Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

[Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis]. / å„¿ç«¥çœ¼è‚Œåž‹é‡ç—‡è‚Œæ— åŠ›ä¸åŒå ç–«æŠ‘åˆ¶å‰‚æ²»ç–—æ–¹æ¡ˆçš„å›žé¡¾æ€§åˆ†æž.

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS: For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

[Early identification and diagnosis of epilepsy related to fever sensitivity].

Febrile seizures are the most common nervous system disease in childhood, and most children have a good prognosis. However, some epilepsy cases are easily induced by fever and are characterized by "fever sensitivity", and it is difficult to differentiate such cases from febrile seizures. Epilepsy related to fever sensitivity includes hereditary epilepsy with febrile seizures plus, Dravet syndrome, and PCDH19 gene-related epilepsy. This article mainly describes the clinical manifestations of these three types of epilepsy and summarizes their clinical features in the early stage of disease onset, so as to achieve early identification, early diagnosis, and early intervention to improve prognosis.

Detection and diagnostic value of serum NSE and S100B protein levels in patients with seizures associated with mild gastroenteritis: A retrospective observational study.

Benign convulsions with mild gastroenteritis (CwG) and febrile seizures (FS) associated with mild gastroenteritis are 2 different diseases in the spectrum of seizures associated with mild gastroenteritis. However, specific and useful indicators for the identification of the 2 diseases are lacking. A retrospective analysis was performed to compare the serum neuronal-specific enolase (NSE) and S100B protein levels between patients with these 2 diseases to evaluate the value of NSE and S100B for differential diagnosis between these 2 diseases.The clinical data and NSE and S100B protein levels of 81 children with seizure-associated mild gastroenteritis were collected. According to the axillary temperature at the time of convulsions, all patients were classified into an afebrile seizure (AFS) group, hereafter called the CwG group (n = 46), and a febrile seizure group (FS group, n = 35).The serum NSE level was higher in the CwG group than in the FS group (14.046 (11.095, 19.266) pg/ml and 9.034 (7.158, 12.165) pg/ml, respectively, P < .001); however, the serum S100B protein levels in the CwG and the FS group were not significantly different (P > .05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for NSE was 0.806, P = .000, which was statistically significant. The Youden index was largest (0.605) for a serum NSE cut-off value of 10.460 pg/ml, which yielded a sensitivity and specificity of 89% and 71%, respectively, for prediction of a CwG diagnosis.NSE may contribute to the differential diagnosis of CwG and FS associated with mild gastroenteritis.

Clinical features of campylobacter-associated benign convulsions with mild gastroenteritis compared with rotavirus convulsions.

PURPOSE: The aim of the present study was to compare the clinical features of campylobacter-associated benign convulsions with mild gastroenteritis (BCWG) with rotavirus-associated BCWG in China. METHODS: The medical records of BCWG patients admitted to Children's Hospital of Jiangxi Province in China between January 2015 and January 2017 were reviewed in this retrospective study. RESULTS: Ultimately, 318 patients were diagnosed with BCWG. Two hundred and two cases were tested for Campylobacter jejuni antigen, and seven (3.47%) were positive. A total of 248 cases were tested for rotavirus antigen, and 44 (17.74%) were positive. Campylobacter-associated BCWG occurred in summer and autumn. In contrast, rotavirus-associated BCWG mainly occurred in winter. In the campylobacter-associated BCWG group, five patients (71.43%) had two or more seizures. In one patient(14.29%), the seizure occurred on the first day of gastroenteritis; three patients (42.86%) had seizures on the second day, and three (42.86%) had seizures on the third day or later. Thirteen seizures were observed in the campylobacter-associated BCWG group; of these, 11 (84.62%) lasted less than 5 min, and 11 (84.62%) were generalized seizures. Phenobarbital (5 mg/kg/time) was effective in all 6 cases (100%) in which it was used. Other than the different seasonal distributions, the clinical features of campylobacter-associated BCWG and rotavirus-associated BCWG may be similar. CONCLUSIONS: Campylobacter is one of the pathogens responsible for BCWG, especially in summer and autumn. Other than the different seasonal distributions, the clinical features of campylobacter-associated BCWG and rotavirus-associated BCWG may be similar.

Clinical characteristics and etiology of bacterial meningitis in Chinese children >28 days of age, January 2014-December 2016: A multicenter retrospective study.

OBJECTIVE: To explore the clinical characteristics and etiology of bacterial meningitis (BM) in Chinese children. METHOD: BM cases in children 28days to 18 years old were collected from January 2014-December 2016 and screened according to World Health Organization standards. Clinical features, pathogens, and resistance patterns were analyzed. RESULTS: Overall, 837 cases were classified into five age groups: 28 days-2 months (17.0%), 3-11 months (27.8%), 12-35 months (24.0%), 3-6 years (13.9%), and >6years (17.3%). Major pathogens were Streptococcus pneumoniae (S. pneumoniae, n=136, 46.9%), group B Streptococcus (GBS, n=29, 10.0%), and Escherichia coli (E. coli, n=23, 7.9%). In infants <3 months old, GBS (46.5%) and E. coli (23.3%) were most common; in children >3 months old, S. pneumoniae (54.7%), which had a penicillin non-susceptibility rate of 55.4% (36/65), was most frequent. The resistance rates of S. pneumoniae and E. coli to cefotaxime and ceftriaxone were 14.0%/40.0% and 11.3%/68.4%, respectively. All GBS isolates were sensitive to penicillin. CONCLUSIONS: The occurrence of BM peaked in the first year of life, while S. pneumoniae was the predominant pathogen in children >3months of old. The antibiotic resistance of S. pneumoniae was a concern.

[Immunological mechanism of prednisone in the treatment of infantile spasm].

OBJECTIVE: To investigate the immunological mechanism of prednisone in the treatment of infantile spasm (IS) by evaluating the immune function of IS children before and after treatment. METHODS: Thirty children with IS were enrolled as IS group. Thirty healthy infants who underwent physical examination were enrolled as healthy control group. Fasting venous blood was collected for both groups before and after prednisone treatment. Chemiluminescence was used to measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Immunoturbidimetric assay was used to measure serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow cytometry was used to measure the percentages of T lymphocyte subsets (CD3+, CD4+, and CD8+). The clinical outcome and electroencephalographic findings were evaluated for all IS children after prednisone treatment. RESULTS: The IS group had significantly higher serum levels of IL-2R, IL-8, and TNF-α than the healthy control group before treatment (P<0.05). The mean number of daily ictal clusters was positively correlated with the levels of IL-2R, IL-8, and TNF-α in IS children, the mean number of total daily seizures was positively correlated with IL-8 level, and any two indices out of IL-2R, IL-8, and TNF-α were positively correlated with each other (P<0.05). Among the 30 IS children treated with prednisone, 19 achieved seizure control; electroencephalography showed that 18 children achieved complete remission of hyperarrhythmia. After treatment, the IS group had significant reductions in the numbers of daily ictal clusters and total daily seizures, significant improvement in developmental quotient (P<0.05), and significant reductions in serum levels of IL-2R, L-8, and TNF-α, the percentage of CD4+ T lymphocytes, and CD4+/CD8+ ratio (P<0.05), as well as a significant increase in the percentage of CD8+ T lymphocytes (P<0.05). CONCLUSIONS: IS children have immune dysfunction. Prednisone can control seizures in IS children, possibly by regulating and improving immune dysfunction.

Efficacy and tolerability of high-dose prednisone in Chinese children with infantile spasms.

OBJECTIVES: The aim of this study is to preliminarily evaluate the clinical efficacy and safety of high-dose prednisone in the treatment of infantile spasms (IS) in China, and to provide additional choice of the therapy of IS. METHODS: Twenty patients aged 3-53 months with IS were collected in the Department of Neurology of Jiangxi Children's Hospital from May in 2011 to December in 2012, who were placed on high-dose prednisone (took prednisone tablet of 10mg four times a day) for 2 weeks during admission to our hospital. The assessment of spasms seizure and video-EEG monitoring were preformed before treatment and after 2 weeks and the end of treatment of the regimen (7 weeks), respectively. All of the children were followed-up for 2-14 months. RESULTS: Among 20 cases, there were 16 cases (80.0%) with complete cessation of spasms after 2 weeks and 13 cases (65.0%) after 7 weeks. There were 19 cases with typical or modified hypsarrhythmia in 20 cases. No matter after 2 or 7 weeks, there were 12 cases showed complete resolution of hypsarrhythmia and 7 cases with only a partial remission of hypsarrhythmia. After a follow-up of 2-14 months, the longest spasm-free interval was 14 months and the shortest one was 11 days. Six cases relapsed in different periods, and the relapse rate was 35.3%. Amongst the main adverse events, there were Cushing's symptoms in 15 cases (75.0%), irritability in 8 cases (40.0%), drosiness in 3 cases (15.0%), high blood pressure in 3 cases (15.0%), and infections in 8 cases (40.0%), but no one stopped the treatment because of the adverse reactions. CONCLUSION: In total, high-dose prednisone was effective and well-tolerated in children with IS in China. Maybe the regimen will become a new choice in the treatment of IS.

Febrile seizure recurrence reduced by intermittent oral levetiracetam.

OBJECTIVE: Febrile seizure (FS) is the most common form of childhood seizure disorders. FS is perhaps one of the most frequent causes of admittance to pediatric emergency wards worldwide. We aimed to identify a new, safe, and effective therapy for preventing FS recurrence. METHODS: A total of 115 children with a history of two or more episodes of FS were randomly assigned to levetiracetam (LEV) and control (LEV/control ratio = 2:1) groups. At the onset of fever, LEV group was orally administered with a dose of 15-30 mg/kg per day twice daily for 1 week. Thereafter, the dosage was gradually reduced until totally discontinued in the second week. The primary efficacy variable was seizure frequency associated with febrile events and FS recurrence rate (RR) during 48-week follow-up. The second outcome was the cost effectiveness of the two groups. RESULTS: The intention-to-treat analysis showed that 78 children in LEV group experienced 148 febrile episodes. Among these 78 children, 11 experienced 15 FS recurrences. In control group, 37 children experienced 64 febrile episodes; among these 37 children, 19 experienced 32 FS recurrences. A significant difference was observed between two groups in FS RR and FS recurrence/fever episode. The cost of LEV group for the prevention of FS recurrence is lower than control group. During 48-week follow-up period, one patient in LEV group exhibited severe drowsiness. No other side effects were observed in the same patient and in other children. INTERPRETATION: Intermittent oral LEV can effectively prevent FS recurrence and reduce wastage of medical resources.

[Management of anti-N-methyl-D-aspartate receptor encephalitis in children].

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a new category of severe, potentially treatable autoimmune encephalitis and can appear in patients of all ages, but more frequently in children. It is a highly characteristic syndrome evolving in five stages: the prodromal phase (viral infection-like symptoms), psychotic phase, unresponsive phase, hyperkinetic phase, and gradual recovery phase. The treatment for this disorder includes first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumor removal. Hereby the progresses, selections and shortcomings of the treatment protocols for this disease are introduced.

[Hair root fragile X mental retardation protein assay for the diagnosis of fragile X syndrome].

OBJECTIVE: Fragile X syndrome (FXS) may be identified by many methods, such as PCR assay and Southern blot. However, each method has its limits or shortcomings. This study explored the reliability of the rapid, convenient and inexpensive hair root fragile X mental retardation protein (FMRP ) assay in the identification of FXS. METHODS: FMRP in hair roots was determined by immunohistochemistry assay in 80 healthy children, in 40 children with mental retardation of unknown etiology and in 12 family members in one pedigree of FXS. FXS was confirmed by 7-deza-dGTP PCR. RESULTS: There was a high expression of FMRP in hair roots (> or =80%) in healthy children. Two children were confirmed with FXS by 7-deza-dGTP PCR in 40 children with mental retardation of unknown etiology. FMRP expression was 10% and zero respectively in the two children. The other 38 children had FMRP expression of more than 80%. FMRP was not expressed in the two cases of FXS from the pedigree of FXS. CONCLUSIONS: Inexpensive, rapid and convenient hair root FMRP assay is reliable for the diagnosis of FXS and may be widely applied for screening and diagnosing FXS in children with mental retardation.