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.

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

High Systemic Inflammatory Protein Index Is Associated with Clinically Ineffective Reperfusion in Acute Anterior Circulation Ischemic Stroke Patients Undergoing Endovascular Treatment.

Nearly half of the patients undergoing endovascular treatment (EVT) do not have favorable outcomes despite successful recanalization of the occluded artery, which is also known as clinically ineffective reperfusion. We proposed a novel index-the systemic inflammatory protein index (SIPI), based on albumin, globulin, and C-reaction protein (CRP). We aimed to evaluate the relationship between inflammatory biomarkers at varying time points and the 90-day functional outcomes and investigate inflammatory biomarkers' dynamic changes during hospitalization in acute ischemic stroke (AIS) patients of anterior circulation undergoing EVT. We retrospectively recruited consecutive patients diagnosed with AIS of anterior circulation and treated with EVT from January 2018 to June 2022 in Nanfang Hospital. Albumin, globulin, and CRP were recorded on admission, 1 day, 3 days, and 7 days after EVT. An unfavorable functional outcome was defined as 90-day modified Rankin Scale (mRS) of 3-6. Albumin-to-globulin ratio (AGR), C-reactive protein-to-albumin ratio (CAR), and SIPI were calculated as follows: AGR = albumin/globulin; CAR = CRP/albumin; SIPI = CRP × globulin/albumin. A total of 238 consecutive anterior circulation AIS patients with EVT were included, among which 145 (60.9%) patients had unfavorable outcomes. After adjusting for confounding factors, admission globulin, admission AGR, 1-day AGR, 3-day albumin, 3-day CRP, 3-day CAR, 3-day SIPI, 7-day albumin, 7-day CRP, 7-day CAR, and 7-day SIPI showed an independent association with 90-day functional outcome. Of them, 3-day SIPI had the most robust discriminative ability with an area under the curve of 0.719 (CI 0.630-0.808, p < 0.001). There were differences in the dynamic change of inflammatory biomarkers between the subjects with favorable and unfavorable functional outcomes. Inflammatory biomarkers, including albumin, globulin, CRP, AGR, CAR, and SIPI, are independent predictors of 90-day unfavorable outcomes in anterior circulation AIS patients with EVT. SIPI of day 3 has the highest predictive value.

Risk factors for super-refractory and mortality in generalized convulsive status epilepticus: a 10-year retrospective cohort study.

Background: Generalized convulsive status epilepticus (GCSE) is one of the most challenging life-threatening neurological emergencies. If GCSE becomes super-refractory, it is associated with significant mortality. Although aggressive management of prolonged status epilepticus was conducted, the mortality has not decreased since the late 1990s. Objectives: The present study aimed to explore the risk factors for progression to super-refractory in patients with generalized convulsive status epilepticus (GCSE). Moreover, we illustrated the risk factors for mortality in GCSE patients. Design: An observational retrospective cohort study. Methods: We conducted a retrospective study of patients with GCSE admitted to our neurocritical unit, in Guangzhou, China, from October 2010 to February 2021. The data of sociodemographic information, etiology, laboratory results, treatment, and prognosis were collected and analyzed. Results: A total of 106 patients were enrolled; 51 (48%) of them developed super-refractory status epilepticus (SRSE). Multivariate logistic regression analysis demonstrated that patients with autoimmune encephalitis (p = 0.015) and intracranial infection (p = 0.019) are likely to progress to SRSE. The in-hospital mortality was 11.8% and 9.1% for patients in the SRSE and non-SRSE groups, respectively (p = 0.652). Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratios (NLR) at admission were independently associated with in-hospital mortality. Up to 31.4% of SRSE patients and 29.1% of non-SRSE patients died within 6 months after discharge (p = 0.798). Multivariate logistic regression analysis showed that plasma exchange (PE) was a protective factor for 6-month mortality. A high NLR at discharge was a risk factor for 6-month mortality. Conclusion: In the current study, about 48% of GCSE patients progressed to SRSE. Regarding etiology, autoimmune encephalitis or intracranial infection was prone to SRSE. No significant differences were observed in the in-hospital and 6-month mortality between SRSE and non-SRSE groups. Multivariate logistic regression analysis showed that NLR at admission and discharge was an independent predictor of in-hospital and 6-month mortality, respectively. Moreover, PE significantly reduced the 6-month mortality.

Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial.

Background: Glibenclamide alleviates brain edema and improves neurological outcomes in experimental models of stroke. We aimed to assess whether glibenclamide improves functional outcomes in patients with acute ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Methods: In this randomized, double-blind, placebo-controlled trial, patients with acute ischemic stroke were recruited to eight academic hospitals in China. Patients were eligible if they were aged 18-74 years, presented with a symptomatic anterior circulation occlusion with a deficit on the NIHSS of 4-25, and had been treated with rtPA within 4.5 h of symptom onset. We used web-based randomization (1:1) to allocate eligible participants to the glibenclamide or placebo group, stratified according to endovascular treatment and baseline stroke severity. Glibenclamide or placebo was taken orally or via tube feeding at a loading dose of 1.25 mg within 10 h after symptom onset, followed by 0.625 mg every 8 h for 5 days. The primary outcome was the proportion of patients with good outcomes (modified Rankin Scale of 0-2) at 90 days, assessed in all randomly assigned patients who had been correctly diagnosed and had begun study medication. The study is registered with ClinicalTrials.gov, NCT03284463, and is closed to new participants. Findings: Between January 1, 2018, and May 28, 2022, 305 patients were randomly assigned, of whom 272 (142 received glibenclamide and 130 received placebo) were included in the primary efficacy analysis. 103 (73%) patients in the glibenclamide group and 94 (72%) in the placebo group had a good outcome (adjusted risk difference 0.002, 95% CI -0.098 to 0.103; p = 0.96). 12 (8%) patients allocated to glibenclamide and seven (5%) patients allocated to placebo died from any cause at 90 days (p = 0.35). The number and type of adverse events were similar between the two groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: The addition of glibenclamide to thrombolytic therapy did not increase the proportion of patients who achieved good outcomes after stroke compared with placebo, but it did not lead to any safety concerns. Funding: Southern Medical University and Nanfang Hospital.

A decision-making method for reservoir operation schemes based on deep learning and whale optimization algorithm.

Reservoir operation is an important part of basin water resources management. The rational use of reservoir operation scheme can not only enhance the capacity of flood control and disaster reduction in the basin, but also improve the efficiency of water use and give full play to the comprehensive role the reservoir. The conventional decision-making method of reservoir operation scheme is computationally large, subjectivity and difficult to capture the nonlinear relationship. To solve these problems, this paper proposes a reservoir operation scheme decision-making model IWGAN-IWOA-CNN based on artificial intelligence and deep learning technology. In view of the lack of data in the original reservoir operation scheme and the limited improvement of data characteristics by the traditional data augmentation algorithm, an improved generative adversarial network algorithm (IWGAN) is proposed. IWGAN uses the loss function which integrates Wasserstein distance, gradient penalty and difference item, and dynamically adds random noise in the process of model training. The whale optimization algorithm is improved by introducing Logistic chaotic mapping to initialize population, non-linear convergence factor and adaptive weights, and Levy flight perturbation strategy. The improved whale optimization algorithm (IWOA) is used to optimize hyperparameters of convolutional neural networks (CNN), so as to obtain the best parameters for model prediction. The experimental results show that the data generated by IWGAN has certain representation ability and high quality; IWOA has faster convergence speed, higher convergence accuracy and better stability; IWGAN-IWOA-CNN model has higher prediction accuracy and reliability of scheme selection.

The Performances of SNAQ, GLIM, mNICE, and ASPEN for Identification of Neurocritically Ill Patients at High Risk of Developing Refeeding Syndrome.

We previously found that neurocritically ill patients are prone to refeeding syndrome (RFS), a potentially life-threatening complication. However, there is no unified or validated consensus on the screening tool for RFS so far. We aimed to validate and compare the performance of four screening tools for RFS in neurocritically ill patients. We conducted a single-center, observational, retrospective cohort study among neurocritically ill adult patients who were admitted to the neurocritical care unit (NCU), and who received enteral nutrition for 72 h or longer. They were scored on the Short Nutritional Assessment Questionnaire (SNAQ), the Global Leadership Initiative on Malnutrition (GLIM), the modified criteria of the Britain's National Institute for Health and Care Excellence (mNICE), and ASPEN Consensus Recommendations for Refeeding Syndrome (ASPEN) scales to predict RFS risk via admission data. The performance of each scale in predicting RFS was evaluated. Logistic regression analysis was used to identify the independent risk factors for RFS, and they were added to the above scales to strengthen the identification of RFS. Of the 478 patients included, 84 (17.57%) developed RFS. The sensitivity of the SNAQ and GLIM was only 20.2% (12.6-30.7%), although they had excellent specificities of 84.8% (80.8-88.1%) and 86.0% (82.1-89.2%), respectively; mNICE predicted RFS with a sensitivity of 48.8% (37.8-59.9%) and a specificity of 65.0% (60.0-69.9%); ASPEN had the highest Youden index, with a sensitivity and specificity of 53.6% (42.4-64.4%) and 64.7% (59.8-69.4%), respectively. The Area Under the receiver operating characteristic Curves (AUC) of SNAQ, GLIM, mNICE, and ASPEN to predict RFS were 0.516 (0.470-0.561), 0.533 (0.487-0.579), 0.568 (0.522-0.613), and 0.597 (0.551-0.641), respectively. We identified age, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Glasgow Coma Scale (GCS) score as independent risk factors of RFS, and the combination of GCS and age can improve the AUC of ASPEN to 0.664 (0.620-0.706) for predicting RFS. SNAQ, GLIM, mNICE, and ASPEN do not perform well in identifying neurocritically ill patients at high risk of RFS, although ASPEN appears to have relatively a good validity among them. Combining GCS and age with ASPEN slightly improves RFS recognition, but it still leaves a lot of room for improvement.

Predicting futile recanalization, malignant cerebral edema, and cerebral herniation using intelligible ensemble machine learning following mechanical thrombectomy for acute ischemic stroke.

Purpose: To establish an ensemble machine learning (ML) model for predicting the risk of futile recanalization, malignant cerebral edema (MCE), and cerebral herniation (CH) in patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and recanalization. Methods: This prospective study included 110 patients with premorbid mRS ≤ 2 who met the inclusion criteria. Futile recanalization was defined as a 90-day modified Rankin Scale score >2. Clinical and imaging data were used to construct five ML models that were fused into a logistic regression algorithm using the stacking method (LR-Stacking). We added the Shapley Additive Explanation method to display crucial factors and explain the decision process of models for each patient. Prediction performances were compared using area under the receiver operating characteristic curve (AUC), F1-score, and decision curve analysis (DCA). Results: A total of 61 patients (55.5%) experienced futile recanalization, and 34 (30.9%) and 22 (20.0%) patients developed MCE and CH, respectively. In test set, the AUCs for the LR-Stacking model were 0.949, 0.885, and 0.904 for the three outcomes mentioned above. The F1-scores were 0.882, 0.895, and 0.909, respectively. The DCA showed that the LR-Stacking model provided more net benefits for predicting MCE and CH. The most important factors were the hypodensity volume and proportion in the corresponding vascular supply area. Conclusion: Using the ensemble ML model to analyze the clinical and imaging data of AIS patients with successful recanalization at admission and within 24 h after MT allowed for accurately predicting the risks of futile recanalization, MCE, and CH.

Flufenamic acid improves survival and neurologic outcome after successful cardiopulmonary resuscitation in mice.

BACKGROUND: Brain injury is the main cause of high mortality and disability after successful cardiopulmonary resuscitation (CPR) from sudden cardiac arrest (CA). The transient receptor potential M4 (TRPM4) channel is a novel target for ameliorating blood-brain barrier (BBB) disruption and neuroinflammation. Herein, we tested whether flufenamic acid (FFA), which is reported to block TRPM4 with high potency, could confer neuroprotection against brain injury secondary to CA/CPR and whether its action was exerted by blocking the TRPM4 channel. METHODS: Wild-type (WT) and Trpm4 knockout (Trpm4-/-) mice subjected to 10-min CA/CPR were randomized to receive FFA or vehicle once daily. Post-CA/CPR brain injuries including neurologic deficits, survival rate, histological damage, edema formation, BBB destabilization and neuroinflammation were assessed. RESULTS: In WT mice subjected to CA/CPR, FFA was effective in improving survival and neurologic outcome, reducing neuropathological injuries, attenuating brain edema, lessening the leakage of IgG and Evans blue dye, restoring tight junction protein expression and promoting microglia/macrophages from the pro-inflammatory subtype toward the anti-inflammatory subtype. In comparison to WT mice, Trpm4-/- mice exhibited less neurologic deficiency, milder histological impairment, more BBB integrity and more anti-inflammatory microglia/macrophage polarization. As expected, FFA did not provide a benefit of superposition compared with vehicle in the Trpm4-/- mice after CA/CPR. CONCLUSIONS: FFA mitigates BBB breach and modifies the functional status of microglia/macrophages, thereby improving survival and neurologic deficits following CA/CPR. The neuroprotective effects occur at least partially by interfering with the TRPM4 channel in the neurovascular unit. These results indicate the significant clinical potential of FFA to improve the prognosis for CA victims who are successfully resuscitated.

Glibenclamide Directly Prevents Neuroinflammation by Targeting SUR1-TRPM4-Mediated NLRP3 Inflammasome Activation In Microglia.

Glibenclamide (GLB) reduces brain edema and improves neurological outcome in animal experiments and preliminary clinical studies. Recent studies also suggested a strong anti-inflammatory effect of GLB, via inhibiting nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation. However, it remains unknown whether the anti-inflammatory effect of GLB is independent of its role in preventing brain edema, and how GLB inhibits the NLRP3 inflammasome is not fully understood. Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. The Trpm4 siRNA and GLB were injected to block sulfonylurea receptor 1-transient receptor potential M4 (SUR1-TRPM4) channel in rats. Western blotting, quantitative real-time polymerase chain reaction, behavioral analysis, and histological examination were used to evaluate the role of GLB in preventing NLRP3-mediated neuroinflammation through inhibiting SUR1-TRPM4, and corresponding neuroprotective effect. To further explore the underlying mechanism, BV2 cells were subjected to lipopolysaccharides, or oxygen-glucose deprivation/reperfusion. Here, in rat model of cardiac arrest with brain edema combined with neuroinflammation, GLB significantly alleviated neurocognitive deficit and neuropathological damage, via the inhibition of microglial NLRP3 inflammasome activation by blocking SUR1-TRPM4. Of note, the above effects of GLB could be achieved by knockdown of Trpm4. In vitro under circumstance of eliminating distractions from brain edema, SUR1-TRPM4 and NLRP3 inflammasome were also activated in BV2 cells subjected to lipopolysaccharides, or oxygen-glucose deprivation/reperfusion, which could be blocked by GLB or 9-phenanthrol, a TRPM4 inhibitor. Importantly, activation of SUR1-TRPM4 in BV2 cells required the P2X7 receptor-mediated Ca2+ influx, which in turn magnified the K+ efflux via the Na+ influx-driven opening of K+ channels, leading to the NLRP3 inflammasome activation. These findings suggest that GLB has a direct anti-inflammatory neuroprotective effect independent of its role in preventing brain edema, through inhibition of SUR1-TRPM4 which amplifies K+ efflux and promotes NLRP3 inflammasome activation.

Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke.

The breakdown of the blood-brain barrier (BBB) is related to the occurrence and deterioration of neurological dysfunction in ischemic stroke, which leads to the extravasation of blood-borne substances, resulting in vasogenic edema and increased mortality. However, a limited understanding of the molecular mechanisms that control the restrictive properties of the BBB hinders the manipulation of the BBB in disease and treatment. Here, we found that the glycocalyx (GCX) is a critical factor in the regulation of brain endothelial barrier integrity. First, endothelial GCX displayed a biphasic change pattern, of which the timescale matched well with the biphasic evolution of BBB permeability to tracers within the first week after t-MCAO. Moreover, GCX destruction with hyaluronidase increased BBB permeability in healthy mice and aggravated BBB leakage in transient middle cerebral artery occlusion (t-MCAO) mice. Surprisingly, ultrastructural observation showed that GCX destruction was accompanied by increased endothelial transcytosis at the ischemic BBB, while the tight junctions remained morphologically and functionally intact. Knockdown of caveolin1 (Cav1) suppressed endothelial transcytosis, leading to reduced BBB permeability, and brain edema. Lastly, a coimmunoprecipitation assay showed that GCX degradation enhanced the interaction between syndecan1 and Src by promoting the binding of phosphorylated syndecan1 to the Src SH2 domain, which led to rapid modulation of cytoskeletal proteins to promote caveolae-mediated endocytosis. Overall, these findings demonstrate that the dynamic degradation and reconstruction of GCX may account for the biphasic changes in BBB permeability in ischemic stroke, and reveal an essential role of GCX in suppressing transcellular transport in brain endothelial cells to maintain BBB integrity. Targeting GCX may provide a novel strategy for managing BBB dysfunction and central nervous system drug delivery.

Impact of early protein provision on the mortality of acute critically ill stroke patients.

BACKGROUND: Stroke is the leading cause of death in China, and dysphagia is a common symptom of stroke. For acute critically ill stroke patients, whether the protein provision overwhelming calorie provision impacts the outcome still requires investigation. MATERIALS AND METHODS: We conducted a retrospectively observational study. Acute stroke patients admitted to our neurocritical care unit between January 2013 and January 2017 were enrolled. Primary end points were short-term (30-day) and long-term (6-month) mortality, as well as long-term poor outcome with a modified Rankin scale score ≥4. RESULTS: Of 208 eligible patients, 127 (61.1%) patients were diagnosed with acute ischemic stroke and 81 (38.9%) with intracranial hemorrhage. In multivariate logistic regression analysis, the increased protein provision was significantly associated with reduced 30-day and 6-month mortality (P = .041 and P = .020, respectively) but not 6-month functional outcome (P = .365), whereas calorie provision had no independent association with either mortality or functional outcome. When the protein provision ≤1.74 g/kg/day, there was a 9.37% decrease in short-term mortality and a 9.21% decrease in long-term mortality with each 0.1 g/kg/day increase in protein delivery. The patients were further divided into five subgroups based on the amount of protein provision, and Linear-by-Linear Association tests showed there was a negative linear relationship between the protein provision and 30-day and 6-month mortality (P = .048 and P = .017, respectively). CONCLUSIONS: Early protein provision during the first week is an independent predictor of short-term and long-term mortality in acute critically ill stroke patients.

Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus.

Status epilepticus (SE) is a neurological emergency usually accompanied by acute cerebral edema and long-term cognitive impairment, and is characterized by neurodegeneration and aberrant hyperphosphorylated tau protein (p-tau) aggregation. The glia-lymphatic (glymphatic) system plays a central role in facilitating the clearance of metabolic waste from the brain, but its relationship with cerebral edema and cognitive dysfunction after SE is unclear. We hypothesized that cerebral edema after SE might impair glymphatic system function through compression, thus leading to impaired removal of metabolic waste, and ultimately affecting long-term cognitive function. Our results showed that glymphatic system function was temporarily impaired, as evidenced by 2-photon imaging, MRI enhancement, imaging of brain sections, and astrocytic water channel aquaporin 4 (AQP4) protein polarization. The severity of cerebral edema on MRI correlated well with glymphatic system dysfunction within 8 days following SE. Moreover, when cerebral edema was alleviated by glibenclamide treatment or genetic deletion of Trpm4, post-SE glymphatic system function recovered earlier, along with fewer p-tau-deposited neurons and neuronal degeneration and better cognitive function. These findings suggest that SE-induced cerebral edema may cause glymphatic system dysfunction and render the post-SE brain vulnerable to p-tau aggregation and neurocognitive impairment.

Incidence and outcome of refeeding syndrome in neurocritically ill patients.

BACKGROUND & AIM: Neurocritically ill patients are more likely to be comatose and suffer from dysphagia, conditions that inevitably require nutritional support. Inappropriate nutritional support may lead to refeeding syndrome (RFS). This study aimed to explore the incidence and outcome of RFS in neurocritically ill patients. METHODS: We conducted a retrospective study among neurocritically ill patients who received total enteral nutrition for >72 h in a university-affiliated hospital. RFS was defined as the occurrence of new-onset hypophosphatemia (<0.65 mmol/L) within 72 h of the commencement of nutritional support. The primary outcome was 6-month mortality. The secondary outcomes included 30-day mortality, neurocritical care unit (NCU) stay, and hospital length of stay. RESULTS: A total of 328 patients were enrolled, and 56 (17.1%) of them developed RFS within 72 h of nutrition support. Significantly, we found that patients with high malnutrition universal screening tool (MUST) and sequential organ failure assessment (SOFA) scores were more likely to develop RFS. The occurrence of RFS was associated with a longer NCU stay, higher 30-day mortality and 6-month mortality, and poorer 6-month functional outcome. Moreover, RFS was identified as an independent risk factor for 6-month mortality. CONCLUSION: RFS is not rare in neurocritically ill patients and is more likely to occur in patients with nutritional risk and more severe conditions. RFS is an independent risk factor for 6-month mortality in neurocritically ill patients.

Cerebral autoregulation is heterogeneous in different stroke mechanism of ischemic stroke caused by intracranial atherosclerotic stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is the most common cause of ischemic stroke (IS) and is associated with stroke recurrence. It results in IS due to a variety of mechanisms. However, the influence of brain reserve mechanism on different stroke mechanism is still unclear. Cerebral autoregulation (CA) is an important brain reserve mechanism and is impaired after IS. This study aimed to explore the impaired pattern of CA and assess the association between CA and stroke risk factors in different stroke mechanism caused by ICAS. METHODS: IS patients with ICAS (50%-99% stenosis/occlusion) in middle cerebral artery (MCA) or internal carotid artery were enrolled to receive CA examinations within 7 days after onset. Healthy volunteers were also recruited as controls. CA was recorded from spontaneous fluctuations of blood pressure and MCA flow velocity. Transfer function analysis was used to derive CA parameters, including phase difference (PD) and coherence in the low-frequency range (0.06-0.12 Hz). RESULTS: A total of 89 IS patients and 90 healthy controls were included. Compared with controls, CA was impaired ipsilaterally in patients with parent artery atherosclerosis occluding penetrating artery (POPA) while CA was bilaterally impaired in other stroke mechanisms. And CA on ipsilateral hemisphere was correlated with hypertension/hyperlipidemia in patients with POPA (r = -0.481, p = .008; r = -0.484, p = .008). While CA on ipsilateral hemisphere was correlated with perfusion parameter including the arterial spin-labeling (ASL) parameter cerebral blood flow (CBF) (r = 0.893, p = .007) and collateral circulation status the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) (r = 0.610, p = .021) in patients with hypoperfusion mechanism. CONCLUSION: In IS patients, CA was impaired heterogeneously and was correlated with different risk factors in varied stroke mechanism. CA can be as an informative determinant of stroke risk in patients with ICAS and to help improving individualized treatment strategies in the presence of ischemic stroke caused by ICAS.

Knockout of Transient Receptor Potential Melastatin 4 Channel Mitigates Cerebral Edema and Neuronal Injury After Status Epilepticus in Mice.

This study aimed to evaluate whether the knockout of transient receptor potential melastatin 4 (TRPM4) could reduce cerebral edema and improve neurologic outcome in a mouse model of status epilepticus (SE). Wild-type (WT) (n = 61) and Trpm4-/- mice (n = 61) with behavioral seizures induced by lithium (10 mEq/kg) and pilocarpine (30-40 mg/kg) were terminated 2.5 hours after the onset of SE. After SE, 28 WT-SE and 27 Trpm4-/--SE mice were observed for 28 days and assessed for survival and cognitive function; the others were killed after 24 hours, 72 hours, or 7 days, and evaluated for cerebral edema and histological injury. In comparison to WT-SE mice, the mortality and cognitive deficit for Trpm4-/--SE mice following SE after 28 days were significantly ameliorated. Trpm4-/--SE mice also showed less water content and cerebral edema assessed by magnetic resonance imaging, and decreased blood-brain barrier breakdown after SE. Moreover, Trpm4 deficiency significantly mitigated neuronal loss, cellular necrosis and apoptosis in the hippocampus and piriform cortex and mitigated astrocytosis and microgliosis. In conclusion, this study suggests that Trmp4 may represent a new target for improving outcomes after SE.

Publisher Correction: Reservoir characteristics and logging evaluation of gas - bearing mudstone in the south of North China Plain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biomarkers of Unfavorable Outcome in Acute Ischemic Stroke Patients with Successful Recanalization by Endovascular Thrombectomy.

BACKGROUND: We aimed to identify plasma markers of unfavorable outcomes for patients with acute ischemic stroke (AIS) after recanalization by endovascular thrombectomy (EVT). METHODS: From November 2017 to May 2019, we prospectively collected 61 AIS patients due to anterior large vessel occlusion who achieved recanalization by EVT. Plasma samples were obtained between 18 and 24 h after recanalization. Unfavorable outcomes included futile recanalization at 90 days and overall early complications within 7 days after EVT. RESULTS: After adjustment for age and initial National Institute of Health Stroke Scale (NIHSS), matrix metalloproteinase-9 (MMP-9), tenascin-C, thioredoxin, ADAMTS13, and gelsolin were independently associated with both futile recanalization and overall early complications significantly (all p < 0.05), while C-reactive protein (CRP) was independently associated with overall early complications (p = 0.031) but at the limit of significance for futile recanalization (p = 0.051). The baseline clinical model (BCM) (including age and initial NIHSS) demonstrated discriminating ability to indicate futile recanalization (area under the curve [AUC] 0.807, 95% confidence interval [CI] 0.693-0.921) and overall early complications (AUC 0.749, 95% CI 0.611-0.887). BCM+MMP-9+thioredoxin enhanced discrimination (AUC 0.908, 95% CI 0.839-0.978, p = 0.043) and reclassification (net reclassification improvement [NRI] 67.2%, p < 0.001) to indicate futile recanalization. With respect to overall early complications, BCM+MMP-9+tenascin-C, BCM+MMP-9+CRP, BCM+MMP-9+ADAMTS13, BCM+tenascin-C+ADAMTS13, and BCM+CRP+ADAMTS13, all improved discrimination (AUC [95% CI]: 0.868 [0.766-0.970], 0.882 [0.773-0.990], 0.886 [0.788-0.984], 0.880 [0.783-0.977], and 0.863 [0.764-0.962], respectively, all p < 0.05 by the DeLong method) and reclassification (NRI 59.1%, 71.8%, 51.1%, 67.4%, and 38.3%, respectively, all p < 0.05). CONCLUSIONS: The increased levels of MMP-9, tenascin-C, CRP, thioredoxin, and decreased levels of ADAMTS13 and gelsolin were independent predictors of futile recanalization in AIS patients after recanalization by EVT.

Glutamic acid decarboxylase antibodies in neurocritical patients: a culprit or a bystander?

BACKGROUND: Glutamic acid decarboxylase (GAD) is an intracellular enzyme, which is widely expressed in central nervous system (CNS), pancreas, and other organs. GAD antibodies (GAD-Abs) are linked to various neurological disorders. However, the significance of GAD-Abs in neurocritical patients is undetermined. MATERIALS AND METHODS: Patients with serologically positive GAD-Abs and requiring neurocritical care were included. The clinical, laboratory, and outcome data were retrospectively collected. RESULTS: We included 9 patients with serologically positive GAD-Abs. Clinical manifestations involved both CNS and peripheral nervous system (PNS). Six (66.7%) patients had other specific autoimmune antibodies. Non-specific autoimmune responses were observed in 8 (88.9%) patients. All patients clinically responded well to immunotherapy. The titers of GAD-Abs decreased in 7 (77.8%) patients but remained unchanged in the other 2 patients. One (11.1%) patient awoke before the negative conversion of GAD-Abs, and 3 (33.3%) patients remained unconscious and/or under mechanical ventilation for several weeks after the vanishing of GAD-Abs. CONCLUSIONS: Most neurocritical patients with serologically positive GAD-Abs had other specific autoimmune antibodies. All patients responded well to immunotherapy, but not parallel to the titers of GAD-Abs. These results indicated that GAD-Abs might be more a bystander than a culprit in neurocritical patients, suggesting that an underlying autoimmune disease should be explored.