Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Efficacy and safety of short-term edaravone or nerve growth factor add-on therapy for alcohol-related brain damage: A multi-centre randomised control trial.

AIMS: To measure the therapeutic effect of an anti-oxidant, edaravone (EDV), or neurotrophic treatment with nerve growth factor (NGF) as an add-on treatment for alcohol-related brain damage (ARBD). DESIGN: Multi-centre, randomised, single-blinded, comparative clinical trial. SETTING AND PARTICIPANTS: One hundred and twenty-two inpatients recruited from seven hospitals in different regions of China, all diagnosed with ARBD and aged 18 to 65 years old; among them, only two were female. INTERVENTION AND COMPARATOR: Patients were randomly assigned to receive one of three treatments for 2 weeks: 40 patients, treatment as usual (TAU: a combination of intramuscular injections of thiamine, intravenous infusions of other B vitamins with vitamin C and oral medication with vitamin E per day); 40, EDV add-on treatment to TAU (intravenous infusion with 30 mg of EDV twice per day); and 42, NGF add-on treatment to TAU (intramuscular injection of 20 µg of NGF per day). The patients underwent follow-up for 24 weeks. MEASUREMENTS: The primary outcome was the composite score of executive cognitive function in the 2nd week after treatment, which was measured as the mean of the Z scores of the assessments, including the digit symbol substitute test (DSST), digit span memory test-forward (DST-F), digit span memory test-reverse (DST-R) and space span memory test (SSMT). The secondary outcomes were the composite scores at later follow-ups, the score for each component of cognitive function, global cognitive function measured by the Montreal Cognitive Assessment (MoCA), craving for alcohol and the safety of the therapies. FINDINGS: EDV add-on treatment improved the composite score of executive cognitive function better than TAU in the 2nd week (adjusted mean difference: 0.24, 95% confidence interval 0.06 to 0.41; P = 0.008), but NGF add-on treatment did not (adjusted mean difference: 0.07, 95% confidence interval -0.09 to 0.24; P = 0.502). During the follow-up to 24 weeks, EDV add-on treatment improved the composite score of executive cognitive function and DST-R score better than TAU (both P < 0.01). Craving for alcohol was relieved in all three groups. No severe adverse events were observed. CONCLUSION: The short-term addition of edaravone to supplementary therapy treatment for alcohol-related brain damage (ARBD) improved executive cognitive function in patients with ARBD.

Microglia Autophagy Mediated by TMEM166 Promotes Ischemic Stroke Secondary to Carotid Artery Stenosis.

Ischemic stroke can be a serious complication of selective carotid endarterectomy (CEA) in patients with carotid artery stenosis (CAS). The underlying risk factors and mechanisms of these postoperative strokes are not completely understood. Our previous study showed that TMEM166-induced neuronal autophagy is involved in the development of secondary brain injury following cerebral ischemia-reperfusion injury in rats. This current study aimed to investigate the role of TMEM166 in ischemic stroke following CEA. In the clinical part of this study, the quantitative analysis demonstrated circulating TMEM166, interleukin 6 (IL-6), and C-reactive protein (CRP) levels were significantly elevated in patients who suffered an ischemic stroke after CEA compared to those who did not. Furthermore, non-survivors exhibited higher levels of these proteins than survivors. In the preclinical part of this study, a middle cerebral artery occlusion (MCAO) model was implemented following CAS simulation in TMEM166-/- mice. We found TMEM166 expression was positively correlated with the degree of ischemic brain injury. Ad5-TMEM166 transfection aggravated ischemic brain injury by inducing microglial autophagy activation and release of inflammatory cytokines. Accordingly, TMEM166 deficiency reduced brain inflammation and inhibited excessive microglial autophagy through the mammalian target of rapamycin (mTOR) pathway. These findings suggest that TMEM166 may play a key role in the development of ischemic injury after CEA and may serve as a biomarker for risk assessment of postoperative ischemic stroke.

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Purpose: We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity. Methods: We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis. Results: Compared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p < 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 109/L, p < 0.001), and neutrophil count (median 6.14 vs. 3.1 × 109/L, p < 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p < 0.001), blood WBC count (median 9.70 vs. 7.70 × 109/L, p < 0.001), neutrophil count (median 7.50 vs. 4.80 × 109/L, p < 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 109/L, p < 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018-6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64-0.80, p < 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705). Conclusion: Serum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Comparative analysis of clinical and imaging data of first-attack neuromyelitis optica spectrum disorders with and without connective tissue disease.

Background: The coexistence of neuromyelitis optica spectrum disorder (NMOSD) and connective tissue disease (CTD) is well recognized. The purpose of this study was to investigate and compare the characteristics of first attack NMOSD with and without CTD. Methods: A total of 113 Patients with NMOSD were included and were divided into two groups based on the presence of co-occurring CTD. Their demographic, clinical, laboratory, and image characteristics were obtained through inpatient medical records and follow-ups. Kaplan-Meier survival analysis was used to analyze the effect of CTD in NMOSD patients at the time of first recurrence. The risk factors that could predict complications of NMOSD with CTD was analyzed by binary logistic regression. The ability of homocysteine (Hcy) to predict the coexistence of NMOSD and CTD was analyzed and evaluated by the receiver operating characteristic curve. Results: The demographic data, clinical features, cerebrospinal fluid analysis, and MRI findings, except relapse events (including relapse rate, number of recurrences, and time of first recurrence), were similar between the two groups. The serum lymphocyte-to-monocyte ratio and albumin levels were lower (P < 0.05), while serum erythrocyte sedimentation rate and Hcy levels were higher in patients with NMOSD with CTD than in those without CTD (P < 0.001). Kaplan-Meier survival analysis showed that the time of first recurrence in NMOSD patients complicated with CTD was earlier than that of without CTD (log rank test P = 0.035). Logistic regression revealed that serum Hcy levels (OR 1.296, 95% CI, 1.050-1.601, P = 0.016) were independently associated with the occurrence of NMOSD with CTD. The receiver operating characteristic curve area was 0.738 (95% CI, 0.616-0.859; P < 0.001) for Hcy levels. Considering the Hcy concentration of 14.07 µmol/L as the cutoff value, the sensitivity and specificity of predicting the coexistence of first-attack NMOSD and CTD were 56 and 89.8%, respectively. Conclusions: When the first-attack NMOSD patients are complicated with CTD, they have a higher recurrence rate, more recurrences, earlier first recurrence, higher serum Hcy levels, and enhanced systemic inflammatory reactions. Furthermore, Hcy levels may help to screen for CTD in patients with first-attack NMOSD.

The altered functional connectivity density related to cognitive impairment in alcoholics.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain's "scale-free" networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke.

BACKGROUND: Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment. RESULTS: The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe2+, while acid-responsively liberating CAT to synergistically scavenge multiple ROS (·OH, ·O2-, and H2O2). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities. CONCLUSIONS: The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.

TNF-α (G-308A) Polymorphism, Circulating Levels of TNF-α and IGF-1: Risk Factors for Ischemic Stroke-An Updated Meta-Analysis.

Objective: Accumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-α gene promoter region and increased levels of TNF-α were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-α and IGF-1 with IS in different ethnic backgrounds and different sourced specimens. Methods: In this study, we examined whether rs1800629 genetic variant and levels of TNF-α and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria. Results: A total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS pathogenesis. Conclusion: Our findings demonstrated that the TNF-α rs1800629 polymorphism, the increased levels of TNF-α, and decreased levels of IGF-1 were involved in the etiology of IS.

Potential nanotherapeutic strategies for perioperative stroke.

AIMS: Based on the complex pathological environment of perioperative stroke, the development of targeted therapeutic strategies is important to control the development of perioperative stroke. DISCUSSIONS: Recently, great progress has been made in nanotechnology, and nanodrug delivery systems have been developed for the treatment of ischemic stroke. CONCLUSION: In this review, the pathological processes and mechanisms of ischemic stroke during perioperative stroke onset were systematically sorted. As a potential treatment strategy for perioperative stroke, the review also summarizes the multifunctional nanodelivery systems based on ischemic stroke, thus providing insight into the nanotherapeutic strategies for perioperative stroke.

Altered Global Signal Topography in Alcohol Use Disorders.

The most common symptom of patients with alcohol use disorders (AUD) is cognitive impairment that negatively affects abstinence. Presently, there is a lack of indicators for early diagnosis of alcohol-related cognitive impairment (ARCI). We aimed to assess the cognitive deficits in AUD patients with the help of a specific imaging marker for ARCI. Data-driven dynamic and static global signal topography (GST) methods were applied to explore the cross-talks between local and global neuronal activities in the AUD brain. Twenty-six ARCI, 54 AUD without cognitive impairment (AUD-NCI), and gender/age-matched 40 healthy control (HC) subjects were recruited for this study. We found that there was no significant difference with respect to voxel-based morphometry (VBM) and static GST between AUD-NCI and ARCI groups. And in dynamic GST measurements, the AUD-NCI patients had the highest coefficient of variation (CV) at the right insula, followed by ARCI and the HC subjects. In precuneus, the order was reversed. There was no significant correlation between the dynamic GST and behavioral scores or alcohol consumption. These results suggested that dynamic GST might have potential implications in understanding AUD pathogenesis and disease management.

Neurofilament Light Chain as a Biomarker for Monitoring the Efficacy of Transcranial Magnetic Stimulation on Alcohol Use Disorder.

OBJECTIVE: This study assessed the effects of repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on serum neurofilament light chain (NfL) levels, alcohol consumption, craving, and psychological impairment in participants with alcohol use disorder (AUD). METHODS: Participants with AUD were randomly assigned to receive one of two treatments (active or sham rTMS). All participants received 10 daily active or sham rTMS sessions over the left DLPFC for 2 weeks, with follow-up visits at baseline and immediately after the completion of the treatments. Serum samples were obtained before and after the intervention. Days of heavy drinking, visual analog scale (VAS) scores, and mental health component scores (MCSs) of the Medical Outcomes Study 36-Item Short Form Health Survey were used to assess the effects of rTMS. RESULTS: Active rTMS had a significant effect on reducing days of heavy drinking, alcohol craving, and serum NfL levels, and improved social functioning and mental health. The improvement with active rTMS was significantly greater than that with sham rTMS. Correlation analysis revealed that the reduction in the baseline drinking level was positively correlated with declines in the VAS and NfL levels but not with psychological scores. CONCLUSION: Repetitive transcranial magnetic stimulation of the left DLPFC was associated with reducing alcohol consumption and craving in patients with AUD and positively impacted neuropsychological and social function. Serum NfL levels may be useful as an early serological indicator of alcohol-induced brain injury.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

Comparative analysis of clinical and imaging data between patients with myelin oligodendrocyte glycoprotein antibody disease and patients with aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder.

BACKGROUND: We aimed to compare the clinical data, laboratory findings, and imaging characteristics of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin 4 antibody (AQP4)-positive neuromyelitis optica spectrum disorder (NMOSD), as detailed comparative analyses of laboratory data for both diseases are rare. METHODS: Our retrospective study compared the clinical data, laboratory findings, and imaging characteristics of 118 AQP4-positive patients with first-episode NMOSD and 25 patients with first-episode MOGAD. Logistic regression was used to determine the factors that differentiated MOGAD and AQP4-positive NMOSD. RESULTS: There were significant differences in age, symptoms, recurrence rate, laboratory indicators, and imaging examinations between patients with MOGAD and patients with AQP4-positive NMOSD. Patients with MOGAD were younger and had higher levels of uric acid than those with AQP4-positive NMOSD. The proportion of cortical gray matter/juxtacortical white matter lesions was significantly higher in the MOGAD group than in the NMOSD group. Logistic regression revealed that young age [odds ratio (OR) = 0.947, 95% confidence interval (CI) = 0.905-0.99], high uric acid level (OR = 1.016, 95% CI = 1.006-1.027), and cortical gray matter/juxtacortical white matter involvement (OR = 3.889, 95% CI = 1.048-14.442) were significantly related to MOGAD. CONCLUSION: The multivariate analysis of the present study demonstrated that age, uric acid level, and the presence of lesions in the cortical gray matter/juxtacortical white matter can aid in distinguishing patients with AQP4-positive NMOSD from those with MOGAD. These factors may also aid in determining which patients should be tested for antibodies.

Neurofilament Light Chain Is a Promising Biomarker in Alcohol Dependence.

Background: Alcohol dependence, a global public health problem, leads to structural and functional damage in the brain. Alcohol dependence patients present complex and varied clinical manifestations and live with general complaints existing in contemporary society, making most people with alcohol dependence hard to identify. Therefore, it is important to find potential biomarkers for the diagnosis and evaluation of alcohol dependence. In the study, we explored potential biomarkers for the diagnosis and monitoring of diseases and evaluated brain structural changes in alcohol dependence patients. Methods: Enzyme-linked immunosorbent assay (ELSA) was employed to detect the expression of serum nucleotide-binding oligomerization domain containing 3 (NLRP3) and single-molecule array (Simoa) assay was used to detect the expression of serum neurofilament light (NfL) in 50 alcohol dependence patients and 50 controls with no drinking history. Alcohol consumption was measured by standard drinks. Neuropsychological assessments, including the Montreal cognitive assessment (MoCA), Pittsburgh sleep quality index (PSQI), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9), were conducted to evaluate cognitive function and psychological state. The degree of white matter lesions (WMLs) was rated using the Fazekas scale based on magnetic resonance imaging analysis. White matter structure was quantified using the voxel-based morphometry method. The correlations between NLRP3 levels, NfL levels, neuropsychological dysfunction, the degree of WMLs, and white matter volume (WMV) were analyzed in alcohol dependence patients. Results: Serum NLRP3 and NfL levels were higher in the alcohol dependence group. NLRP3 levels were irrelevant to monthly alcohol assumption as well as to the MoCA, PSQI, GAD-7, PHQ-9, and Fazekas scale scores and WMV. NfL levels were positively correlated with the PSQI and PHQ-9 scores as well as the degree of WMLs and negatively correlated with the MoCA scores and WMV. No associations were evident between NfL and monthly alcohol assumption and GAD-7 scores in the alcohol dependence group. Conclusion: This study supports the potential value of serum NfL as a non-invasive biomarker in alcohol dependence. The association with neuropsychological dysfunction and degree of WMLs has implications to use NfL as a promising biomarker to assess the severity of brain damage as well as the progression and prognosis of alcohol dependence.

Monocyte to High-Density Lipoprotein Ratio: A Novel Predictive Marker of Disease Severity and Prognosis in Patients With Neuromyelitis Optica Spectrum Disorders.

Background and Purpose: To investigate the association of monocyte to high-density lipoprotein ratio (MHR) with disease severity and prognosis in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: This retrospective study included 125 patients with NMOSD. Demographic and clinical parameters, including the MHR, were assessed. The initial Expanded Disability Status Scale (EDSS) score and relapse rate were used to evaluate disease severity and prognosis, respectively. Correlations between MHR and disease severity and relapse rate were analyzed. The predictive value of MHR for prognosis was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Compared with the low MHR group, the initial EDSS score (median 4.5 vs. 5.5%, P = 0.025) and relapse rate (51.61 vs. 30.16%, P = 0.015) were significantly higher in the high MHR group. MHR was positively correlated with the initial EDSS score (r = 0.306, P = 0.001). Multivariate analysis showed that MHR was significantly associated with severity (odds ratio = 7.90, 95% confidence interval [CI] = 1.08-57.82, P = 0.041), and it was a significant predictor of disease prognosis (hazard ratio = 3.12, 95% CI = 1.02-9.53, P = 0.046). The median relapse interval of the high MHR group was 24.40 months. When the MHR was higher than 0.565, the risk of relapse was high [sensitivity, 33.3%; specificity, 91.9%; area under the ROC curve, 0.642 (95% CI = 0.54-0.74, P = 0.007)]. Conclusion: MHR is a novel predictive marker of disease severity and prognosis in patients with NMOSD. Early monitoring and reduction of MHR may allow earlier intervention and improved prognosis.

Association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of first attack neuromyelitis optica spectrum disorder (NMOSD): a retrospective cohort study.

BACKGROUND: To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and prognosis after the first attack of optic neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this retrospective study, we included the medical records of 324 patients with first episode NMOSD and collected data on clinical parameters. Follow-up extended disability status scale (EDSS) score and relapse rate were analyzed using logistic regression models to determine the independent effect of NLR on outcomes; receiver operating characteristic (ROC) curves were applied to analyze the predictive value of NLR for the prognosis of NMOSD. Interaction and stratification analyses were used to explore the association between NLR and prognosis of patients with NMOSD, and Kaplan-Meier analysis was used to investigate the relationship between NLR and outcome. The association between NLR level with relapse rate and poor recovery was assessed by a Cox regression analysis. RESULTS: Patients in the high-NLR group had significantly higher EDSS scores and relapse rates at follow-up (both, P < 0.001) than did those in the low-NLR group. Univariate analysis showed revealed that NLR was significantly associated with relapse (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.16-1.41, P < 0.001) and poor recovery (OR = 1.32, 95% CI: 1.20-1.46, P < 0.001), and these associations remained significant, even after multifactorial analysis (OR = 1.33, 95% CI: 1.11-1.59, P = 0.002; OR = 1.23, 95% CI: 1.06-1.43, P = 0.007, respectively). Stratified analysis showed that sex, platelet-to-lymphocyte ratio (PLR) level, and lymphocyte-to-monocyte technical ratio (LMR) level were strongly associated with relapse owing to elevated NLR; Kaplan-Meier survival curve analysis showed that the median time to relapse was significantly lower in the high-NLR group than in the low-NLR group (P < 0.001). A multivariate analysis showed a significant relationship between NLR level with relapse (HR = 1.07, 95%CI: 1.03-1.10, P = 0.001) and poor recovery (HR = 1.08, 95%CI: 1.04-1.11, P = 0.001). CONCLUSIONS: NLR may be used as a prognostic indicator for first onset NMOSD, and a high NLR may be significantly associated with high relapse rates and poor recovery.

Effect of Low Complement C4 on Clinical Characteristics of Patients with First-Episode Neuromyelitis Optica Spectrum Disorder.

PURPOSE: To describe and compare the clinical features of patients with first-episode neuromyelitis optica spectrum disorder (NMOSD) in a normal complement C4 group and a low complement C4 group, and explore the mechanism by which low complement C4 affects the clinical features of patients with NMOSD. PATIENTS AND METHODS: We retrospectively analyzed clinical data of 169 aquaporin-4 (AQP4) antibody positive patients with NMOSD from the First Affiliated Hospital of Zhengzhou University from December 2013 to March 2021. Prior to treatment, the blood was drawn for detection, and the patients underwent a 3.0 Tesla MRI examination. A low complement C4 level was defined as a serum complement C4 level <0.14 g/L. Depending on whether the complement C4 level was reduced, it was divided into the normal complement C4 group and low complement C4 group. The basic demographics, clinical manifestations, laboratory examinations, and imaging findings of the two groups were compared. RESULTS: Among the 169 AQP4 antibody positive patients, 54 were low-complement C4 patients and 115 were normal. There were no significant differences in the demographics, clinical manifestations, treatment options, or admission Expanded Disability Status Scale (EDSS) score between two groups (P > 0.05). The median of discharged EDSS was the same (4 vs 4), but the difference between the two was statistically significant (P = 0.019). Compared with the normal complement C4 group, the blood uric acid level (225 vs 179; P = 0.001) and the C3 level (1.06 vs 0.87, P = 0.000) of the low complement C4 group were significantly lower. The incidence of brainstem lesions in patients with low complement C4 was higher (53.7% vs 33%, P = 0.01). CONCLUSION: The treatment effect of the first-episode AQP4 antibody positive NMOSD low complement C4 group was poor, the blood-brain barrier was more severely damaged, and the disease changes were likely to involve the brainstem.

Analysis of Predictive Risk Factors in Aquaporin-4-IgG Positive Highly Active Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory diseases with a high risk of recurrence and progressive disability, and it is crucial to find sensitive and reliable biomarkers for prognosis and the early prediction of relapse. Highly active NMOSD is defined as two or more clinical relapses within a 12-month period. In this study, we analyzed independent risk factors among patients with aquaporin-4 (AQP4)-IgG positive highly active NMOSD. In this retrospective study, we analyzed the data of 94 AQP4-IgG positive patients with highly active NMOSD and 105 AQP4-IgG positive controls with non-highly active NMOSD. In order to rule out possible effects of previous treatments (such as glucocorticoids, immunoglobulin, and immunosuppressants), we focused on the first-attack NMOSD patients admitted to our hospital. Clinical data, including the age of onset, gender, comorbidities, and serum analysis and cerebrospinal fluid (CSF) analysis results, were collected, after which logistic regression models were used to determine the associations between the clinical factors and relapse outcomes. The prevalence of connective tissue disease and the proportion of antinuclear antibody (ANA)-positivity were higher in the highly active NMOSD group than in the control group. The leukocyte counts, homocysteine (Hcy) levels, CSF leukocyte counts, protein concentrations, IgG indexes, and 24h IgG synthesis rates were also higher in the highly active NMOSD group. The results of multivariate analysis indicated that connective tissue disease comorbidity (OR = 5.953, 95% CI: 1.221-29.034, P = 0.027), Hcy levels (OR = 1.063, 95% CI: 1.003-1.126, P = 0.04), and 24h IgG synthesis rate (OR = 1.038, 95% CI: 1.003-1.075, P = 0.034) may be independent risk factors for AQP4-IgG positive highly active NMOSD relapse after adjusting for various variables. Comorbidity of connective tissue disease, Hcy levels, and 24h IgG synthesis rate may be independent risk factors for AQP4-IgG positive highly active NMOSD.

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders.

Background: Many patients with neuromyelitis optica spectrum disorders (NMOSD) experience the adverse consequences of relapse and disability aggravation. Thus, it is necessary to identify sensitive and reliable biomarkers for early prognosis. This study investigated whether serum homocysteine (Hcy) level was associated with the risk of relapse or poor prognosis in first-attack NMOSD patients. Methods: We enrolled 161 first-attack NMOSD patients in this retrospective study. We reviewed their medical records and evaluated their initial Expanded Disability Status Scale (EDSS). Clinical outcomes were measured by the final EDSS and the relapse rate. The association between Hcy levels and EDSS score at last follow-up was analyzed by binary logistic regression. The association between Hcy levels and relapse rate was assessed by Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was used to predict the target value of Hcy reduction. Results: Compared with the high Hcy group, the final EDSS score in the low Hcy group was significantly lower (median: 0.5 vs. 2.5, P < 0.001). The relapse rate differed significantly between these groups (30.6 vs. 50.0%, P = 0.023). Multivariate analysis showed that the initial EDSS score (odds ratio [OR] 3.03, 95% confidence interval [CI] 2.07-4.45, P < 0.001) and serum Hcy level (OR 1.13, 95%CI 1.04-1.22, P = 0.002) were significantly associated with poor prognosis in NMOSD patients. Additionally, multivariate analysis showed that serum Hcy level (hazard ratio 1.06, 95%CI 1.04-1.09, P < 0.001) was an independent predictor of the risk for relapse in NMOSD. The 12-month relapse rate of the high Hcy group was 34.8%, and 50% of high Hcy patients relapsed within 35 months after the first onset. A serum Hcy level exceeding 14.525 µmol/L indicated a high risk of relapse, with a sensitivity of 43.7%, specificity of 90.0%, and area under the ROC curve of 0.674 (95%CI 0.59-0.76, P < 0.001). Conclusion: Serum Hcy level is an independent predictor of relapse and poor prognosis in first-attack NMOSD patients. Early monitoring and reduction of serum Hcy levels may be of great significance in the prevention of disease relapse and severe disability.