Autoimmune encephalitis antibody profiles and clinical characteristics of children with suspected autoimmune encephalitis.

AIM: To identify the spectrum of autoimmune encephalitis antibody biomarkers (AE-Abs) in children with suspected autoimmune encephalitis and explore the clinical features indicating AE-Abs presence. METHOD: We included children with suspected autoimmune encephalitis who underwent AE-Abs tests at the Children's Hospital of Chongqing Medical University between June 2020 and June 2022. Clinical features suggestive of AE-Abs were analysed based on AE-Abs test results. RESULTS: A total of 392 children were tested for AE-Abs with suspected autoimmune encephalitis. Of these, 49.5% were male, with a median age of 7 years 11 months (6 months-17 years 11 months); 93.6% (367/392) of all patients had both serum and cerebrospinal fluid (CSF) tests performed. The antibody-positive rate in the cohort was 23.7% (93/392), the serum antibody-positive rate was 21.9% (84/384), and the CSF antibody-positive rate was 20.8% (78/375). Eleven different AE-Abs were detected. Serum analysis revealed that N-methyl-D-aspartate receptor immunoglobulin-G (NMDAR-IgG) (15.1%) was greater than myelin oligodendrocyte glycoprotein (MOG)-IgG (14.6%) and glial fibrillary acidic protein (GFAP)-IgG (3.3%). CSF analysis revealed that NMDAR-IgG (16.3%) was greater than MOG-IgG (13.8%) and GFAP-IgG (3.3%). Compared with antibody-negative patients, antibody-positive patients were more often female (odds ratio [OR] 1.86, p = 0.03), with memory impairment (OR 2.91, p = 0.01) and sleep disorders (OR 2.08, p = 0.02). INTERPRETATION: In children, the most frequent AE-Abs detected were NMDAR-IgG and MOG-IgG. Female sex, memory impairment, and sleep disorders predict a higher likelihood of AE-Abs.

TREM2 mitigates NLRP3-mediated neuroinflammation through the NF-κB and PI3k/Akt signaling pathways in juvenile rats exposed to ambient particulate matter.

Ambient particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological disorders that typically involve neuroinflammation. There have been few studies on the effect of PM on neuroinflammation to date. In this study, we used a juvenile rat model (PM exposure was conducted at a dose of 10 mg/kg body weight per day for 4 weeks) and a BV-2 cell model (PM exposure was conducted at concentrations of 50, 100, 150, and 200 µg/ml for 24 h) to investigate PM-induced neuroinflammation mediated by NLRP3 inflammasome activation and the role of TREM2 in this process. Our findings revealed that PM exposure reduced TREM2 protein and mRNA levels in the rat hippocampus and BV-2 cells. TREM2 overexpression attenuated PM-induced spatial learning and memory deficits in rats. Moreover, we observed that TREM2 overexpression in vivo and in vitro effectively mitigated the increase in NLRP3 and pro-Caspase1 protein expression, as well as the secretion of IL-1ß and IL-18. Exposure to PM increased the expression of NF-κB and decreased the phosphorylation of PI3k/Akt in vivo and in vitro, and this process was effectively reversed by overexpressing TREM2. Our results indicated that PM exposure could reduce TREM2 expression and induce NLRP3 inflammasome-mediated neuroinflammation and that TREM2 could mitigate NLRP3 inflammasome-mediated neuroinflammation by regulating the NF-κB and PI3k/Akt signaling pathways. These findings shed light on PM-induced neuroinflammation mechanisms and potential intervention targets.

Depression associated with dietary intake of flavonoids: An analysis of data from the National Health and Nutrition Examination Survey, 2007-2010.

BACKGROUND: Flavonoids may have a protective effect against depression. The purpose of this study was to examine whether flavonoid intake was associated with depression. METHODS: This is an observational cross-sectional study. We evaluated a sample of 8183 adults from the National Health and Nutrition Examination Survey (NHANES), 2007-2010. The participants had an average age of 46.7 years, and 48.4% of them were male. Flavonoid intake was obtained through dietary recall interviews, and it included six subclasses: isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols. Depression was identified using the Patient Health Questionnaire (PHQ-9). Logistic regression was utilized to evaluate the association between flavonoid intake and depression. Restricted cubic splines (RCS) were utilized to investigate nonlinear associations. Differences between subgroups were explored. Mediation analysis was used to explore confounding/mediating factors. These models were adjusted for age, sex, race/ethnicity, poverty status, education, smoking status, alcohol consumption, BMI, energy intake, physical activity, and chronic diseases. RESULTS: There were 765 individuals with depression (PHQ-9 score ≥ 10) in the sample. After adjusting for covariates, flavanones, flavones, and total flavonoid intake were associated with a lower likelihood of depression (OR (95% CI): 0.73(0.64,0.84); 0.36(0.21,0.63); 0.86(0.74,0.99), respectively). A significant inverse correlation was observed between flavonoid consumption and the somatic symptom score of the PHQ-9. We observed a stronger association between flavonoids and depression in non-Hispanic white groups. The relationship between the total flavonoid intake and depression was explained to some extent by sleep duration (13.8%). CONCLUSIONS: Flavonoid intake was associated with lower odds of depression.

ATP1A3-related phenotypes in Chinese children: AHC, CAPOS, and RECA.

The aim of this research is to study the phenotype, genotype, treatment strategies, and short-term prognosis of Chinese children with ATP1A3 (Na+/K+-ATPase alpha 3 gene)-related disorders in Southwest China. Patients with pathogenic ATP1A3 variants identified using next-generation sequencing were registered at the Children's Hospital of Chongqing Medical University from December 2015 to May 2019. We followed them as a cohort and analyzed their clinical data. Eleven patients were identified with de novo pathogenic ATP1A3 heterozygous variants. One (c.2542 + 1G > T, splicing) has not been reported. Eight patients with alternating hemiplegia of childhood (AHC), one with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), and two with relapsing encephalopathy with cerebellar ataxia (RECA) were included. The initial manifestations of AHC included hemiplegia, oculomotor abnormalities, and seizures, and the most common trigger was an upper respiratory tract infection without fever. All patients had paroxysmal hemiplegic attacks during their disease course. The brain MRI showed no abnormalities. Six out of eight AHC cases reached a stable disease state after treatment. The initial symptom of the patient with CAPOS was ataxia followed by developmental regression, seizures, deafness, visual impairment, and dysarthria, and the brain MRI indicated mild cerebellar atrophy. No fluctuation was noted after using Acetazolamide. The initial manifestations of the two RECA cases were dystonia and encephalopathy, respectively. One manifested a rapid-onset course of dystonia triggered by a fever followed by dysarthria and action tremors, and independent walking was impossible. The brain MRI image was normal. The other one presented with disturbance of consciousness, seizures, sleep disturbance, tremor, and dyskinesias. The EEG revealed a slow background (δ activity), and the brain MRI result was normal. No response to Flunarizine was noted for them, and it took 61 and 60 months for them to reach a stable disease state, respectively. CONCLUSION: Pathogenic ATP1A3 variants play an essential role in the pathogenesis of Sodium-Potassium pump disorders, and AHC is the most common phenotype. The treatment strategies and prognosis depend on the phenotype categories caused by different variation sites and types. The correlation between the genotype and phenotype requires further exploration. WHAT IS KNOWN: • Pathogenic heterozygous ATP1A3 variants cause a spectrum of neurological phenotypes, and ATP1A3-disorders are viewed as a phenotypic continuum presenting with atypical and overlapping features. • The genotype-phenotype correlation of ATP1A3-disorders remains unclear. WHAT IS NEW: • In this study, the genotypes and phenotypes of ATP1A3-related disorders from Southwest of China were described. The splice-site variation c.2542+1G>T was detected for the first time in ATP1A3-related disorders. • The prognosis of twins with AHC p. Gly947Arg was more serious than AHC cases with other variants, which was inconsistent with previous reports. The phenomenon indicated the diversity of the correlation between the genotype and phenotype.

Autoimmune encephalitis after Japanese encephalitis in children: A prospective study.

OBJECTIVE: To explore anti-neuronal surface antibodies and identify associated serum predictors of autoimmune encephalitis after Japanese encephalitis (JE). METHODS: This prospective study first detected anti-neuronal surface antibodies and cytokines in the serum and cerebrospinal fluid (CSF) of JE patients within one week of symptom onset. Anti-neuronal surface antibodies and cytokines in the serum were detected on day 21 post-JE. If the patients relapsed during the convalescent phase, we simultaneously detected JE virus RNA and cytokines in the CSF, as well as anti-neuronal surface antibodies in the serum and CSF. RESULTS: All 31 patients were negative for anti-neuronal surface antibodies at the onset of JE in the serum and CSF. During the convalescent phase, five patients developed autoimmune encephalitis (two had anti-N-methyl-d-aspartate receptor [NMDAR] antibodies, one had γ-aminobutyric acid-B receptor [GABABR] antibodies, and two had other antibodies against unknown neuronal surface antigens). Patients who developed autoimmune encephalitis experienced more severe outcomes than those who did not at the one-year follow-up (p = 0.044). The levels of serum CXCL13 and IL-6, as well as CXCL13, BAFF, CXCL10, and MMP-9 in the CSF were increased in the convalescent phase compared to the acute phase in patients who developed autoimmune encephalitis (p < 0.05). CONCLUSION: In addition to anti-NMDAR antibodies, anti-GABABR antibodies and antibodies against unknown neuronal surface antigens can trigger autoimmune encephalitis following JE. Patients who developed autoimmune encephalitis had a poorer prognosis at the one-year follow-up. Serum CXCL13 may represent a predictor of autoimmune encephalitis after JE.