Delayed Encephalopathy After Acute Carbon Monoxide Poisoning Research Articles

Sodium butyrate exerts a neuroprotective effect in rats with acute carbon monoxide poisoning by activating autophagy through the mTOR signaling pathway

Acute carbon monoxide (CO) poisoning is a prevalent type of poisoning that causes significant harm globally. Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a severe complication that occurs after acute CO poisoning; however, the exact underlying pathological cause of DEACMP remains unclear. Accumulating evidence indicates that abnormal inflammation and immune-mediated brain damage, cellular apoptosis and autophagy, and direct neuronal toxicity are involved in the development of delayed neurologic sequelae. Sodium butyrate, a histone deacetylase inhibitor, has gained increasing attention for its numerous beneficial effects on various diseases, such as obesity, diabetes, inflammatory diseases, and cerebral damage. In this study, an acute carbon monoxide poisoning (ACOP) model is established in rats to investigate the mechanism of CO poisoning and the therapeutic potential of sodium butyrate. The results suggested that the ACOP rats had impaired spatial memory, and cell apoptosis was observed in the hippocampi with activated autophagy. Sodium butyrate treatment further increased the activation of autophagy in the hippocampi of CO-exposed rats, inhibited apoptosis, and consolidated spatial memory. These findings indicated that sodium butyrate may improve memory and cognitive function in ACMP rats by promoting autophagy and inhibiting apoptosis.

Effect of hyperbaric oxygen on symptoms of dementia in patients with delayed encephalopathy after acute carbon monoxide poisoning.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most severe complication of carbon monoxide poisoning, which seriously endangers patients' quality of life. This study aims to investigate the efficacy of hyperbaric oxygen (HBO2) on improving dementia symptoms in patients with DEACMP. A retrospective analysis was performed on DEACMP patients, who visited Xiangya Hospital, Central South University from June 2014 to June 2020. Among them, patients who received conventional drug treatment combined with HBO2 treatment were included in an HBO2 group, while those who only received conventional drug treatment were included in a control group. HBO2 was administered once daily. Patients in the HBO2 group received 6 courses of treatment, with each course consisting of 10 sessions. The Hasegawa Dementia Scale (HDS) was used to diagnose dementia, and the Clinical Dementia Rating (CDR) was used to grade the severity of dementia for DEACMP. The Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-Cog), the Functional Activities Questionnaire (FAQ), the Neuropsychiatric Inventory (NPI), and the Clinician's Interview-Based Impression of Change-Plus Caregiver Input (CIBIC-Plus) were performed to assess cognitive function, ability to perform activities of daily living (ADL), behavioral and psychological symptoms, and overall function. The study further analyzed the results of objective examinations related to patients' dementia symptoms, including magnetic resonance imaging detection of white matter lesions and abnormal electroencephalogram (EEG). The changes of the above indicators before and after treatment, as well as the differences between the 2 groups after treatment were compared. There was no significant difference in the HDS score and CDR grading between the 2 groups before treatment (both P>0.05). After treatment, the score of ADAS-Cog, FAQ, NPI, and CIBIC Plus grading of the 2 groups were significantly improved, and the improvement of the above indicators in the HBO2 group was greater than that in the control group (all P<0.05). The effective rate of the HBO2 group in treating DEACMP was significantly higher than that of the control group (89.47% vs 65.87%, P<0.05). The objective examination results (white matter lesions and abnormal EEG) showed that the recovery of patients in the HBO2 group was better than that in the control group. Hyperbaric oxygen can significantly relieve the symptoms of dementia in patients with DEACMP.

Development of a Nomogram Based on Diffusion-Weighted Imaging and Clinical Information to Predict Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a severe complication that can arise from acute carbon monoxide poisoning (ACOP). This study aims to identify the independent risk factors associated with DEACMP and to develop a nomogram to predict the probability of developing DEACMP. The data of patients diagnosed with ACOP between September 2015 and June 2021 were analyzed retrospectively. The patients were divided into the two groups: the DEACMP group and the non-DEACMP group. Univariate analysis and multivariate logistic regression analysis were conducted to identify the independent risk factors for DEACMP. Subsequently, a nomogram was constructed to predict the probability of DEACMP. The study included 122 patients, out of whom 30 (24.6%) developed DEACMP. The multivariate logistic regression analysis revealed that acute high-signal lesions on diffusion-weighted imaging (DWI), duration of carbon monoxide (CO) exposure, and Glasgow Coma Scale (GCS) score were independent risk factors for DEACMP (Odds Ratio = 6.230, 1.323, 0.714, p < 0.05). Based on these indicators, a predictive nomogram was constructed. This study constructed a nomogram for predicting DEACMP using high-signal lesions on DWI and clinical indicators. The nomogram may serve as a dependable tool to differentiate high-risk patients and enable the provision of personalized treatment to lower the incidence of DEACMP.

LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the most common complications following carbon monoxide intoxication. Long noncoding RNAs (lncRNAs) exert critical functions in numerous neurological disorders. We intended to investigate the role of CRNDE in DEACMP. The DEACMP model in rats and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in PC-12 cells were established. Brain and cell injuries were assessed with H&E staining, Nissl staining, TUNEL and CCK8 assays, respectively. Related proteins and RNAs were quantified with western blot and qRT-PCR. The N6-methyladenosine (m6A) level was determined using MeRIP-qPCR and immunofluorescence. Loss and gain function studies were performed to investigate the biological function of CRNDE. The potential mechanisms between each factor were explored using RNA immunoprecipitation, RNA-pull down and co-immunoprecipitation. CRNDE was increased in the hippocampal tissues of DEACMP rats and in OGD/R-treated PC-12 cells, which was positively correlated to m6A modification. Knockdown of CRNDE reduced cell damage and elevated UCHL5 and SMO expressions in OGD/R-treated PC-12 cells. hnRNPA1 was upregulated in DEACMP. In addition, inhibiting hnRNPA1 prevented apoptosis in PC-12 cells subjected to OGD/R. hnRNPA1 bound to CRNDE and remained in the nucleus, which inhibited UCHL5 expression through the formation of CRNDE-hnRNPA1-mRNA complex. UCHL5 could inhibit SMO ubiquitination and suppress PC-12 cell apoptosis during OGD/R. CRNDE silencing blocked brain injury in DEACMP, while knocking down UCHL5 reversed these effects. CRNDE interacted with hnRNPA1 to facilitate DEACMP via inhibition of UCHL5-mediated SMO deubiquitination. CRNDE might be a latent therapeutic target for treating DEACMP.

Investigation of the relationship between MBP gene polymorphisms and delayed encephalopathy after acute carbon monoxide poisoning

Increasing evidence reveals that delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) results from the combined effects of environmental and genetic factors. The main pathological feature of DEACMP was generalized demyelination of cerebral white matter. Myelin basic protein (MBP) levels in cerebrospinal fluid (CSF) and serum samples from DEACMP patients were elevated. This study investigated the association of MBP single nucleotide polymorphisms(SNPs) (rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336) with DEACMP. We genotyped 416 DEACMP patients and 785 age, educational level, and sex-matched ACMP patients for rs470555, rs470724, rs4890785, rs595997, rs76452994, and rs921336 SNPs using the Agena MassArray. There were no significant differences in the allele frequency distribution, four genetic models, and genotype distributions between the DEACMP and ACMP groups for rs470555, rs470724, rs4890785, and rs595997. However, significant differences were observed for rs76452994 and rs921336. This study revealed that the MBP polymorphisms, rs470555, rs470724, rs4890785, and rs595997, were not associated with DEACMP. Based on the codominant, dominant, and overdominant genetic inheritability patterns, the MBP rs76452994 and rs921366 polymorphisms were associated with DEACMP. Furthermore, the G allele of rs76452994 and T allele of rs921336 could lead to higher DEACMP risk.

Prognostic factors of hyperbaric oxygen therapy for patients with delayed encephalopathy after acute carbon monoxide poisoning

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a disease with an incomplete pathological mechanism, long treatment time, and uncertain factors affecting the therapeutic effect. This study explored prognostic factors for DEACMP patients treated with hyperbaric oxygen therapy (HBOT) in 15 hospitals in China. The findings might provide a theoretical basis for further improving the prognosis of DEACMP patients.In this study, data from 330 patients with DEACMP who were admitted to HBOT centers of 15 hospitals in Hunan Province (China) from June 2015 to June 2020 were retrospectively analyzed, and their medical records related to disease prognosis were collected and followed up by telephone. Univariate and multivariate analyses were used to identify independent risk factors for the prognosis of DEACMP patients after HBOT. Univariate analysis revealed 11 possible prognostic factors. Consistent with univariate analysis, multivariate analysis found that underlying diseases (Odds radio(OR) = 2.886, P = 0.048), hypermyotonia (OR = 5.2558, P = 0.008), and HBOT pressure no less Than 2.3 atm absolute (ATA) ((OR = 7.812, P = 0.004) were identified as independent prognostic factors among 20 variables for poor prognosis of DEACMP patients treated with HBOT in the study. This multicenter retrospective analysis revealed that the adverse prognostic markers for DEACMP patients treated with HBOT might be underlying diseases, hypermyotonia, and an HBOT pressure of 2.3 ATA or higher.

Early predictors of brain injury in patients with acute carbon monoxide poisoning and the neuroprotection of mild hypothermia

IntroductionCarbon monoxide (CO) poisoning can cause serious neurological sequelae. However, there is neither effective treatment strategy nor reliable indicators to determine the prognosis of patients with CO poisoning. The present study aimed to observe the changes of neurological function score, disease severity score, cerebral oxygen utilization (O2UCc), bispectral (BIS) index and neuron-specific enolase (NSE) concentration, and to elucidate the clinical significance of these potential indicators and the neuroprotective effect of mild hypothermia on brain injury in patients with severe acute CO poisoning. Materials and methodsA total of 277 patients with acute severe CO poisoning from 2013 to 2018 were enrolled in our hospital. Patients were divided into three groups according to their body temperature on the day of admission and their willingness to treat: a fever group (n = 78), a normal temperature group (NT group, n = 113), and a mild hypothermia group (MH group, n = 86). All patients were given hyperbaric oxygen therapy, while those in the MH group received additional mild hypothermia treatment. The severity of the disease, the neurobehavioral status, the incidence of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), and other indicators including BIS, O2UCc, NSE were further evaluated in all patients at given time-points. ResultsMild hypothermia therapy improved the prognosis of patients with CO poisoning, significantly decreased the value of O2UCc and NSE, and up-regulated BIS. The incidence of DEACMP at 6 months was 27% in the fever group, 23% in the NT group, and 8% in the MH group. The values of Glasgow-Pittsburgh coma scale (G-P score), BIS index and NSE were closely related to the occurrence of DEACMP, the cutoff values were 12.41, 52.17 and 35.20 ng/mL, and the sensitivity and specificity were 79.3%, 77.6%, 79.3% and 67.6%, 89.5%, 88.6% in the receiver operating characteristic curve (ROC), respectively. ConclusionsEarly mild hypothermia treatment could significantly reduce the severity of brain injury after CO poisoning, and might be further popularized in clinic. G-P scores, NSE and BIS index can be regarded as the prediction indicators in the occurrence and development of DEACMP. Clinical trial registrationThe study protocol was granted from Qingdao University Research Ethics Committee (Clinical trial registry and ethical approval number: QD81571283).

LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3β/β-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3β/β-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3β/β-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.

The Relationship between Cadherin Polymorphisms and the Risk of Delayed Encephalopathy after Acute Carbon Monoxide Poisoning in the Chinese Han Population.

Objective The purpose of this study was to analyze the relationship between cadherin gene single-nucleotide polymorphisms (SNPs) and the risk of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Materials and Methods A total of 416 patients with DEACMP and 754 patients with acute carbon monoxide poisoning (ACMP) were recruited. We used the Sequenom MassARRAY® system to detect cadherin gene SNPs related to DEACMP. Using different genetic analysis models, we evaluated the relationship between the cadherin gene polymorphisms and risk of DEACMP. Results We found that rs1944294 in the N-cadherin (CDH2) gene showed significant differences in genotype frequencies between the two groups under codominant and dominant inheritance models. Similarly, rs2513796 in the cadherin-17 (CDH17) gene showed significant differences under the codominant, dominant, and overdominant genetic models. And the T allele frequency of rs1944294 in the DEACMP group was significantly higher than that in the ACMP group (P = 0.023). Conclusions Cadherin gene SNPs (rs1944294, rs2513796) are associated with an increased risk of DEACMP in the Chinese population.

Inhibition of ROCK2 kinase activity improved behavioral deficits and reduced neuron damage in a DEACMP rat model

The main pathological changes that occur in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are extensive demyelination of brain white matter and neuron damage. Previous studies suggested that demyelination and neuron injury are related to activating the Rho/ROCK signaling pathway. Inhibition of the Rho/ROCK signaling pathway can alleviate neuron injury and promote myelin repair. This study utilized a DEACMP model in which rats were prepared by space injection of CO gas intraperitoneally (CO group), and the association between the Rho/ROCK signaling pathway and DEACMP was investigated. The ROCK2 kinase inhibitor Y-27632 was used to prevent the effects of the DEACMP model to elucidate its protective mechanism. The results demonstrated that the cognitive and motor functions were significantly impaired, and the GFAP, NSE, RhoA, and ROCK2 protein levels were significantly increased in the CO group within three weeks after the model was established. After Y-27632 intervention, the cognitive and motor functions of the CO+Y-27632 group were significantly improved within three weeks after the model was established. In the CO+Y-27632 group, the RhoA, ROCK2, GFAP, and NSE (indicating neuron injury) protein levels decreased significantly, and the MBP protein levels (indicating myelin repair) increased significantly within three weeks after the model was established. These results suggested that the pathogenesis of DEACMP was associated with activation of the Rho/ROCK pathway and that Y-27632 inhibited ROCK2 kinase activity in the CO exposed rats, resulting in improved behavioral deficits, reduced neuron damage, and promotion of myelin repair. Therefore, Y-27632 might be a potentially effective drug for the treatment of DEACMP-induced brain damage.

The predictive value of low T3 syndrome for delayed encephalopathy caused by severe acute carbon monoxide poisoning

Objective: To explore the predictive value of low T3 syndrome (LT3S) for patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) . Methods: In May 2020, 137 severe acute carben monoxide poisoning (SACMP) patients were selected from Harrison International Peace Hospital Affiliated to Hebei Medical University from January 2019 to January 2020 as subjects. Blood samples were taken after admission to test thyroid function. Followed up for 60 d, the patients were divided into DEACMP group (45 cases) and non DEACMP group (92 cases) according to their prognosis. Clinical data of patients in two groups were collected and compared. The Cox regression with multiple independent variables was used to analyze the independent risk factors of DEACMP. Pearson correlation analysis was used to evaluate the correlation between totall triiodochyronine (TT3) level and Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score. The receiver operating characteristic (ROC) curve of TT3 and APACHE Ⅱ scores for predicting DEACMP were drawn. Results: Compared with non DEACMP group, the age, APACHE II score, LT3S rate and diabetes prevalence in DEACMP group were higher, and the Glasgow coma scale (GCS) score was lower (P<0.05) . Cox regression analysis showed that age, APACHEⅡ score and LT3S were independent risk factors of DEACMP in patients with SACMP (OR=1.040, 95%CI:1.005-1.077; OR=1.070, 95%CI: 1.002-1.143; OR=4.210, 95%CI: 1.707-10.379; P<0.05) . Pearson correlation analysis showed that TT3 level was negatively correlated with APACHE Ⅱ score (r=-0.397, P=0.000) . ROC curve showed that the cut-off value of TT3 level for DEACMP prediction was 1.078 nmol/L, the area under curve (AUC) was 0.755, the sensitivity was 82.6%, and the specificity was 73.3%. The cut-off value of the APACHE Ⅱ score for predicting DEACMP was 16, and the AUC was 0.725, sensitivity was 93.3%, and specificity was 60.9%. Conclusion: This study showed that LT3S minght be an independent predictor of DEACMP in patients with SACMP. Thyroid function is closely related to the severity of SACMP patients.

P2Y12 receptor-mediated microglia activation involved in delayed encephalopathy after acute carbon monoxide poisoning.

To investigate the role of P2Y12 receptor-mediated microglia activation in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), we used static inhalation carbon monoxide to build DEACMP rat model. DEACMP rats were randomly assigned into DEACMP group and intervention group. A control goup was also set. The rats in intervention group received intraperitoneal injection of 100uM suramin (a P2Y12 receptor antagonist). In control group, the escape latency, level of microglia activation and ATP content were similar between different time points. In both DEACMP group and intervention group, the escape latency, level of microglia activation and ATP content were significanlty increased at 21th and 28th day. The hippocampal cells in DEACMP group and intervention group were severely and moderately, respectively, damaged at 21th and 28th day. Meanwhile, compared to control group, both DEACMP group and intervention group had significanlty longer escape latency, higher level of microglia activation and ATP content at 21th and 28th day. Compared to DEACMP group, the intervention group had significantly shorter escape latency and lower level of microglia activation at 21th and 28th day. These results suggested that the microglia activation regulated by ATP through P2Y12 receptor pathway might be closely related to the development of DEACMP.

Association between Neuron-Specific Enolase Gene Polymorphism and Delayed Encephalopathy after Acute Carbon Monoxide Poisoning.

Objective The aim of this study is to explore the relationship between neuron-specific enolase (NSE) gene polymorphism and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) and provide a theoretical basis for DEACMP pathogenesis, diagnosis, and prognosis. Methods To investigate this relationship, we screened 6 NSE single nucleotide polymorphisms (SNPs), based on the results of the previous genome-wide association studies (GWAS). A total of 1,201 patients, including 416 in the DEACMP group and 785 in the acute carbon monoxide poisoning (ACMP) group, were detected by the Sequenom MassARRAY® method. The genotype frequencies and alleles of the 6 NSE SNPs (rs2071074, rs2071417, rs2071419, rs11064464, rs11064465, and rs3213434) were compared using different genetic models. Results In the SNPs rs2071419 and rs3213434, we found that the genotypes and allele frequencies in the two groups significantly correlated with the grouping of patients (χ2 = 6.596, p = 0.037; χ2 = 8.769, p = 0.012). The haplotypes GGTTTC and CCTTTC of ACMP and DEACMP were different (χ2 = 6.563, p = 0.010; χ2 = 4.151, p = 0.042). We also observed that rs2071419 and rs3213434 significantly correlated with DEACMP-increased risk in the dominant, codominant, and overdominant genetic models. In addition, we speculated that the C allele of the rs2071419 polymorphism and the T allele of the rs3213434 polymorphism in NSE may increase the DEACMP risk (p = 0.011, p = 0.006). Conclusions The results show that rs2071419 and rs3213434 are susceptible sites of DEACMP. The NSE C allele of rs2071419 and T allele of rs3213434 and the haplotypes GGTTTC and CCTTTC may be risk factors for DEACMP.

The association study of WWP2 gene polymorphisms with delayed encephalopathy after acute carbon monoxide poisoning

Objective: To investigate the association of WWP2 single nucleotide polymorphism (rs3790088, rs4247109) with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) , and explore the influences of DEACMP genetic predisposition. Methods: From November 2006 to December 2017, 235 DEACMP cases and 429 acute carbon monoxide poisoning (ACMP) cases were selected. All ACMP patients were followed up for more than 90 days without DEACMP. The DNA in all blood samples were extracted with the blood Genome DNA Extraction Kit. The method of Sequenom Mass Array SNP technique was used to detect the genotype and allele of WWP2. All DEACMP patients were assessed every 3 days after hospitalization by the Hasegawa Dementia Scale (HDS) and Activity of Daily Living Scale (ADL) . The distribution of genotypes in conformty with Hardy-Weinderg law was analyzed by goodness-of-fit χ(2) test, and χ(2) test was used for association analysis. Results: For rs3790088, there were 226 DEACMP cases and 414 ACMP cases. For rs4247109, there were 234 DEACMP cases and 428 ACMP cases. For rs3790088 and rs4247109 in WWP2 gene: there were not significant differences in the gene genotype distribution and allele frequency of both DEACMP group and ACMP group (P>0.05) . According to gender, there were not significant differences in WWP2 gene genotype distribution and allele frequency between two female groups and two male groups (P>0.05) . After analysis by genetic model, the genotype distributions in both DEACMP group and ACMP group were not significantly differences in three genetic models (codominant genetic model, recessive genetic model and dominant genetic model, P>0.05) . Conclusion: It has not confirmed the genetic correlation between the two gene single nucleotide polymorphisms (rs3790088, rs4247109) of WWP2 gene and the incidence of DEACMP.

Altered regional homogeneity in delayed encephalopathy after carbon monoxide poisoning: A resting-state fMRI study

ObjectiveTo investigate alternations in spontaneous brain activities reflected by regional homogeneity (ReHo) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) using resting-state functional magnetic resonance imaging (rs-fMRI). MethodsTwenty-one patients with DEACMP and 21 age, sex and education matched healthy controls (HCs) received rs-fMRI scanning and clinical assessment. We used the ReHo method to analyze the interregional synchronized activity of all participants. Two sample t-tests were performed to compare the ReHo maps between the two groups. Pearson correlation analysis was then used to assess the correlations between clinical measures and abnormal ReHo in DEACMP patients. ResultsCompared with HCs, DEACMP patients showed significantly decreased ReHo in bilateral cerebellum posterior lobe, pons, bilateral basal ganglia, while increased in the posterior cingulate, calcarine, bilateral occipital lobe(GRF correction, voxel P value <0.001, cluster P value <0.05). Negative correlation was found between Mini-mental State Examination (MMSE) scores and the ReHo values of posterior cingulate gyrus (r = −0.672, p < 0.05) in the DEACMP group, while positively related to the time from CO poisoning to MRI scan (r = 0.428, p < 0.05). ConclusionPatients with DEACMP exhibited altered ReHo in the multiple functional brain regions, which provide evidence for local brain dysfunctions and may help to understand the neuropathologic mechanism for the disease.

The Efficacy of N-Butylphthalide and Dexamethasone Combined with Hyperbaric Oxygen on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

BackgroundCarbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP.Patients and MethodsA total of 171 patients with DEACMP were recruited and assigned to the combined therapy group (receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy). Conventional treatments were provided for all patients. The cognition and movement changes in patients were evaluated by the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) before and after the treatment at 1 month, 3 months, and 1 year, respectively.ResultsAt 1 month, 3 months, and 1 year after the treatment, the MMSE, MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group. There were no significant alterations in blood glucose, blood lipids, or liver and kidney function during the whole treatment session. Some patients experienced loss of appetite, mild headache and minor skin irritations. However, these patients recovered by themselves and needed no additional medications or special treatment.ConclusionThese results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the cognitive and motor functions of patients and is very safe.

Wallerian degeneration of bilateral cerebral peduncles after acute carbon monoxide poisoning

BackgroundCases of Wallerian degeneration of bilateral cerebral peduncles after acute carbon monoxide poisoning have not yet been reported. To date, most of the delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) lesions captured in magnetic resonance imaging (MRI) has been located in the subcortical white matter and basal ganglia. Here we report two cases of DEACMP with abnormalities in the bilateral cerebral peduncles. The etiology of abnormalities, which were strictly confined to the bilateral cerebral peduncles, was Wallerian degeneration secondary to upstream nerve axonal damage, making this the first report on such bilateral cerebral peduncle abnormalities after DEACMP.Case presentationIn this report, we present two cases of DEACMP with abnormal signals in the bilateral cerebral peduncles captured during brain MRIs. Case 1 was of a 68-year-old man who presented with paroxysmal disturbance of the consciousness, left limb weakness for 16 days, and lagging responses for 2 days. Case 2 was of a 55-year-old man who was unconscious for 6 h. In addition to the above mentioned characteristics on the brain MRIs, the electroencephalography of case 1 indicated that his forehead scans had a mixture of wide sharp, sharp, and three-phase waves. Brain diffusion tensor imaging of case 2 further proved that the bilateral cerebral anomalies represented Wallerian degeneration secondary to upstream axonal damage. After the definitive diagnosis, the patients returned to the local hospital for hyperbaric oxygen therapy.ConclusionsWallerian degeneration of the bilateral cerebral peduncles after acute carbon monoxide poisoning has never been reported before. The abnormal signals in the bilateral cerebral peduncles captured during brain MRIs indicated Wallerian degeneration secondary to upstream axonal damage; thus, these two cases may further our understanding of DEACMP imaging.

Imaging Prediction of the Prognosis in Carbon Monoxide Poisoning Encephalopathy: Magnetic Resonance Imaging Study

In order to explore the evaluation value of diffusion kurtosis imaging (DKI) on the prognosis of patients with carbon monoxide toxic encephalopathy, we analyzing the characteristics of early MRI and DKI images of patients with carbon monoxide poisoning encephalopathy. 19 patients with clinically confirmed acute carbon monoxide poisoning encephalopathy (5.2±1.25 days after poisoning) and 10 age-matched normal volunteers underwent routine MRI scan, of which 5 patients received DKI and MRI scan 3 weeks to 3 months after poisoning. The DKI parameters included fractionalapatipy (FA), mean diffusion (MD) and mean kurtosis (MK) were analyzed in different brain area between the case group and the normal control group. During the acute phase of carbon monoxide poisoning, MRI scans showed abnormal signal in bilateral frontal and temporal lobe cortex, subcortical white matter area and hippocampus, while bilateral cerebral white matter region and globus pallidus were showed in the patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Two of the five patients were diagnosed with DECAMP, their early MK value was increased, while the early FA value of each lesion was decreased and MD value was increased in the globus pallidus during follow-up. The change of MK value might be correlated with the prognosis of lesions. Abnormal increase of MK value in early lesions may indicate poor prognosis.

Mechanism of delayed encephalopathy after acute carbon monoxide poisoning.

Many hypotheses exist regarding the mechanism underlying delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), including the inflammation and immune-mediated damage hypothesis and the cellular apoptosis and direct neuronal toxicity hypothesis; however, no existing hypothesis provides a satisfactory explanation for the complex clinical processes observed in DEACMP. Leucine-rich repeat and immunoglobulin-like domain-containing protein-1 (LINGO-1) activates the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway, which negatively regulates oligodendrocyte myelination, axonal growth, and neuronal survival, causing myelin damage and participating in the pathophysiological processes associated with many central nervous system diseases. However, whether LINGO-1 is involved in DEACMP remains unclear. A DEACMP model was established in rats by allowing them to inhale 1000 ppm carbon monoxide gas for 40 minutes, followed by 3000 ppm carbon monoxide gas for an additional 20 minutes. The results showed that compared with control rats, DEACMP rats showed significantly increased water maze latency and increased protein and mRNA expression levels of LINGO-1, RhoA, and ROCK2 in the brain. Compared with normal rats, significant increases in injured neurons in the hippocampus and myelin sheath damage in the lateral geniculate body were observed in DEACMP rats. From days 1 to 21 after DEACMP, the intraperitoneal injection of retinoic acid (10 mg/kg), which can inhibit LINGO-1 expression, was able to improve the above changes observed in the DEACMP model. Therefore, the overexpression of LINGO-1 appeared to increase following carbon monoxide poisoning, activating the RhoA/ROCK2 signaling pathway, which may be an important pathophysiological mechanism underlying DEACMP. This study was reviewed and approved by the Medical Ethics Committee of Xiangya Hospital of Central South Hospital (approval No. 201612684) on December 26, 2016.

Predictive Values of Serum Biochemical Markers and Apparent Diffusion Coefficient on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

To explore the predictive values of serum biochemical markers and apparent diffusion coefficient (ADC) on delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Seventy-nine patients were divided into two groups based on the onset of DEACMP 60 days after with acute carbon monoxide poisoning. The baseline data of ACMP patients were collected. Serum levels of cardiac troponin I (cTNI), lactic acid (Lac), carboxyhemoglobin (COHb), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), and neuron-specific enolase (NSE) were measured within 24 hours of ACMP onset. The ADC of globus pallidum, centrum semiovale, and periventricular white matter were recorded by diffusion-weighted magnetic resonance imaging (DW-MRI) within 48 hours of admission. Logistic regression analysis was performed to determine the risk factors for DEACMP. The incidence of coma and duration of poisoning in the DEACMP group were significantly higher than those in the non-DEACMP group. The levels of Lac, CK, CK-MB, LDH, CRP and NSE in the DEACMP group were higher than those in the non- DEACMP group. The ADC value of globus pallidus in the DEACMP group was significantly higher than that in non-DEACMP group. The duration of poisoning, coma degree, CK, LDH, NES, and CRP were closely associated with the occurrence of DEACMP. The duration of poisoning, coma degree, and serum levels of CK, LDH, CRP, and NSE were independent risk factors for DEACMP.