Efficacy and safety of phenobarbital for benign convulsions with mild gastroenteritis: A prospective randomized controlled study.

BACKGROUND: previous studies have shown that phenobarbital (PB) is a effective and safe drug in the treatment of benign convulsions with mild gastroenteritis (CwG), but there is a lack of large sample prospective randomized controlled study of different doses. This study was a prospective randomized controlled study on the efficacy and safety of different doses of phenobarbital for CwG. There has been no similar study. METHODS: One hundred twenty CwG cases were included in this study. All of them were hospitalized in the Department of Neurology of Jiangxi Provincial Children's Hospital from January 2019 to August 2021. They were randomly divided into 10 mg/kg single dose group (Group A, n = 60) and 5 mg/kg single dose group (Group B, n = 60). The criteria for judging the efficacy of PB in our study were there was no convulsion in the course of acute gastroenteritis within 2 weeks after using PB. RESULTS: The effective rate was 93.33% in group A and 80.00% in group B. There was significant difference between the 2 groups (P < .05). Drowsiness was the most frequent adverse reaction. 14 cases in group A and 7 cases in group B had drowsiness. There was no significant difference between the 2 groups in the incidence of adverse events such as somnolence, ataxia, abnormal liver function, anemia, abnormal leukocyte, respiratory depression, cognitive impairment, rash, abnormal platelet and abnormal renal function (P > .05). All side reaction were transient. CONCLUSION: it is suggested that PB 10 mg/kg intravenously should be used as soon as possible for CwG, which has high effectiveness and safety.

Case report of two affected siblings in a family with thiamine metabolism dysfunction syndrome 5: a rare, but treatable neurodegenerative disease.

BACKGROUND: Thiamine metabolism dysfunction syndrome 5 (THMD5) is a rare inherited metabolic disorder due to thiamine pyrophosphokinase 1(TPK1) deficiency, caused by mutations in TPK1. The core symptoms of the disease is acute or subacute onset encephalopathy, ataxia, muscle hypotonia, and regression of developmental milestones in early infancy, repeatedly triggered by acute infectious illness. However, we report two brothers of THMD5 with compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn), but the prognosis is quite different if thiamine suppled. According to our current knowledge, the missense variant c.224 T > A p.(Ile75Asn) was not published previously. CASE PRESENTATION: Here, we describe two affected siblings in a Chinese family, after an uneventful pregnancy to non-consanguineous and healthy parents. The older brother presented with normal development during the first 6 months of life, but developed regression of developmental milestones after, accompanied with muscle hypotonia, and chronic encephalopathy, and died at 1 year and 6 months old. The younger brother presented with acute onset encephalopathy, ataxia, muscle hypotonia, repeatedly triggered by acute infectious illness. He was compound heterozygous for the mutations c.614-1G > A,c.224 T > A p.(Ile75Asn) identified by whole exome sequencing. He was diagnosed of THMD5 when he was 11 month. Oral supplementation of thiamine 100 mg/day, the symptoms gradually disappeared. At the age of 2 years and 4 months, he stoped thiamine, his symptoms returned and were once again relieved by oral supplementation of thiamine 100 mg/day. CONCLUSIONS: THMD5 is a rare, but treatable neurodegenerative disease, the clinical phenotype ranges from mild to severe. Massive-dose of thiamine supplementation may ameliorate the course of TPK1 deficiency. When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis. Treatment with thiamine while awaiting the outcome of diagnostic tests may be a good choice.

A case report of atypical hemiplegic migraine with nonheadache onset in a Chinese child.

BACKGROUND: Hemiplegic migraine (HM) is an uncommon subtype of migraine with aura including motor weakness. The core symptoms of HM are headache and motor weakness. However, we report a rare case of atypical HM with nonheadache onset in a Chinese child who was misdiagnosed several times. CASE PRESENTATION: We report a Chinese boy whose onset was sudden when he was 3 years old. He presented with a variety of phenotypes, including fever, vomiting, alternating hemiplegia, and drowsiness, but no headache in the initial stages. Magnetic resonance imaging (MRI) demonstrated unilateral cerebral oedema during the initial episode of hemiplegia. These symptoms recurred many times. As the disease progressed, the patient developed episodic headache. The patient was misdiagnosed several times with encephalitis, alternating hemiplegia of childhood (AHC) and mitochondrial encephalopathy. Whole-exome next-generation sequencing revealed a de novo heterozygous missense mutation in the ATP1A2 gene(p.Gly715Arg) classified as pathogenic and eventually led to a diagnosis of HM when he was 11 years old. Flunarizine was subsequently administered, and no recurrence was found during follow-up. CONCLUSIONS: HM in children may be atypical in the initial stage of the disease, which could manifest as fever, alternating hemiplegia and drowsiness but no headache at the onset. This could easily lead to misdiagnosis. With age, it may eventually manifest as typical HM. Therefore, attention should be given to differentiation in clinical practice.When similar clinical cases appear, gene detection is particularly important, which is conducive to early diagnosis and treatment.

Balamuthia mandrillaris encephalitis in a child: case report and literature review.

Balamuthia mandrillaris encephalitis is a rare disease with high mortality in the children. Due to the lack of specificity in clinical manifestations, laboratory tests, and neuroimaging, the diagnosis of the disease is difficult, especially the diagnosis of etiology. Currently, the evidence shows that the diagnosis of the disease depends on local brain biopsy or autopsy, and it is difficult to detect the pathogens by traditional etiological detection methods in blood and cerebrospinal fluid. We report a 9-year-old Chinese girl with B. mandrillaris encephalitis who was diagnosed with metagenomic next-generation sequencing (mNGS). The technology of mNGS can provide rapid, early etiological diagnosis without the need for a local brain biopsy, which can buy time for the early treatment of patients. We also provide a comprehensive literature review on this disease.

High-dose prednisone therapy for infantile spasms and late-onset epileptic spasms in China: The addition of topiramate provides no benefit.

PURPOSE: To compare the clinical efficacy of high-dose prednisone monotherapy and the combination of hormone and moderate-dose topiramate (TPM) therapy in children with infantile spasms (IS) and late-onset epileptic spasms (ES), and to evaluate whether the addition of TPM would provide more benefits for patients. METHODS: All patients were assigned to receive either high-dose prednisone alone (the maximum doses was 60 mg a day) or high-dose prednisone with TPM (the moderate doses was 5 mg/kg/day). The primary outcome was the proportion of children who achieved cessation of spasms at day-49 or day-56 after initial treatment (the minimum duration of treatment were 49 days). RESULTS: 77 patients were randomly divided into two groups. The control rate of spasms on day-14 in hormone monotherapy was similar to combination therapy (71.8% vs 76.3%, p = 0.796). The cessation of spasms rate of patients on day-49 or day-56 was also similar between the two groups (71.8% vs 65.8%, p = 0.569). After 4 months, the cessation of spasms rate of patients in the group of hormone monotherapy was higher than the group of combination therapy, but there was no significant difference (61.5% vs 50.0%, p = 0.308). CONCLUSION: The efficacy of the combination therapy was not better than that of the monotherapy in achieving spasm freedom at 14-days, 49-days or 56-days and day-120 in the patients. Adding-on moderate-dose TPM did not help more children achieve spasm freedom and provided no benefit for prevention of IS and late-onset ES in short term. Higher-dose regimens of TPM might be more effective.

Clinical and molecular genetic characterization of familial MECP2 duplication syndrome in a Chinese family.

BACKGROUND: Chromosomal duplication at the Xq28 region including the MECP2 gene, share consistent clinical phenotypes and a distinct facial phenotype known as MECP2 duplication syndrome. The typical clinical features include infantile hypotonia , mild dysmorphic features, a broad range of neurodevelopmental disorders, recurrent infections, and progressive spasticity. METHODS: This Chinese MECP2 duplication syndrome family includes six patients (five males and one female), and four asymptomatic female carriers. Two kinds of chips including 4x180K CNV + SNP chip and custom 8x60K CNV chip were used to detect MECP2 duplication, and then fluorescent in situ hybridization (FISH) analysis was performed to identify the exact copy number of MECP2. X-chromosome inactivation (XCI) analysis on AR gene was detected for all female family members, and the m icrosatellite analysis on MECP2 was used to validate the recombination event on MECP2 region. RESULTS: The affected male subjects presented with a broad range of neurodevelopmental symptoms (severe intellectual disability, developmental delay, seizure, language deficit, and autism spectrum disorder) as well as facial dysmorphism and other symptoms which were consistent with that of Western patients previous reported. Seizure is reported in Chinese patients for the first time. In addition, we validated three recombination events for the MECP2-duplication allele during maternal transmission due to X homologous recombination. CONCLUSIONS: We provided the largest known Chinese pedigree with MECP2 duplication syndrome. The detailed clinical description and molecular genetic characterization in all affected family members further delineate the typical phenotype of this genomic disorder in Chinese population.

[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.