Less common phenotypes of myelin oligodendrocyte glycoprotein antibody-related diseases in children deserve more attention.

BACKGROUND: To facilitate the identification of less common clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children. METHODS: We retrospectively reviewed medical records of 236 patients with MOGAD. The following phenotypes were considered to be typical for MOGAD: ADEM, ON, TM, and NMOSD. Less common onset clinical phenotypes were screened out; their clinical and magnetic resonance imaging (MRI), diagnosis, treatment, and prognosis were summarized and analyzed. RESULTS: 16 cases (6.8%) presented as cortical encephalitis, with convulsions, headache, and fever as the main symptoms. 15 cases were misdiagnosed in the early period. 13 cases (5.5%) showed the overlapping syndrome of MOGAD and anti-N-methyl-D aspartate receptor encephalitis (MNOS), with seizures (92.3%) being the most common clinical symptom. 11 cases (84.6%) showed relapses. The cerebral leukodystrophy-like phenotype was present in seven cases (3.0%), with a recurrence rate of 50%. Isolated seizures without any findings on MRI phenotype was present in three cases (1.3%), with the only clinical symptom being seizures of focal origin. Three cases (1.3%) of aseptic meningitis phenotype presented with prolonged fever. CONCLUSION: 40/236 (16.9%) of children with MOGAD had less common phenotypes. Less common clinical phenotypes of pediatric MOGAD are susceptible to misdiagnosis and deserve more attention. IMPACT: This is the first comprehensive analysis and summary of all less commonl clinical phenotypes of MOGAD in children, while previous studies have only focused on a specific phenotype or case reports. We analyzed the characteristics of MOGAD in children and further revealed the reasons why these less common clinical phenotypes are prone to misdiagnosis and deserve more attention. Our research on treatment has shown that early detection of MOG antibodies and early treatment are of great significance for improving the prognosis of these patients.

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.

Investigation of the response of Platycodongrandiflorus (Jacq.) A. DC to salt stress using combined transcriptomics and metabolomics.

BACKGROUND: Platycodon grandiflorus (Jacq.) A. DC is a famous traditional Chinese medicine in China and an authentic medicine in Inner Mongolia. It has been traditionally used as an expectorant in cough and also has anti-inflammatory and other pharmacological effects. As a homologous plant of medicine and food, P. grandiflorus is widely planted in Northeast China. Soil salinity isa limiting factor for its cultivation. In this study, we comprehensively described the physiological characteristics of P. grandiflorus and combined transcriptomics and metabolomics to study the response of roots of P. grandiflorus to salt stress. RESULTS: Overall, 8,988 differentially expressed genes were activated and significantly altered the metabolic processes. In total, 428 differentially abundant metabolites were affected by salt stress. After moderate and severe salt stress, most of the differentially abundant metabolites were enriched in the L-phenylalanine metabolic pathway. Through the comprehensive analysis of the interaction between key genes and metabolites, the main pathways such as lignin compound biosynthesis and triterpene saponin biosynthesis were completed. The relative content of compounds related to lignin biosynthesis, such as caffeic acid, coniferin, and syringing, increased under salt stress, and the related genes such as PAL, C4H, and the key enzyme gene UGT72E2 were activated to adapt to the salt stress. Platycodon saponin is one of the major triterpene saponins in P. grandiflorus, and Platycodin D is its most abundant major bioactive component. Under severe salt stress, Platycodin D level increased by nearly 1.77-fold compared with the control group. Most of the genes involved insynthetic pathway of Platycodin D, such as HMGCR, GGPS, SE, and LUP, were upregulated under salt stress. CONCLUSION: Salt stress led to a decrease in the biomass and affected the activities of antioxidant enzymes and contents of osmotic regulators in the plant. These results provided not only novel insights into the underlying mechanisms of response of P. grandiflorus to salt stress but also a foundation for future studies on the function of genes related to salt tolerance in the triterpenoid saponin biosynthesis pathway.

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.

Fulminant anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluR1 antibodies encephalitis in a Chinese boy: a case report.

BACKGROUND: Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a rare autoimmune synaptic encephalitis associated with autoantibodies that cause a selective decrease in surface expression and changes in receptor localization. Anti-AMPAR encephalitis is poorly recognized, especially in children, and its clinical phenotype is incompletely described. CASE PRESENTATION: We report a case of anti-AMPAR GluR1 antibody-mediated autoimmune encephalitis in a 12-year-old male. The patient manifested as a fulminant course, with ataxia, cerebellar degeneration at the onset, and rapidly evolved into hyperthermia, coma and rhabdomyolysis. Antibodies against AMPAR GluR1 receptors were detected in the cerebrospinal fluid by cell-based assay. Diffuse slow waves were found by electroencephalograph, and the left cerebellar vermis and hemisphere were affected on brain magnetic resonance imaging (MRI). The patient was treated with intravenous immunoglobulin (IVIG), methylprednisolone combined with plasma exchange. Symptoms were alleviated after immunotherapy and the patient sustained clinical improvement. This is the first time that acute rhabdomyolysis symptom has been identified in a pediatric patient with anti-AMPAR encephalitis. CONCLUSIONS: This case expands the clinical spectrum of anti-AMPAR encephalitis and highlights that despite poor clinical manifestation at the outset, recovery remains possible.

Chemical Constituents of Cyperus esculentus Leaves and the Protective Effect against Agricultural Fungicide-Induced Hepatotoxicity.

Cyperus esculentus is cultivated as a crop plant due to its edible and oily tubers (tiger nut). However, little is known about the phytochemicals and bioeffects of the leaves. This study was conducted to identify and quantify the chemical constituents of C. esculentus leaves and evaluate their bioactivities. By liquid chromatography-mass spectrometry, 30 compounds including flavan-3-ols, caffeic acid derivatives, and flavones, were identified from the leaves. The quantitative analysis revealed that gallocatechin (8), procyanidin B1 (15), catechin (16), chlorogenic acid (19), orientin (30), and luteolin 7-O-glucuronide (31) are the major chemical constituents of C. esculentus leaves. The contents of these six chemical constituents in the leaves collected in September in Hohhot, China, reached to 1460.85±7.66, 10178.77±302.65, 1048.35±17.37, 1722.15±26.13, 5318.62±277.16, and 1526.54±11.95 µg, respectively, in one gram of the dried leaves. The leaf extract (CELE) showed strong antioxidant activity in vitro, with compounds 8, 15, and 19 contributing the most. CELE showed significant protection against the agricultural fungicide tebuconazole-induced developmental toxicity and hepatotoxicity in zebrafish.

Prognostic factors for the recurrence of afebrile seizures after benign convulsions associated with mild gastroenteritis.

OBJECTIVE: The overall prognosis of benign convulsions associated with mild gastroenteritis (CwG) is favorable, and the incidence of afebrile seizure recurrence with or without gastroenteritis (ASwGI and ASwoGI, respectively) is low. In this study we investigated the prognostic factors associated with afebrile seizure (AS) relapse after the first CwG episode. METHODS: A hospital-based cohort with an initial CwG episode from January 2012 to October 2019 was followed for at least 19 months. The relapse types were divided into ASwGI and ASwoGI. Logistic regression analysis was performed to identify the independent prognostic factors for the recurrence of AS after the initial CwG episode. Furthermore, the clinical characteristics between ASwGI and ASwoGI were compared. RESULTS: Among the 868 patients enrolled, 67 (7.7%) experienced a second AS and 71% (48/67) showed gastroenteritis-associated recurrence. Except for five patients with subsequent epilepsy (0.6%), only eight (0.9%) experienced three seizure episodes. The independent predictive factors for the subsequent recurrence of AS were age less than 18 months at onset (odds ratio [OR]: 2.93, 95% confidence interval [CI]: 1.53-5.63), repeated seizures over 24 h (OR: 4.09, 95% CI: 2.19-7.65), and absence of fever (OR: 2.33, 95% CI: 1.26-4.33) during the first CwG episode. The probability of recurrence of AS for those with one, two, and three predictive factors was 3.23%, 13.35%, and 22.85%, respectively. In addition, the age at onset was significantly lower in the ASwoGI group than in the ASwGI group during the first episode (p < .05). SIGNIFICANCE: The risk of AS relapse after the initial CwG episode is low, and the majority of patients presented with gastroenteritis. The risk can be predicted by age at onset, repeated seizures over 24 h, and absence of fever during the first CwG episode.

Childhood ischaemic stroke in the basal ganglia can lead to fine motor and anxiety disorders: a retrospective analysis and follow-up of 109 cases.

BACKGROUND: Stroke in children easily causes long-term dysfunction. Whether the prognoses of motor and anxiety disorders are related to the affected stroke area has not been reported. METHODS: One hundred nine cases of children with ischaemic stroke were reviewed and divided into three groups: lenticular nucleus lesions only (lenticular nucleus group), lenticular nucleus and caudate head lesions (caudate head group), and lenticular nucleus and thalamus lesions (thalamus group). Overall prognosis was evaluated by the mRS score. The SCAS-P was used to evaluate anxiety in children aged ≥6 years. RESULTS: mRS scores were ≤ 2 points (mean: 0.62), no significant difference among groups. 3/21 (14.2%) patients in the caudate head group changed handedness, which is significantly higher than other groups. Patients with lesions in thalamus group had significantly higher SCAS-P scores. CONCLUSIONS: The overall prognosis of children with basal ganglia ischaemic stroke is good. However, hand preference changes and anxiety disorders may develop. Patients in the caudate head groups are more likely to suffer from fine motor disorders and changes in handedness. Patients within the thalamus group are more prone to anxiety than patients in the other groups. Anxiety disorders should be noted in children with basal ganglia stroke.

Characteristics and outcomes of children with dissociative (conversion) disorders in western China: a retrospective study.

BACKGROUND: Dissociative (conversion) disorder in children is a complex biopsychosocial disorder with high rates of medical and psychiatric comorbidities. We sought to identify the characteristics and outcomes of children with dissociative (conversion) disorders in western China. METHODS: We conducted a retrospective cohort study of 66 children admitted with dissociative (conversion) disorders from January 2017 to July 2019, and analyzed their clinical characteristics, socio-cultural environmental variables, and personality and psychiatric/psychological characteristics. Binary logistic regression was used to analyze the variables associated with clinical efficacy. RESULTS: Of these 66 patients, 38 (57.6%) were male and 28 (42.4%) were female, 46 (69.7%) had an antecedent stressor, 30 (45.5%) were left-behind adolescents, and 16 (24.2%) were from single-parent families. In addition, 30 patients (45.5%) were not close to their parents, 38 patients (59.4%) had an introverted personality, and 34 (53.1%) had unstable emotions. Thirteen families (19.7%) were uncooperative with the treatment. Patients who had cormorbid anxiety or depression exhibited significantly lower cognitive ability (P < 0.01). Logistic regression found that better treatment outcomes were positively associated with having a close relationship with parents, parental cooperation with treatment, and having a father with a lower level of education (i.e., less than junior college or higher). CONCLUSIONS: The characteristics and outcomes of children with dissociative (conversion) disorders are related to socio-cultural environmental variables and psychiatric/psychological factors. Timely recognition and effective treatment of dissociative (conversion) disorders are important.

Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency.

BACKGROUND: Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare urea cycle disorder. The aim of this study was to present the clinical findings, management, biochemical data, molecular genetic analysis, and short-term prognosis of five children with CPS1D. METHODS: The information of five CPS1D patients was retrospectively studied. We used targeted next-generation sequencing to identify carbamoyl phosphate synthetase 1 (CPS1) variants in patients suspected to have CPS1D. Candidate mutations were validated by Sanger sequencing. In silico and structure analyses were processed for the pathogenicity predictions of the identified mutations. RESULTS: The patients had typically clinical manifestations and biochemical data of CPS1D. Genetic analysis revealed nine mutations in the CPS1 gene, including recurrence of c.1145C > T, five of which were firstly reported. Seven mutations were missense changes, while the remaining two were predicted to create premature stop codons. In silico and structure analyses showed that these genetic lesions were predicted to affect the function or stability of the enzyme. CONCLUSION: We reported five cases of CPS1D. Five novel mutations of CPS1 gene were found. Mutations of CPS1 have private nature, and most of them are missense compound heterozygous. The mutation affecting residue predicted to interfere the catalytic sites, the internal tunnel, or the regulatory domain results in severe phenotype.

Hepato-protective effects and chemical constituents of a bioactive fraction of the traditional compound medicine-Gurigumu-7.

BACKGROUND: Gurigumu-7 is an important traditional Mongolian medicine frequently used for liver diseases. However, the pharmacological effects and the bioactive constituents are not well understood. METHOD: This research was to use CCl4-induced liver damage in mice to investigate the hepatoprotective effects of Gurigumu-7 and the methanol eluted fraction from a DIAION column of an extract of Gurigumu-7 (MF). The chemical constituents of MF were analyzed by UPLC-MS. RESULTS: Pretreated orally with MF (66, 132 and 264 mg/kg) once a day for 4 days dose-dependently suppressed CCl4-induced mice liver histopathological changes and serum aminotransferase activities (alanine transaminase: 1144.0 ± 787.2 v.s. 2461.8 ± 1072.7 U/L, p < 0.05; aspartate transaminase: 1173 ± 785.3 v.s. 2506.6 ± 1140.7 U/L, p < 0.01). MF treated group demonstrated increased levels of SOD (108.19 ± 30.32 v.s. 75.75 ± 5.37 U/mg protein, p < 0.01) but decreased levels of malonyldialdehyde (7.68 ± 1.95 v.s. 44.32 ± 16.68 nmol/mg protein, p < 0.01) compared to the CCl4 control group. More than 30 chemical constituents were quantified, and MF was found to be rich in ellagic acid (297.97 mg/g), luteolin and its glucosides (35.10 mg/g), apigenin and its glucosides (>30 mg/g), ursolic acid (14.91 mg/g), bidenoside C (8.75 mg/g), and proanthocyanidins (15.64 mg/g in proanthocyanidin A2 equivalent). CONCLUSION: The methanol eluted fraction (MF) from a DIAION column of an extract of the Mongolian medicine-Gurigumu-7 was found to be more hepatoprotective than Gurigumu-7. The results suggested that MF is a promising bioactive fraction for the development of new hepatoprotective medicine with better formulation and quality control properties.

[Clinical features of childhood purulent meningitis caused by Escherichia coli and Streptococcus pneumoniae: a comparative analysis].

OBJECTIVE: To investigate the differences in clinical features of childhood purulent meningitis (PM) caused by Escherichia coli and Streptococcus pneumoniae, and to provide help for the selection of antibiotics for PM children with unknown etiology. METHODS: A retrospective analysis was performed for the clinical data of children with PM caused by Escherichia coli (12 children) or Streptococcus pneumoniae (15 children). RESULTS: Compared with the Streptococcus pneumoniae infection group, the Escherichia coli infection group had a significantly higher proportion of children with an age of onset of <3 months and a significantly higher incidence rate of convulsion, but significantly lower incidence rates of severe fever (>39°C) and disturbance of consciousness and a significantly lower proportion of children with an increased leukocyte count at diagnosis (>12×10(9)/L). The results of routine cerebrospinal fluid test and biochemical examinations showed no significant differences between the two groups. Escherichia coli and Streptococcus pneumoniae were resistant to cephalosporins and had a sensitivity to chloramphenicol more than 90%. Escherichia coli was fully sensitive to meropenem and Streptococcus pneumoniae was fully sensitive to vancomycin. CONCLUSIONS: PM caused by Escherichia coli and Streptococcus pneumoniae has different clinical features. As for PM children with severe fever, disturbance of consciousness, and an increased leukocyte count, the probability of Streptococcus pneumoniae infection should be considered. For PM children with an age of onset of <3 months, medium- and low-grade fever, frequent convulsions, and a leukocyte count of <12×10(9)/L, the probability of Escherichia coli infection should be considered.

Are afebrile seizures associated with minor infections a single seizure category? A hospital-based prospective cohort study on outcomes of first afebrile seizure in early childhood.

OBJECTIVE: To explore if afebrile seizures associated with minor infections are a single category of seizure, or a set of different kinds of seizures. METHODS: We conducted this prospective cohort study on three kinds of first afebrile seizure: first afebrile seizure associated with gastrointestinal infection (AS-GI), first afebrile seizure associated with nongastrointestinal infection (AS-nGI), and first unprovoked seizure (US). The Kaplan-Meier estimate risks of recurrent seizures were analyzed and compared pairwise. The characteristics of recurrent seizures were also compared pairwise. RESULTS: The Kaplan-Meier estimate risks of recurrent seizure at 2 years of the AS-GI, AS-nGI, and US groups were 6.9%, 23.7%, and 37.8%, respectively. The pairwise differences were significant between the AS-GI and US groups (p < 0.001) and between the AS-GI and AS-nGI groups (p = 0.001), but not significant between the US and AS-nGI groups (p = 0.066). Among unprovoked subsequent seizures in patients with recurrence, the pairwise differences were significant between the AS-GI and US groups (p < 0.001) and between the AS-GI and AS-nGI groups (p = 0.005), but not significant between the US and AS-nGI groups (p = 0.417). SIGNIFICANCE: Afebrile seizures associated with minor infections are indeed of two distinguishable kinds: AS-GI, if free of risk factors such as a family history of epilepsy, had a better prognosis and should be categorized as an acute symptomatic seizure, whereas patients with first AS-nGI, like patients with first US, may have recurrent unprovoked seizures, which suggests this category's essential difference from AS-GI.

A peptide from the Japanese encephalitis virus failed to induce the production of anti-N-methyl-d-aspartate receptor antibodies via molecular mimicry in mice.

Background: The development of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis following viral encephalitis, such as Japanese encephalitis, has received increasing attention in recent years. However, the mechanism of anti-NMDAR antibody production following Japanese encephalitis has not been explored. Methods: A peptide from the Japanese encephalitis virus (JEV), which shares a similar amino acid sequence with GluN1, was identified by sequence comparison. We then explored whether active subcutaneous immunization with the JEV peptide could induce the production of anti-NMDAR antibodies and related pathophysiological and behavioral changes in mice. In addition, a published active immune model of anti-NMDAR encephalitis using a GluN1 peptide was used as the positive control. Results: A 6-amino-acid sequence with 83 % similarity between the envelope protein of the JEV (HGTVVI) and GluN1 (NGTHVI) was identified, and the sequence included the N368/G369 region. Active immunization with the JEV peptide induced a substantial and specific immune response in mice. However, anti-NMDAR antibodies were not detected in the serum of mice immunized with the JEV peptide by ELISA, CBA, and TBA. Moreover, mice immunized with the JEV peptide presented no abnormities related to anti-NMDAR antibodies according to western blotting, patch clamp, and a series of behavioral tests. In addition, active immunization with a recently reported GluN1 peptide failed to induce anti-NMDAR antibody production in mice. Conclusions: In this study, the attempt of active immunization with the JEV peptide to induce the production of anti-NMDAR antibodies via molecular mimicry failed. The pathogenesis of anti-NMDAR encephalitis following Japanese encephalitis remains to be elucidated.

Effects of the gut microbiota and its metabolite short-chain fatty acids on endometriosis.

In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis.

Pediatric myasthenia gravis with a combination of AChR and RyR is associated with an earlier onset and lower CSR rate: A cohort study in southwest China.

BACKGROUND: The clinical manifestations and prognosis of myasthenia gravis are related to antibodies, and children are affected differently than adults. The presence of ryanodine receptor and titin antibodies in adults indicates late onset and severe disease related to thymoma, but their role in children is rarely reported. METHODS: This study collected a cohort of children according to inclusion and exclusion criteria, consisting of antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The differences among groups in general conditions, clinical manifestation, treatment and prognosis were compared. RESULTS: In total, 171 patients were included: 33 patients (19.30%) were antibody-negative, 84 patients (49.12%) were positve for AChR antibody, 22 patients (12.87%) were positve for AChR and RyR antibodies, 5 patients (2.92%) were positve for AChR and Titin antibodies, and 27 patients (15.79%) were positve for AChR, RyR and Titin antibodies. The median onset age of all the patients was 57.8 (9-177) months, and patients with AChR and RyR antibodies (p = 0.02) and AChR, RyR and Titin antibodies (p = 0.0006) had a younger onset age than patients with AChR antibodies. The rate of generalized MG and MG-ADL before treatment in the AChR-, RyR- and Titin antibody-positive groups was distinctly higher than that in the AChR antibody-positive group (p = 0.038, p = 0.0325). The rate of IVIG use in the AChR-, RyR- and Titin antibody-positive groups (p = 0.0388) was higher than that in the AChR antibody-positive group. The rate of immunosuppressant use in the AChR and RyR antibody-positive group (p = 0.0415) and in the AChR, RyR and Titin antibody-positive group (p = 0.0006) was higher than that in the AChR antibody-positive group. Plasmapheresis was performed in 1 case in the AChR-, RyR- and Titin antibody-positive groups. The CSR rate in the AChR and RyR antibody-positive group (p = 0.0423) and in the AChR, RyR and Titin antibody-positive group (p = 0.0152) was significantly lower than that in the AChR antibody-positive group. Gender, ptosis severity, and CSR time were not significantly different between groups. CONCLUSIONS: We summarized one of the largest cohorts of pediatric MG patients and compared the clinical phenotype of patients with antibody-negative, AChR-positive, and AChR with or without titin and RyR antibodies. The results showed that patients with AChR and RyR antibodies had a younger onset age, a higher immunosuppressant use rate and a lower CSR rate.

Vaccination against COVID-19 and potential protective effects on seizure recurrence in children with epilepsy: A cross-sectional survey.

OBJECTIVE: Despite strong evidence on the safety and tolerability of the COVID-19 vaccine, data on vaccination in children with epilepsy, particular younger children with specific epilepsy syndromes, are limited. The protective effects of vaccination against seizure increase upon COVID-19 infection also remain to be elucidated. METHODS: Questionnaire surveys were distributed online via an established WeChat group for patient management as well as in our outpatient clinic. The data collected included demographics and clinical information related to COVID-19 vaccination and infection. Detailed information related to epilepsy diagnosis and treatment was also collected from our patient database. Logistic regression analysis was performed to determine the factors associated with non-vaccination. The characteristics of seizures following COVID-19 infection were described. RESULTS: In total, 354 suitable questionnaires were included in the study. The median age at survey was 6 years (interquartile range 4, 9). The most common epilepsy syndrome was self-limited epilepsy (n = 153, 43.2%), followed by developmental and/or epileptic encephalopathy (D/EE, n = 81, 22.9%) and genetic generalized epilepsy (n = 59, 16.7%). The vaccine uptake rate was 43.8% (n = 155), and all related side-effects (n = 11, 7.1%) remitted spontaneously. Younger age (odds ratio [OR] = 0.877, P = 0.001), D/EE (OR = 5.096, P = 0.008), and less than six months seizure-freedom before vaccination (OR = 3.026, P = 0.005) were associated with unwillingness to be vaccinated. There were no significant differences in the rate of COVID-19 infection (33.7% vs 32.7%, P = 0.879) and resultant increased seizure activity following infection between the vaccinated and unvaccinated groups after propensity score matching (9.1% vs 15.6%, P = 0.428).Three unvaccinated cases of Dravet syndrome developed status epilepticus following COVID-19 infection. SIGNIFICANCE: Vaccination against COVID-19 is safe and well tolerated in children, even in younger patients with D/EE. Although the risk of worsening seizures following COVID-19 infection may not be reduced by immunization, education focused on increased vaccination in pediatric epilepsy is still warranted.

Clinical characteristics of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children: A case series of 16 patients.

PURPOSE: To investigate the clinical characteristics of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. METHODS: We reviewed the medical records of Children's Hospital of Chongqing Medical University from January 2020 to September 2021 and retrospectively analysed the clinical features, magnetic resonance imaging (MRI) findings, laboratory findings, treatment and outcome of children with autoimmune GFAP astrocytopathy. RESULTS: Sixteen patients were included: 6 and 10 tested positive for GFAP-IgG in cerebrospinal fluid (CSF) and both CSF and serum, respectively. The median patient age was 115 months (range: 36-180 months), and 7 patients (43.8%) were male. All patients had the clinical syndrome of encephalitis/meningoencephalitis with or without myelitis: encephalitis (8), meningoencephalitis (3), encephalomyelitis (1) and meningoencephalomyelitis (4). The most common clinical symptoms were fever (11), altered consciousness (11), headache (10) and seizure (9). Four patients developed central respiratory failure for which mechanical ventilation was needed. All patients showed hyperintense T2-weighted lesions on brain MRI in the cerebral white matter (13), brainstem (11), basal ganglia (11), thalamus (9), and cerebellum (3). Nine patients (56%) had abnormal hyperintense lesions in the bilateral basal ganglia and thalamus. Six of 12 patients who underwent gadolinium-enhanced brain MRI showed abnormal enhancement images, and five of them showed linear perivascular radial enhancement. The modified Rankin scale (mRS) score decreased significantly in most patients after immunotherapy. Two patients with coexisting neural autoantibodies relapsed; however, 15 patients who were followed up successfully had favorable outcomes at the last follow-up. CONCLUSION: Children with autoimmune GFAP astrocytopathy usually have a clinical syndrome of encephalitis/meningoencephalitis with or without myelitis. Except for the linear perivascular radial gadolinium enhancement pattern, hyperintense lesions in the bilateral basal ganglia and thalamus might be another characteristic brain MRI finding of autoimmune GFAP astrocytopathy in children. Although a few patients with coexisting neural autoantibodies might relapse, children with autoimmune GFAP astrocytopathy usually have favorable outcomes after immunotherapy.

Clinical, radiological, therapeutic and prognostic differences between MOG-seropositive and MOG-seronegative pediatric acute disseminated encephalomyelitis patients: a retrospective cohort study.

Objective: This study aimed to compare the clinical, radiological, therapeutic, and prognostic differences between pediatric patients showing acute disseminated encephalomyelitis (ADEM) with and without myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: We retrospectively collected all available data of children diagnosed with ADEM and tested for serum MOG antibodies at the Children's Hospital of Chongqing Medical University from January 2017 to May 2021. Results: A total of 62 patients were included in our cohort, of which 35 were MOG-seropositive and 27 were MOG-seronegative. MOG-seropositive ADEM children presented with significantly lower rates of seizures (P = 0.038) and cranial nerve (III-XII) palsy (P = 0.003). Isolated leukocytosis in the blood was more common in ADEM children with MOG antibodies (P < 0.001). The two groups showed no significant differences in the distributions and extent of the MRI lesions as well as the appearance of typical/atypical magnetic resonance imaging (MRI) features. MOG-seropositive children were more likely to relapse (P = 0.017) despite having slower oral prednisolone tapering after acute treatments (P = 0.028). In scoring performed on the basis of two neurological function scoring systems, MOG-seropositive children showed milder neurological disability status at onset (P = 0.017 and 0.025, respectively) but showed no difference during follow-up. Conclusion: In summary, the differences in the clinical manifestations and auxiliary examination findings for MOG-seropositive and MOG-seronegative ADEM children lacked significance and specificity, making early identification difficult. MOG-seropositive children were more likely to relapse and showed slower steroid tapering. Moreover, MOG-seronegative children tended to have more severe neurological impairments at onset with no difference during follow-up.