaluated based on a variety of classifications, including the new syndromic classification. Laboratory features of cytokine storms and radiological evidence of diffuse brain edema were associated with unfavorable outcomes. The role of surgical decompression is still controversial and should be assessed on a case-by-case basis.

Osteopathic Manipulative Treatment to Optimize the Glymphatic Environment in Severe Traumatic Brain Injury Measured With Optic Nerve Sheath Diameter, Intracranial Pressure Monitoring, and Neurological Pupil Index.

BackgroundTraumatic brain injury (TBI) has a complex pathophysiology that has historically been poorly understood. New evidence on the pathophysiology, molecular biology, and diagnostic studies involved in TBI have shed new light on optimizing rehabilitation and recovery. The goal of this study was to assess the effect of osteopathic manipulative treatment (OMT) on peripheral and central glial lymphatics in patients with severe TBI, brain edema, and elevated intracranial pressure (ICP) by measuring changes in several parameters regularly used in management.MethodologyThis was a retrospective study at a level II trauma center that occurred in 2018. The study enrolled patients with TBI, increased ICP, or brain edema who had an external ventricular drain placed. Patients previously underwent a 51-minute treatment with OMT with an established protocol. Patients received 51 minutes of OMT to the head, neck, and peripheral lymphatics. The ICP, cerebrospinal fluid (CSF) drainage, optic nerve sheath diameter (ONSD) measured by ultrasonography, and Neurological Pupil Index (NPi) measured by pupillometer were recorded before, during, and after receiving OMT.ResultsA total of 11 patients were included in the study, and 21 points of data were collected from the patients meeting inclusion criteria who received OMT. There was a mean decrease in the ONSD of 0.62 mm from 6.24 mm to 5.62 mm (P = 0.0001). The mean increase in NPi was 0.18 (P = 0.01). The mean decrease in ICP was 3.33 mmHg (P= 0.0001). There was a significant decrease in CSF output after treatment (P = 0.0001). Each measurement of ICP, ONSD, and NPi demonstrated a decrease in overall CSF volume and pressure after OMT compared to CSF output and ICP prior to OMT.ConclusionsThis study demonstrates that OMT may help optimize glial lymphatic clearance of CSF and improve brain edema, interstitial waste product removal, NPi, ICP, CSF volume, and ONSD. A holistic approach including OMT may be considered to enhance management in TBI patients. As TBI is a spectrum of disease, utilizing similar techniques may be considered for all forms of TBI including concussions and other diseases with brain edema. The results of this study can better inform future trials to specifically study the effectiveness of OMT in post-concussive treatment and in those with mild-to-moderate TBI.

Microglia-derived interleukin-10 accelerates post-intracerebral hemorrhage hematoma clearance by regulating CD36

Hematoma size after intracerebral hemorrhage (ICH) significantly affects patient outcome. However, our knowledge of endogenous mechanisms that underlie hematoma clearance and the potential role of the anti-inflammatory cytokine interleukin-10 (IL-10) is limited. Using organotypic hippocampal slice cultures and a collagenase-induced ICH mouse model, we investigated the role of microglial IL-10 in phagocytosis ex vivo and hematoma clearance in vivo. In slice culture, exposure to hemoglobin induced IL-10 expression in microglia and enhanced phagocytosis that depended on IL-10–regulated expression of CD36. Following ICH, IL-10–deficient mice had more severe neuroinflammation, brain edema, iron deposition, and neurologic deficits associated with delayed hematoma clearance. Intranasal administration of recombinant IL-10 accelerated hematoma clearance and improved neurologic function. Additionally, IL-10–deficient mice had weakened in vivo phagocytic ability owing to decreased expression of microglial CD36. Moreover, loss of IL-10 significantly increased monocyte-derived macrophage infiltration and enhanced brain inflammation in vivo. These results indicate that IL-10 regulates microglial phagocytosis and monocyte-derived macrophage infiltration after ICH and that CD36 is a key phagocytosis effector regulated by IL-10. Leveraging the innate immune response to ICH by augmenting IL-10 signaling may provide a useful strategy for accelerating hematoma clearance and improving neurologic outcome in clinical translation studies.