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.

c.3G>A mutation in the CRYAB gene that causes fatal infantile hypertonic myofibrillar myopathy in the Chinese population.

Infantile hypertonic myofibrillar myopathy is characterized by the rapid development of rigid muscles and respiratory insufficiency soon after birth, with very high mortality. It is extremely rare, and only a few cases having been reported until now. Here we report four Chinese infants with fatal neuromuscular disorders characterized by abdominal and trunk skeletal muscle stiffness and rapid respiratory insufficiency progression. Electromyograms showed increased insertion activities and profuse fibrillation potentials with complex repetitive discharges. Immunohistochemistry staining of muscle biopsies showed accumulations of desmin in the myocytes. Powdery Z-bands with dense granules across sarcomeres were observed in muscle fibers using electron microscopy. All patients carry a homozygous c.3G>A mutation in the CRYAB gene, which resulted in the loss of the initiating methionine and the absence of protein. This study's findings help further understand the disease and highlight a founder mutation in the Chinese population.

[Clinical features of children with lysinuric protein intolerance and SLC7A7 gene mutation: an analysis of 3 cases].

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10 mL/day) and vitamin D (400 IU/day). In addition, patient 3 was given prednisone acetate (5 mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.

[Brain injury after induction chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI. METHODS: The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively. RESULTS: Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy. CONCLUSIONS: The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.

[Alterations of CD4+CXCR5+Tfh cells and its transcription regulatory factors in children with asthma].

OBJECTIVE: To study the alterations of follicular T helper cells (CD4(+)CXCR5(+)Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA. METHODS: Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4(+)CXCR5(+)Tfh cells on CD4(+)T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double -antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21. RESULTS: The proportion of CD4(+)CXCR5(+)Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4(+)CXCR5(+)Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05). CONCLUSIONS: The abnormal proportion of CD4(+)CXCR5(+)Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4(+)CXCR5(+)Tfh cells in children with acute asthma.

Association of LONP1 gene with epilepsy and the sub-regional effect.

The LONP1 gene encodes Lon protease, which is responsible for degrading damaged or misfolded proteins and binding mitochondrial DNA. Previously, LONP1 variants have been identified in patients with cerebral, ocular, dental, auricular, and skeletal anomalies (CODAS syndrome) and mitochondrial diseases. Seizures were occasionally observed. However, the association between LONP1 and epilepsy remains elusive. In this study, we performed trio-based whole-exome sequencing in a cohort of 450 patients with unexplained epilepsy and identified four pairs of compound heterozygous LONP1 variants in four unrelated cases. All patients exhibited good responses to anti-seizure medications and demonstrated no developmental delay or intellectual disabilities. The variant allele frequencies observed in this study were absent or low in the general population and were significantly lower than those of benign variants. At least one variant in each biallelic pair affected hydrogen bonding and/or altered protein stability. The CODAS syndrome-associated variants were concentrated in the AAA+ module, especially the α domain. Four of the five mitochondrial disease-associated variants were located in the AAA + domain and the NTD5H and NTD3H subdomains. In contrast, each of the biallelic variants from the patients with pure epilepsy had one variant located in the linker domain, and the other variant located in the mitochondrial targeting sequence or P domain. This study suggested that LONP1 gene is potentially a novel candidate gene for pure epilepsy. The phenotypic variation is associated with the sub-regional effects of variants.

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.

[Analysis of clinical features and GCDH gene mutations in four patients with glutaric academia type I].

OBJECTIVE: To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations. METHODS: The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing. RESULTS: All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered. CONCLUSION: Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.

[Utilization of high-resolution melting analysis to screen patients with neonatal intrahepatic cholestasis caused by citrin deficiency].

OBJECTIVE: To assess the feasibility of high-resolution melting (HRM) analysis for screening patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). METHODS: Based on previous studies on SLC25A13 gene in Chinese patients with NICCD, four hotspot mutations (851del4, 1638ins23, IVS6+5G>A and IVS16ins3kb) were selected. Results of the HRM analysis was validated using 50 negative controls and 20 patients with NICCD whose genotypes were confirmed previously by direct sequencing. With the established protocol, 171 suspected patients were enrolled. Samples with abnormal melting curves were further validated by DNA sequencing. RESULTS: HRM analysis can accurately determine the genotypes of all negative controls and patients. The sensitivity and specificity of the technique reached 100% (70/70). The melting curves of samples with the same genotype were highly reproducible. In 171 suspected patients, seven NICCD patients were detected by HRM. Identified mutations have included one case of 851del4 homozygote, one case of IVS6+5G>A heterozygote, 3 cases of 851del4 heterozygotes, one case of [IVS6+5G>A]+[ 851del4] and one case of [1638ins23+IVS16ins3kb]+[1638ins23]. All mutations were subsequently confirmed by DNA sequencing. CONCLUSION: HRM analysis is a convenient, high-throughput and rapid technique for the screening of NICCD patients.

Liver transplantation for late-onset ornithine transcarbamylase deficiency: A case report.

BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disorder and characterized by marked elevation of blood ammonia. The goal of treatment is to minimize the neurological damage caused by hyperammonemia. OTCD can be cured by liver transplantation (LT). Post-transplant patients can discontinue anti- hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia. The neurological damage caused by hyperammonemia is almost irreversible. CASE SUMMARY: An 11.7-year-old boy presented with headache, vomiting, and altered consciousness. The patient was diagnosed with late-onset OTCD. After nitrogen scavenging treatment and a protein-free diet, ammonia levels were reduced to normal on the third day of admission. Nevertheless, the patient remained in a moderate coma. After discussion, LT was performed. Following LT, the patient's blood ammonia and biochemical indicators stabilized in the normal range, he regained consciousness, and his nervous system function significantly recovered. Two months after LT, blood amino acids and urine organic acids were normal, and brain magnetic resonance imaging showed a decrease in subcortical lesions. CONCLUSION: LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy, and LT can be actively considered when early drug therapy is ineffective.

Protist.guru: A Comparative Transcriptomics Database for Protists.

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still largely neglected. To address this gap, we used gene expression data from 17 protist species to create protist.guru: an online database equipped with tools for identifying co-expressed genes, gene families, and co-expression clusters enriched for specific biological functions. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AVAILABILITY: The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

[SLC25A13 gene analysis in neonates with intrahepatic cholestasis caused by citrin deficiency].

OBJECTIVE: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) which resulted from mutation in SLC25A13 gene can present transient intrahepatic cholestasis, low birth weight, growth retardation, hypoproteinemia and so on. This study aimed to identify the mutation type of NICCD patients by DNA sequencing. METHODS: Twenty children diagnosed as NICCD were consented to enroll in this study. PCR assays were performed to amplify the eighteen exons and its flanking sequences of SLC25A13 gene, which were defined as the upstream and downstream 50 bp from starting and ending site of the exons. Then the PCR products were purified and followed by automated DNA sequencing. The IVS16ins3kb mutation was detected by nested PCR and RT-PCR. RESULTS: Seven genetic variations of SLC25A13, termed as 851del4, 1638ins23, IVS16ins3kb, IVS6+5G>A, c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C), were identified in the subjects, of which c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C) were reported for the first time in NICCD patients. And a compound mutation ofï¼»1638ins23+IVS16ins3kbï¼½was also identified. In 20 patients with NICCD, 6 patients were 851del4 homozygotes, 7 patients were compound heterozygotes, and 7 patients were heterozygotes of single mutation. 851del4 was the major mutation type (64%), followed by 1638ins23 (15%), IVS16ins3kb (12%) and IVS6+5G>A (6%). CONCLUSIONS: 851del4 is the major mutation type in Chinese patients with NICCD.

[Efficacy and safety of adjunctive levetiracetam in children younger than 4 years with refractory epilepsy].

OBJECTIVE: To evaluate of the efficacy and safety of adjunctive levetiracetam (LEV) in children younger than 4 years with refractory epilepsy. METHODS: One hundred and twelve children at age of 4 months to 4 years with refractory epilepsy received LEV as adjunctive therapy. LEV was administered in two equal daily doses of 10 mg/kg. The dose was increased by 10 mg/kg every week up to the target dose (20-40 mg/kg). The efficacy and tolerability were evaluated. RESULTS: At an average follow-up period of 13 months (6-22 months), LEV administration was found to be effective in 43 children (38.4%) (responders showing more than a 50% decrease in seizure frequency) and 14 children (12.5%) became seizure-free. Fifty-three children (47.3%) did not respond to the treatment and 2 children (1.8%) worsened. The therapy-related adverse events were mild, including restlessness, reduction in sleep time, night terrors, debility, somnolence, nausea and vomiting. The adverse events were either tolerable or resolved in time with dosage reduction in most of children, and only 3 cases required discontinuation. CONCLUSIONS: LEV as adjunctive therapy is effective and well-tolerated in children younger than 4 years with refractory epilepsy, suggesting that it represents a valid option for the treatment of refractory epilepsy in this age group.

[Benign infantile convulsions with mild gastroenteritis: clinical analysis of 40 cases].

OBJECTIVE: To investigate the pathogenesis, clinical characteristics and treatment of benign infantile convulsions with mild gastroenteritis (BICG). METHODS: The clinical manifestations and laboratory findings were observed in 40 children with BICG. The antigen and antibodies of rotavirus and calicivirus in stool and cerebral spinal fluid (CSF) were tested by the golden standard method and ELISA. The neurological outcome was evaluated by a follow-up of six months or more. RESULTS: All of the 40 children had mild gastroenteritis with or without minor dehydration. Cluster convulsions were observed in these children. There were normal findings in blood biochemistry (Na+, K+, Ca2+, Cl-, HCO3-, glucose) and cerebral CT or MRI examinations. The interictal EEG showed sprinkle central or frontal epileptiform discharges in 8 children; clear central and parietal epileptiform discharges in 1 child; and no abnormal findings were observed in the other 31 children. Positive rotavirus antigen was detected in 11 children and positive calicivirus antigen in stool samples in 4 children. Positive antibodies of rotavirus and calicivirus in CSF were not seen. Seizures recurred in 22 of 28 children who received prophylactic injections of phenobarbital(5-10 mg/kg). In a 6 months follow-up, one child developed epilepsy and the other 39 children had no seizures and neurological sequelae. CONCLUSIONS: The digestive system manifestations are mild in children with BICG. Convulsions are always clustered in these children. The mechanism underlying convulsions is not clear. Conventional dose of phenobarbital is not effective for prevention of seizures. Most of children with BICG have a good prognosis.

The BenBioDen database, a global database for meio-, macro- and megabenthic biomass and densities.

Benthic fauna refers to all fauna that live in or on the seafloor, which researchers typically divide into size classes meiobenthos (32/64 µm-0.5/1 mm), macrobenthos (250 µm-1 cm), and megabenthos (>1 cm). Benthic fauna play important roles in bioturbation activity, mineralization of organic matter, and in marine food webs. Evaluating their role in these ecosystem functions requires knowledge of their global distribution and biomass. We therefore established the BenBioDen database, the largest open-access database for marine benthic biomass and density data compiled so far. In total, it includes 11,792 georeferenced benthic biomass and 51,559 benthic density records from 384 and 600 studies, respectively. We selected all references following the procedure for systematic reviews and meta-analyses, and report biomass records as grams of wet mass, dry mass, or ash-free dry mass, or carbon per m2 and as abundance records as individuals per m2. This database provides a point of reference for future studies on the distribution and biomass of benthic fauna.

[Valproic acid versus lamotrigine as a monotherapy for absence epilepsy in children].

OBJECTIVE: To compare the efficacy of valproic acid (VPA) and lamotrigine as a monotherapy for absence epilepsy in children. METHODS: A randomized, open-label design was used. Childhood absence epilepsy was diagnosed based on the presence of typical seizures and video-EEG findings. Eligible patients were randomly treated with VPA or lamotrigine. All patients were followed up for 12 months. RESULTS: Forty-five out of 48 eligible children completed the study. There were 23 children in the VPA group and 22 children in the lamotrigine group. Seventeen children were seizure-free in the VPA group 12 months after treatment. Fifteen out of the 17 children showed normal EEG (no epileptic-formed discharge). Twelve children were seizure-free in the lamotrigine group 12 months after treatment. The proportion showing normal EEG in the lamotrigine group (6/22, 27.3%) was significantly lower than that in the VPA group (15/23, 65.2%) (P<0.05). Severe adverse effects were not found in both groups. CONCLUSIONS: Both VPA and lamotrigine are safe and efficacious for treatment of absence seizures in children. VPA appears to be better than lamotrigine in tapering epileptic-formed discharge.

[Follow-up of tuberous sclerosis complex complicated by epilepsy in children].

OBJECTIVE: To investigate the treatment outcome and risk factors for intractable seizures in children with tuberous sclerosis complex(TSC)complicated by epilepsy. METHODS: The medical data of 66 cases of TSC were retrospectively studied. RESULTS: Of the 66 children with TSC, 47 cases were available for follow-up. The follow-up period ranged from 7 months to 9.3 years (average 4.5 + or - 2.6 years). The patients' present average age was (7.7 + or - 4.1) years (median 8 years). Among the 47 cases, 19 (40%) had infantile spasms, 24 (51%) had tonic seizures, 15 (32%) had partial seizures, and 3 (6%) had tonic-clonic seizures, and additionally, multifocal seizures, atonic seizures, atypical absence seizures and hypomotor seizures each appeared in 1 case (2%) respectively. The average number of antiepileptic drugs used was 1.9 + or - 0.86 (median 1). Among the 47 patients, 12 (26%) still had epileptic seizures and 33 (70%)were seizure-free, and 4% were dead. Three cases underwent surgery and continued to receive medication after surgery. The three patients were seizure-free in a 1.5 years follow-up. Among the 30 children over 7 years old, 17 cases (57%) were enrolled in ordinary schools, 3 cases (10%) in special schools and the other 10 cases were off-school for disabilities of intelligence and speech. The non-conditional logistic regression showed that the age of onset (RR=1.8, 95% CI 1.0- 3.2, P=0.050), administration of multiple antiepileptic drugs (RR=4.8, 95% CI 1.2-18.6, P=0.024), tonic seizures (RR=0.003, 95% CI 0.0- 0.2, P=0.04) and sex (RR=0.016, 95% CI 0.0-0.5, P=0.017) were risk factors for intractable seizures. CONCLUSIONS: The majority (70%) of children with TSC complicated by epilepsy can be seizure-free with suitable treatment. The risk factors of poor outcome in seizure control may involve in the early onset age, tonic seizures and the administration for multiple anti-epileptic drugs.

[Interictal epileptiform discharges in children with epilepsy].

OBJECTIVE: To study the features of interictal epileptiform discharges (IED) during sleep and wakefulness in children with epilepsy. METHODS: The polysomnography, active EEG and video EEG were performed on 48 children with epilepsy during the whole night, and wakefulness of pre- and post-sleep. The epileptiform sharp/spike discharge indexes during sleep and wakefulness were recorded. The positive rate of IED in focal and generalized epilepsy was compared. RESULTS: Of the 48 patients, 25 showed IED, including 9 cases (36.0%) in the generalized seizure group and 16 cases (64.0%) in the focal seizure group (P<0.05). The epileptiform sharp/spike discharge indexes in the whole non-rapid eye movement (NREM) sleep stage (stages S1-S4: 21.13+/-19.96, 19.59+/-17.76, 22.85+/-18.99, and 20.37+/-16.63) were significantly higher than that in the wakefulness stage (8.20+/-6.21) (P<0.05). The discharge index in the S3 stage during NREM sleep was higher than that during the rapid eye movement (REM) sleep (22.85+/-18.99 vs 12.91+/-10.95; P<0.05). CONCLUSIONS: The positive rate of IED in the focal seizure group was higher than that in the generalized seizure group. Sleep, especially NREM sleep, facilitates IED in children with epilepsy.

[Association of a polymorphism in MDR1 C3435T with response to antiepileptic drug treatment in ethic Han Chinese children with epilepsy].

OBJECTIVE: P-glycoprotein 170 (P-gp) is a plausible biologic candidate for pharmacoresistance in epilepsy. The expression and efflux efficiency of P-gp is influenced by a polymorphism (C3435T) in the encoding gene (MDR1). The CC genotype at the MDR1 C3435T polymorphism was reported to be associated with the response to antiepileptic drug treatment. This study attempted to replicate this finding by examining the association of this genetic polymorphism with response to antiepileptic drug treatment in ethnic Han Chinese children with epilepsy. METHODS: Two hundred and fourteen ethnic Han Chinese children with epilepsy were classified based on the response to antiepileptic drug treatment: drug-nonresponsive and drug-responsive. DNA samples were obtained from the patients. Genotypes of the C3435T polymorphism were determined by traditional polymerase chain reaction followed by restriction digestion (PCR-RFLP). The frequency of genotypes and alleles between the two groups was compared by Chi-square test. RESULTS: Of the 214 patients, 164 were drug-responsive and 50 were drug-nonresponsive. There were no significant differences in the allele frequency and genotype frequency between the two groups. CONCLUSIONS: There is no an association between the CC genotype or C allele at the locus of C3435T in MDR1 gene and response to antiepileptic drug treatment in ethnic Han Chinese children with epilepsy.

Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy.

AIM: To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM. METHODS: A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software. RESULTS: After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing. CONCLUSION: GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.