Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke.

BACKGROUND: Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect. METHODS: We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates. We assessed trajectories of the 10 longitudinal variables during the 72 h preceding three outcomes representative of life-threatening mass effect: midline shift ≥ 5 mm, pineal gland shift (PGS) > 4 mm, and decompressive hemicraniectomy (DHC). We used a "backward-looking" trajectory approach. Patients were aligned based on outcome occurrence time and the trajectory of each variable was assessed before that outcome by accounting for cases and noncases, adjusting for confounders. We evaluated longitudinal trajectories with Cox proportional time-dependent regression. RESULTS: Of 635 patients, 49.0% were female, and the mean age was 69 years. Thirty five percent of patients had midline shift ≥ 5 mm, 24.3% of patients had PGS > 4 mm, and 10.7% of patients underwent DHC. Backward-looking trajectories showed mild increases in white blood cell count (10-11 K/UL within 72 h), temperature (up to half a degree within 24 h), and sodium levels (1-3 mEq/L within 24 h) before the three outcomes of interest. We also observed a decrease in heart rate (75-65 beats per minute) 24 h before DHC. We found a significant association between increased white blood cell count with PGS > 4 mm (hazard ratio 1.05, p value 0.007). CONCLUSIONS: Longitudinal profiling adjusted for confounders demonstrated that white blood cell count, temperature, and sodium levels appear to increase before radiographic and clinical indicators of space-occupying mass effect. These findings will inform the development of multivariable dynamic risk models to aid prediction of life-threatening, space-occupying mass effect.

Exploration of the Molecular Mechanism by Which Caveolin-1 Regulates Changes in Blood-Brain Barrier Permeability Leading to Eosinophilic Meningoencephalitis.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Multimodal neuroimaging exploration of the mechanisms of sleep quality deterioration after SARS-CoV-2 Omicron infection.

BACKGROUND: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. METHODS: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. RESULTS: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = - 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = - 0.406, P = 0.026, PFDR = 0.026) scores. CONCLUSIONS: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.

The role of oxidative stress and neuroinflammatory mediators in the pathogenesis of high-altitude cerebral edema in rats.

High-altitude environments present extreme conditions characterized by low barometric pressure and oxygen deficiency, which can disrupt brain functioning and cause edema formation. The objective of the present study is to investigate several biomolecule expressions and their role in the development of High Altitude Cerebral Edema in a rat model. Specifically, the study focuses on analyzing the changes in total arginase, nitric oxide, and lipid peroxidation (MDA) levels in the brain following acute hypobaric hypoxic exposure (7620 m, SO2=8.1 %, for 24 h) along with the histopathological assessment. The histological examination revealed increased TNF-α activity, and an elevated number of mast cells in the brain, mainly in the hippocampus and cerebral cortex. The research findings demonstrated that acute hypobaric hypoxic causes increased levels of apoptotic cells, shrinkage, and swelling of neurons, accompanied by the formation of protein aggregation in the brain parenchyma. Additionally, the level of nitric oxide and MDA was found to have increased (p<0.0001), however, the level of arginase decreased indicating active lipid peroxidation and redox imbalance in the brain. This study provides insights into the pathogenesis of HACE by evaluating some biomolecules that play a pivotal role in the inflammatory response and the redox landscape in the brain. The findings could have significant implications for understanding the neuronal dysfunction and the pathological mechanisms underlying HACE development.

White Matter Hyperintensity is Associated with Malignant Cerebral Edema in Ischemic Stroke Treated with Thrombectomy.

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema.

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5'-monophosphate, deoxyguanosine 5'-monophosphate, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5'-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Importance of 1H-MR spectroscopy of the brain to identify the minimal hepatic encephalopathy in different patients with liver cirrhosis: A prospective study.

Objectives: Liver cirrhosis patients commonly progress to minimal hepatic encephalopathy (MHE) with cognitive impairment and raised blood ammonia and proinflammatory cytokines levels. This study aims to identify the subjects of MHE in patients with liver cirrhosis by hydrogen 1 magnetic resonance (1H-MR) spectroscopy of the brain, serum proinflammatory cytokines, and neuropsychiatric tests. Materials and Methods: This prospective was carried out on 100 patients of liver cirrhosis without overt hepatic encephalopathy (HE) and compared with 100 healthy controls in a tertiary care hospital in Northeast India between September 2017 and October 2019. The psychometric hepatic encephalopathy score (PHES) neuropsychological tests, cranial MRIwith 1H-MR spectroscopy, and estimation of serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were done. The PHES scores and serum proinflammatory markers levels were correlated with the conventional and 1H-MR spectroscopy findings of the brain. Results: The mean PHES score in the case group was -7.58±3.43 (standard deviation [SD]) and the control group was -3.41 ± 3.87 (SD). Patients with Child-Pugh class A (n = 8) had a PHES score of -8.7 ± 2.5 (SD), class B (n = 42) -7.62 ± 3.7 (SD), and class C (n = 50) had a score of -7.36 ± 3.3 (SD). The mean value of IL-6 and TNF-α in the case group was 219 ± 180 (SD) pg/mL and 99 ± 118 (SD) pg/mL and the control group was 67.4 ± 77 (SD) pg/mL and 57.5 ± 76 (SD) pg/mL. Globus pallidus T1-weighted hyperintensities on the visibility scale with a visibility score of 0 were observed in 39 cases, a score of 1 in 38 cases, and a score of 2 in 23 cases. Increased glutamate/glutamine/creatine (Glx/Cr) ratio was identified in the case group on MR spectroscopy as compared to the control (0.95 ± 0.24 vs. 0.31 ± 0.19, P < 0.0005), a decrease of myoinositol/creatine (mI/Cr) ratio (0.11 ± 0.13 vs. 0.30 ± 0.12, P < 0.0005), and increase choline/creatine (Cho/Cr) ratio (0.69 ± 0.26 vs. 0.61 ± 0.20, P < 0.0005). There was a statistically significant difference in Glx/Cr, mI/Cr and Cho/Cr ratio between the case and control groups with P < 0.0005. Conclusion: Predicting the development of MHE in established cases of liver cirrhosis using non-invasive modalities like PHES, IL-6, TNF-α levels, and 1H-MR spectroscopy plays an important role in further progression to overt HE and coma.

Lymphatic network drainage resolves cerebral edema and facilitates recovery from experimental cerebral malaria.

While brain swelling, associated with fluid accumulation, is a known feature of pediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain during recovery from CM is unknown. Using the experimental CM (ECM) model, we show that fluid accumulation in the brain during CM is driven by vasogenic edema and not by perivascular cerebrospinal fluid (CSF) influx. We identify that fluid and molecules are removed from the brain extremely quickly in mice with ECM to the deep cervical lymph nodes (dcLNs), predominantly through basal routes and across the cribriform plate and the nasal lymphatics. In agreement, we demonstrate that ligation of the afferent lymphatic vessels draining to the dcLNs significantly impairs fluid drainage from the brain and lowers anti-malarial drug recovery from the ECM syndrome. Collectively, our results provide insight into the pathways that coordinate recovery from CM.

New Insights on Mechanisms and Therapeutic Targets of Cerebral Edema.

Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.

Later Midline Shift Is Associated with Better Outcomes after Large Middle Cerebral Artery Stroke.

Background/Objective: Space occupying cerebral edema is the most feared early complication after large ischemic stroke, occurring in up to 30% of patients with middle cerebral artery (MCA) occlusion, and is reported to peak 2-4 days after injury. Little is known about the factors and outcomes associated with peak edema timing, especially when it occurs after 96 hours. We aimed to characterize differences between patients who experienced maximum midline shift (MLS) or decompressive hemicraniectomy (DHC) in the acute (<48 hours), average (48-96 hours), and subacute (>96 hours) groups and determine whether patients with subacute peak edema timing have improved discharge dispositions. Methods: We performed a two-center, retrospective study of patients with ≥1/2 MCA territory infarct and MLS. We constructed a multivariable model to test the association of subacute peak edema and favorable discharge disposition, adjusting for age, admission Alberta Stroke Program Early CT Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS), acute thrombolytic intervention, cerebral atrophy, maximum MLS, parenchymal hemorrhagic transformation, DHC, and osmotic therapy receipt. Results: Of 321 eligible patients with MLS, 32%, 36%, and 32% experienced acute, average, and subacute peak edema. Subacute peak edema was significantly associated with higher odds of favorable discharge than non-subacute swelling, adjusting for confounders (aOR, 1.85; 95% CI, 1.05-3.31). Conclusions: Subacute peak edema after large MCA stroke is associated with better discharge disposition compared to earlier peak edema courses. Understanding how the timing of cerebral edema affects risk of unfavorable discharge has important implications for treatment decisions and prognostication.

Astrocyte modulation in cerebral ischemia-reperfusion injury: A promising therapeutic strategy.

Cerebral ischemia-reperfusion injury (CIRI) poses significant challenges for drug development due to its complex pathogenesis. Astrocyte involvement in CIRI pathogenesis has led to the development of novel astrocyte-targeting drug strategies. To comprehensively review the current literature, we conducted a thorough analysis from January 2012 to December 2023, identifying 82 drugs aimed at preventing and treating CIRI. These drugs target astrocytes to exert potential benefits in CIRI, and their primary actions include modulation of relevant signaling pathways to inhibit neuroinflammation and oxidative stress, reduce cerebral edema, restore blood-brain barrier integrity, suppress excitotoxicity, and regulate autophagy. Notably, active components from traditional Chinese medicines (TCM) such as Salvia miltiorrhiza, Ginkgo, and Ginseng exhibit these important pharmacological properties and show promise in the treatment of CIRI. This review highlights the potential of astrocyte-targeted drugs to ameliorate CIRI and categorizes them based on their mechanisms of action, underscoring their therapeutic potential in targeting astrocytes.

A case report of leukemoid reaction in a child with severe diabetic ketoacidosis (DKA) and cerebral edema: When rarity and complexity meet.

Key Clinical Message: In pediatrics, a leukemoid reaction in severe DKA cases with cerebral edema has never been reported. The fluid management was challenging as it required balancing rates to ensure improvement of the condition while preventing neurological sequelae. Abstract: The combination of diabetic ketoacidosis (DKA), cerebral edema, and leukemoid reaction in pediatrics has never been reported before in the literature. It may lead to significant morbidity and high mortality. Here, we report a case of DKA-induced cerebral edema associated with severe leukocytosis (WBC 98 × 109/L), which had many challenges in fluid therapy.

Critical care management of acute liver failure.

The management of acute liver failure (ALF) in modern hepatology intensive care units (ICU) has improved patient outcomes. Critical care management of hepatic encephalopathy, cerebral edema, fluid and electrolytes; prevention of infections and organ support are central to improved outcomes of ALF. In particular, the pathogenesis of encephalopathy is multifactorial, with ammonia, elevated intra-cranial pressure and systemic inflammation playing a central role. Although ALF remains associated with high mortality, the availability of supportive care, including organ failure support such as plasma exchange, timely mechanical ventilation or continuous renal replacement therapy, either conservatively manages patients with ALF or offers bridging therapy until liver transplantation. Thus, appropriate critical care management has improved the likelihood of patient recovery in ALF. ICU care interventions such as monitoring of cerebral edema, fluid status assessment and interventions for sepsis prevention, nutritional support and management of electrolytes can salvage a substantial proportion of patients. In this review, we discuss the key aspects of critical care management of ALF.

Oral Glyburide for the Prevention of Cerebral Edema in Acute Ischemic Stroke.

OBJECTIVE: The purpose of this study was to describe the impact of enteral glyburide on cerebral edema formation and hypoglycemia when used to treat patients diagnosed with acute ischemic stroke (AIS). METHODS: This study was a single-center, retrospective medical record review that included all patients aged ≥18 years diagnosed with AIS who received ≥1 dose of enteral glyburide for the prevention of cerebral edema from January 1, 2018 to March 31, 2022. The primary outcome was the percentage of patients requiring intervention for cerebral edema management after glyburide initiation, and the safety outcome was the occurrence of hypoglycemia in this patient population. RESULTS: The final evaluation included 44 patients, with 6 patients (14%) requiring intervention for cerebral edema after glyburide initiation. The average baseline National Institutes of Health stroke scale score was 19. Overall, in-hospital mortality was 36% (n = 17), and hypoglycemia occurred in 7 patients (15%). Of the 44 patients, 20 (45%) received a partial duration of enteral glyburide (1-4 doses) and 24 (55%) received a full duration of enteral glyburide (5-7 doses). The rate of intervention for cerebral edema (10% vs. 17%) and the incidence of hypoglycemia (5% vs. 23%) were lower in the partial duration than in the full duration group. The in-hospital all-cause mortality rate was higher in the partial duration group than in the full duration group (43% vs. 31%). CONCLUSIONS: Despite the relatively low rates of intervention for cerebral edema, hypoglycemia was common, especially for patients receiving 5-7 doses of enteral glyburide for the prevention of cerebral edema after moderate-to-severe AIS.

Effect of butylphthalide on prevention and treatment of high altitude cerebral edema in rats.

3-n-butylphthalide (NBP) contains one of the main active ingredients of celery seed. It has a series of pharmacological mechanisms, including reconstitution of microcirculation, protection of mitochondrial function, inhibition of oxidative stress, and inhibition of neuronal apoptosis. Based on the complex multi-targeting of NBP pharmacological mechanisms, the clinical applications of NBP are increasing, and more and more clinical studies and animal experiments have focused on NBP. In this study, we used male Sprague Dawley rats as an animal model to elucidate the intervention effect of butylphthalide on high altitude cerebral edema (HACE), and also compared the effect of butylphthalide and rhodiola rosea on HACE. Firstly, we measured the changes of body weight and brain water content and observed the pathological changes of brain tissues. In addition, the contents of inflammatory factors, oxidative stress and brain neurotransmitters were assessed by enzyme-linked immunoassay kits, and finally, the expression of apoptotic proteins in brain tissues was determined by western blotting. The results showed that NBP reduced brain water content, attenuated brain tissue damage, altered inflammatory factors, oxidative stress indicators, and brain neurotransmitter levels, and in addition NBP inhibited the expression of Caspase-related apoptotic proteins. Therefore, NBP has the potential to treat and prevent HACE.

Incidence, predictors, and outcomes of malignant cerebral edema in acute basilar artery occlusion after endovascular treatment: a secondary analysis of the ATTENTION trial.

OBJECTIVE: Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT. METHODS: This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis. RESULTS: A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up. CONCLUSIONS: MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.

Pattern Clustering of Symmetric Regional Cerebral Edema on Brain MRI in Patients with Hepatic Encephalopathy.

Purpose: Metabolic abnormalities in hepatic encephalopathy (HE) cause brain edema or demyelinating disease, resulting in symmetric regional cerebral edema (SRCE) on MRI. This study aimed to investigate the usefulness of the clustering analysis of SRCE in predicting the development of brain failure. Materials and Methods: MR findings and clinical data of 98 consecutive patients with HE were retrospectively analyzed. The correlation between the 12 regions of SRCE was calculated using the phi (Φ) coefficient, and the pattern was classified using hierarchical clustering using the φ2 distance measure and Ward's method. The classified patterns of SRCE were correlated with clinical parameters such as the model for end-stage liver disease (MELD) score and HE grade. Results: Significant associations were found between 22 pairs of regions of interest, including the red nucleus and corpus callosum (Φ = 0.81, p < 0.001), crus cerebri and red nucleus (Φ = 0.72, p < 0.001), and red nucleus and dentate nucleus (Φ = 0.66, p < 0.001). After hierarchical clustering, 24 cases were classified into Group I, 35 into Group II, and 39 into Group III. Group III had a higher MELD score (p = 0.04) and HE grade (p = 0.002) than Group I. Conclusion: Our study demonstrates that the SRCE patterns can be useful in predicting hepatic preservation and the occurrence of cerebral failure in HE.

Association of Serum Macrophage Migration Inhibitory Factor with 3-Month Poor Outcome and Malignant Cerebral Edema in Patients with Large Hemispheric Infarction.

BACKGROUND: We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). METHODS: Patients with LHI within 24 h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5 mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. RESULTS: Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82 ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56 ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). CONCLUSIONS: Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.

Evaluation of the Safety of Slow IV Push Versus Slow IV Infusion Administration of 23.4% Sodium Chloride.

Background and Purpose: Increased intracranial pressure due to cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Currently, safety data is limited on slow IV push (IVP) administration. The purpose of this study was to evaluate the safety of IVP administration of 23.4% NaCl and determine the number of infusion-related adverse events (IRAEs) compared to slow IV infusion (SIV) administration. Methods: We performed a retrospective review of patients who received a dose of 23.4% NaCl at the (removed institution) from January 2015 to June 2020 as either SIV over 30 minutes or IVP over 2-5 minutes. Results: In total, 81 patients, 55 in the IVP group and 26 in the SIV group, were included in the analysis. There was a significantly faster time from order entry to dose completion (IVP 25 [13,58] vs SIV 73 [55,113] minutes, P < .001). There was no difference in IRAEs between the groups (IVP 17 [31%] vs SIV 6 [23%], P = .466). Hypotension was most common (IVP 13 [24%] vs SIV 5 [19%], P = .656) followed by bradycardia (IVP 6 [11%] vs SIV 1 [4%], P = .291). There were no extravasations reported. Conclusions: Overall, among a cohort of patients with cerebral edema, we found no difference in the incidence of IRAEs between SIV and IVP administration of 23.4% NaCl, and found a faster time to complete administration fssor the latter. In emergent scenarios where time may impact neurologic function, 23.4% NaCl administered IVP may be an alternative to SIV administration.

The interplay of psychosis and non-compliance with fatal outcome in an adult with MSUD.

Significant progress has been achieved in enhancing early outcomes for individuals with maple syrup urine disease (MSUD), a rare metabolic disorder that leads to the accumulation of branched-chain amino acids leucine, isoleucine, and valine, where leucine is known as the primary neurotoxic metabolite. Newborn screening is helpful in early diagnosis and implementation of dietary treatment, thus reducing neurological deterioration and complications in young children. However, patients face the life-long challenge of maintaining metabolic control through adherence to a strict low-leucine diet to avoid long-term consequences of chronic hyperleucinemia, which include cognitive deficits, mood disorders, and movement disorders. This case report exemplifies the complex involvement of MSUD in adult survivors. Despite presenting early in life, the patient thrived until the onset of psychiatric symptoms. The subject of this case is a 25-year-old woman with MSUD, who remained in her usual state of health until presentation to the emergency department (ED) with psychosis and altered mental status. However, due to a lack of medical records and poor communication, there was a delay in considering MSUD as a primary cause of her psychiatric symptoms. Although a genetics consultation was later arranged and efforts were made to decrease plasma leucine to the therapeutic range, these interventions proved inadequate in halting her deterioration in health. Her condition worsened within 72 h, culminating in her untimely death. This case emphasizes the comorbidity of psychiatric involvement in MSUD, which contributes to metabolic decompensation that can lead to cerebral edema and death. This case also highlights the pressing need for enhanced strategies for the acute management and long-term care of MSUD patients with psychiatric involvement, particularly in scenarios where mental disturbance could lead to noncompliance.