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Background Epilepsy is a chronic episodic brain disorder with a high incidence and can seriously affect the quality of life of the patients. Therefore, timely treatment to control seizures is particularly important. Numerous studies have shown the effect of antiepileptic drugs on cognition, but there are few studies on the effects of different functional areas in children. Objective To explore the effects of sodium valproate (VPA) , oxcarbazepine (OXC) and levetiracetam (LEV) on the development of different functional areas in children with focal epilepsy by Griffiths Development Scales-Chinese Edition (GDS-C) . Methods A total of 83 children with focal epilepsy who attended in outpatient and ward of the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University for the first time from January 2021 to April 2022 were selected, and randomly divided into VPA group (n=27) , OXC group (n=28) and LEV group (n=28) according to the random number table method, 30 healthy children who were examined during the same period were selected as the control group. The changes of EEG interictal epileptiform activity (IEA) before and after 6 months of treatment were recorded and the clinical effect was evaluated according to seizure frequency, the GDS-C was used to evaluate the development quotient of each functional area in the children. Results The total clinical effective rates of VPA group, OXC group and LEV group were 92.6%, 89.3% and 92.9%, with no significant difference among the three groups (χ2=0.418, P=1.000) . The total EEG IEA effective rate of the VPA group, OXC group and LEV group were 88.9%, 57.1% and 89.3%, with significant differences among the three groups (χ2=11.152, P=0.004) ; the total effective rate of EEG IEA in OXC group was lower than that in VPA group and LEV group (P

Objective: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug‐resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD). Methods: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow‐ups were done to assess post‐surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) were used to examine differential gene expression between the FCD and control groups. Results: Among the 40 patients included in the study, focal to bilateral tonic–clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET‐CT) scans revealed hypometabolic lesions. Fused MRI/PET‐CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET‐CT alone, while 59.26% (16/27) yielded results consistent with PET‐CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow‐up, 38 patients were prescribed an average of 1.27 ± 1.05 anti‐seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow‐up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT‐PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1. Significance: This study highlights focal to bilateral tonic–clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD‐related DRE showed a promising prognosis for seizure control post‐surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD. Plain Language Summary: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic–clonic seizures were the most prevalent seizure type in patients with drug‐resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia‐induced drug‐resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia. [ABSTRACT FROM AUTHOR]

Objective: Defects in RARS2 cause cerebellopontine hypoplasia type 6 (pontocerebellar hypoplasia type 6, PCH6, OMIM: #611523), a rare autosomal recessive inherited mitochondrial disease. Here, we report two male patients and their respective family histories. Methods: We describe the clinical presentation and magnetic resonance imaging (MRI) findings of these patients. Whole‐exome sequencing was used to identify the genetic mutations. Results: One patient showed hypoglycemia, high lactic acid levels (fluctuating from 6.7 to 14.1 mmol/L), and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and pons. The other patient presented with early infantile developmental and epileptic encephalopathies (EIDEEs) with an initial developmental delay followed by infantile epileptic spasm syndrome (IESS) at 5 months old, with no imaging changes. Whole‐exome sequencing identified compound heterozygous RARS2 variants c.25A>G (p.I9V) with c.1261C>T (p.Q421*) and c.1A>G (p.M1V) with c.122A>G (p.D41G) in these two patients. Of these loci, c.1261C>T and c.122A>G have not been previously reported. Significance: Our findings have expanded the RARS2 gene variant spectrum and present EIDEEs and IESS as phenotypes which deepened the association between PCH6 and RARS2. Plain Language Summary: Defects in RARS2 cause cerebellopontine hypoplasia type 6, a rare autosomal recessive inherited mitochondrial disease. Two patients with RARS2 variants were reported in this article. One patient showed hypoglycemia, high lactic acid levels, and frequent seizures after birth, with progressive atrophy of the cerebrum, cerebellum, and Page 3 of 21 Epilepsia OpenFor Review Only pons. The other patient presented with an initial developmental delay followed by refractory epilepsy at 5 months old, with no imaging changes. Our findings deepened the association between PCH6 and RARS2. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of GABRG2 -related epilepsy and its prognosis and to explore the potential prospects for personalized medicine. Methods: Through a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with GABRG2 -related epilepsy. The three-dimensional protein structure of the GABRG2 variant was modeled to predict the effect of GABRG2 missense variants using PyMOL 2.3 software. Results: In 35 patients with GABRG2 variants, 22 variants were de novo , and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The proportions of patients with missense variants in the extracellular region and the transmembrane region exhibiting developmental delay were 40% and 63.2%, respectively. The last follow-up age ranged from 11 months to 17 years. Seizures were controlled in 71.4% of patients, and 92% of their seizures were controlled by valproate and/or levetiracetam. Conclusion: The clinical features of GABRG2 -related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. More than half of the patients had cluster seizures. Phenotypes of GABRG2 -related epilepsy were ranged from mild febrile seizures to severe epileptic encephalopathies. Most patients with GABRG2 variants who experienced seizures had a good prognosis. Valproate and levetiracetam were effective treatments for most patients. [ABSTRACT FROM AUTHOR]

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A novel and versatile approach to the preparation of multitype polymers brushes on the quantum dots surface is reported. In this method, an azo initiator is first immobilized covalently onto CdSe/CdS particle surface by reacting with the 4,4′-Azobis (4-cyanovaleric acid) through an ester linkage. CdSe/CdS nanoparticles with polymer brushes (CdSe/CdS-polymers) of different properties, including hydrophilic polyacrylamide, poly(acrylic acid), and poly(vinyl pyrrolidone); hydrophobic oleophilic poly(vinyl acetate), poly(methyl acrylate), and poly(methyl methacrylate); polystyrene with conjugate group; and polyacrylonitrile with strong polarity group, are synthesized by one approach (the surface-initiated radical poly­merization technique), respectively. The structures and properties of CdSe/CdS-polymers reveal that the CdSe/CdS-azo initiator has excellent ability to initiate various kinds of vinyl monomers and these synthetic CdSe/CdS-polymers exhibit good stability and can emit multiple colors from the emission 405 to 569 nm. Moreover, CdSe/CdS-polymers brushes show characteristic micromorphologies. Such strategy provides a platform to achieve nanocomposites with different properties by a new CdSe/CdS-azo initiator through the simple conventional radical polymerization technique. Besides, the synthetic approach gives access to multitype modification of different nanoparticles with polymers. [ABSTRACT FROM AUTHOR]

Mental retardation-40 (MRD40) is a rare autosomal dominant neurodevelopmental disorder with a poor prognosis that is caused by a heterozygous mutation in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). It was previously considered a non-syndromic disease due to the lack of specific external features. Only limited international reports describing CHAMP1 mutations are currently available. The present case study was the first to report on a Chinese patient with MRD40. The patient presented with severe global development delay with significant craniofacial dysmorphia. Using trio whole-exome sequencing, a novel de novo frameshift mutation in CHAMP1, NM_032436.2: c.530delCinsTTT, was identified, which expands the spectrum of the known pathogenic variants. The present case report helps to improve the syndromic profile of the rare MRD40 disorder and provides an example for the clinical diagnosis of MRD40. [ABSTRACT FROM AUTHOR]

Leptin has been found to be involved in the ovarian granulosa cell apoptosis and steroidogenesis. Loss of neuropeptide Y (NPY) can correct the obesity syndrome of mutant mice lacking of leptin (ob/ob). However, the association of NPY and leptin in ovarian granulosa cells and ovarian steroidogenesis has not been investigated. Here, C57BL/6J ob/ob mice and C57BL/6J (control) mice were intraperitoneally injected with PBS, leptin (0.4 μg/g bodyweight) or BIIE0246 (NPY2 receptor [NPY2R] antagonist, 30 μg/kg bodyweight) every day for 15 days. We found that NPY2R mRNA expression in mouse ovary was suppressed by leptin treatment, but increased by leptin deficiency. Leptin or BIIE0246 treatment significantly increased E2, but notably decreased progesterone in both mice. A lower level of E2 and a higher level of progesterone was observed in ob/ob mice than in control mice. Further, we then knocked down leptin expression in human ovarian granulosa cells by siRNA transfection and treated the cells with DMSO or BIIE0246. In vitro experiments confirmed the findings in mice. siLeptin treatment decreased the secretion of E2, anti-Mullerian hormone (AMH), insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β, and the cell proliferation, but increased the secretion of progesterone and cell apoptosis. Western blotting analysis of PCNA, Bcl-2 and Bax confirmed the results of cell proliferation and apoptosis. Activation of JAK2 and STAT3 was also suppressed by knocking down leptin. All the effects of siLeptin on ovarian granulosa cells were partially reversed by BIIE0246. In conclusion, knockdown of leptin significantly affected ovarian steroidogenesis and ovarian function through NPY. siLeptin transfection impaired the activation of JAK2/STAT3 and contributed to ovarian granulosa cell apoptosis partially through up-regulating NPY2R expression. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical and genetic characteristics of three children with Hyperekplexia., Methods: Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis., Results: The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c.1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment., Conclusion: Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.

Objective: This study aims to describe the characteristics of the brain network attributes in children diagnosed with Infantile Epileptic Spasms Syndrome (IESS) and to determine the influence exerted by adrenocorticotrophic hormone (ACTH) or methylprednisolone (MP) on network attributes., Methods: In this retrospective cohort study, we recruited 19 infants diagnosed with IESS and 10 healthy subjects as the control from the Pediatric Neurology Department at the Third Affiliated Hospital of Zhengzhou University between October 2019 and December 2020. The first thirty-minute processed electroencephalograms (EEGs) were clipped and filtered into EEG frequency bands (2 s each). A comparative assessment was conducted between the IESS group and the controls as well as the pre- and post-treatment in the IESS group. Mutual information values for each EEG channel were collected and compared including characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC), based on graph theory., Results: Comparing the control group, in the IESS group, there was an increase in CPL of the Delta band, and a decrease in ND and CC of the Delta band during the waking period, contrary to those during the sleeping period ( P  < 0.05), a decreased in CPL of the fast waves and an increase in ND and CC ( P  < 0.05) in the sleep-wake cycle, and a decrease in ND and CC of the Theta band in the waking phase. Post-treatment compared with the pre-treatment, during the waking ictal phase, there was a noted decrease in CPL in the Delta band and fast waves, while an increase was observed in ND and CC ( P  < 0.05)., Conclusions: The Delta band and fast waves are crucial components of the network attributes in IESS., Significance: This investigation provides a precise characterization of the brain network in children afflicted with IESS, and lays the groundwork for predicting the prognosis using graph theory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dong, Jin, Li, Lian, Wu, Xu, Zhang, Du, Jia, Wang and Zhao.)

Background and Aims: Joubert syndrome (JBTS, OMIM # 213300) is a group of ciliopathies characterized by mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia, and breathing abnormalities. Molar tooth sign in brain imaging is the hallmark for diagnosing JBTS. It is a clinically and genetically heterogeneous disorder involving mutations in more than 40 ciliopathy-related genes. However, long-term follow-up data are scarce, and further research is needed to determine the abundant phenotypes and genetics of this disorder. The study aimed to summarize clinical manifestations, particular appearance on cranial imaging, genetic data, and prognostic features of patients with JBTS., Methods: A retrospective case review of 36 cases of JBTS from May 1986 to December 2021 was performed. Clinical data of JBTS patients with development retardation and molar tooth sign on cranial imaging as the main features were analyzed. Genetic testing was performed according to consent obtained from patients and their families. The Gesell Developmental Scale was used to evaluate the intelligence level before and after treatment. The children were divided into a purely neurological JBTS (pure JBTS) group and JBTS with multi-organ system involvement group and then followed up every 3-6 months., Results: We enrolled 18 males and 18 females. Thirty-four (94.44%) cases had developmental delay, one patient (2.78%) had strabismus, and one patient (2.78%) had intermittent dizziness. There was one case co-morbid with Lesch-Nyhan syndrome. Three-quarters of cases had one or more other organ or system involvement, with a greater predilection for vision and hearing impairment. JBTS could also involve the skin. Thirty-one cases (86.11%) showed a typical molar tooth sign, and five cases showed a bat wing sign on cranial imaging. Abnormal video electroencephalogram (VEEG) result was obtained in 7.69% of cases. We found six JBTS-related novel gene loci variants: CPLANE1 : c.4189 + 1G > A, c.3101T > C(p.Ile1034Thr), c.3733T > C (p.Cys1245Arg), c.4080G > A(p.Lys1360=); RPGRIP1l : c.1351-11A > G; CEP120 : c.214 C > T(p.Arg72Cys). The CHD7 gene may be potentially related to the occurrence of JBTS. Analysis showed that the prognosis of pure JBTS was better than that of JBTS with neurological and non-neurological involvement after the formal rehabilitation treatment ( P  < 0.05). Of the three children with seizures, two cases had epilepsy with a poor prognosis, and another case had breath-holding spells., Conclusion: Our findings indicate that early cranial imaging is helpful for the etiological diagnosis of children with unexplained developmental delay and multiple malformations. Patients with JBTS may have coexisting skin abnormalities. The novel gene loci of CPLANE1 , RPGRIP1l , and CEP120 were associated with JBTS in our study and provided significant information to enrich the related genetic data. Future works investigating several aspects of the association between CHD7 gene and JBTS merit further investigation. The prognosis of children with pure JBTS is better than that of children with JBTS with non-neurological involvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Dong, Zhang, Yao, Jia, Wang, Zhu, Xu, Cheng, Zhao and Shi.)

Background: Intellectual disability, X-linked, syndromic, Christianson type (MRXSCH, OMIM: 300243)-known as Christianson syndrome (CS)-is characterized by microcephaly, epilepsy, ataxia, and absence of verbal language ability. CS is attributed to mutations in the solute carrier family 9 member A6 gene ( SLC9A6 )., Materials and Methods: This study reports the case of a boy 1 year and 3 months of age who was diagnosed with CS in our department. Genetic etiology was determined by whole-exome sequencing, and a minigene splicing assay was used to verify whether the mutation affected splicing. A literature review of CS cases was conducted and the clinical and genetic features were summarized., Results: The main clinical manifestations of CS include seizures, developmental regression, and exceptional facial features. Whole-exome sequencing revealed a de novo splice variant in intron 11 (c.1366 + 1G > C) of SLC9A6 . The mutation produced two abnormal mRNA products (verified by a minigene splicing assay), resulting in the formation of truncated protein. A total of 95 CS cases were identified in the literature, with various symptoms, such as delayed intellectual development (95/95, 100.00%), epilepsy (87/88, 98.86%), and absent verbal language (75/83, 90.36%). At least 50 pathogenic variants of SLC9A6 have been identified, with the highest frequency observed in exon 12., Conclusion: Our patient is the first case with the c.1366 + 1G > C variant of SLC9A6 in CS. The summary of known cases can serve as a reference for analyzing the mutation spectrum and pathogenesis of CS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Lian, Jin, Zhao, Tao, Wang, Li, Jia, Chen and Cao.)

Objective: The study aimed to identify the signatures of brain networks using electroencephalogram (EEG) in patients with infantile spasms (IS)., Methods: Scalp EEGs of subjects with IS were prospectively collected in the first year of life ( n = 8; age range 4-8 months; 3 males, 5 females). Ten minutes of ictal and interictal EEGs were clipped and filtered into different EEG frequency bands. The values of each pair of EEG channels were directly compared between ictal with interictal onsets and the sleep-wake phase to calculate IS brain network attributes: characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC)., Results: CPL, ND, and CC of the fast waves decreased while BC increased. CPL and BC of the slow waves decreased, while ND and CC increased during the IS ictal onset ( P < 0.05). CPL of the alpha decreased, and BC increased during the waking time ( P < 0.05)., Conclusion: The transmission capability of the fast waves, the local connectivity, and the defense capability of the slow waves during the IS ictal onset were enhanced. The alpha band played the most important role in both the global and local networks during the waking time. These may represent the brain network signatures of IS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dong, Xu, Zhang, Shi, Du, Jia, Wang and Wang.)

Objective: To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome., Methods: The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents., Results: Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c.4015C>T (exon 17) and c.5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c.6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient' s clinical phenotype., Conclusion: The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.

Background: Krabbe disease, also called globoid cell leukodystrophy, is an autosomal recessive disease caused by a deficiency of lysosomal galactocerebrosidase. Infantile Krabbe occurring before 12 months of age accounts for most cases. Typical clinical features include irritability, seizures, peripheral neuropathy, and progressive neurodegeneration., Methods: We collected and summarized the clinical and genetic data of an 8-month-old boy who demonstrated Krabbe disease onset at around 6 months. Potential pathogenic variants were screened by whole exome sequencing, and effects of candidate variants on alternative transcript and truncated protein were further validated at the RNA and protein level., Results: Galactocerebrosidase activity was nearly absent in his blood, and whole exome sequencing revealed compound heterozygous variants [NM&#95;000153.4: (c.658C>T); (c.328+5G>T)] in galactosylceramidase ( GALC ). The variant c.328+5G>T was predicted to alter splicing, and the abnormal isoform transcript was validated by observation of abnormal RNA isoforms. The variant c.658C>T was predicted to cause truncation of the protein, which was validated by western blotting., Conclusions: Our findings revealed compound heterozygous variants with solid experimental results for Krabbe disease and provides strong evidence for further Krabbe disease screening and clinical consulting. As a rare inherited systemic disorder, genetic variants in Krabbe disease should be investigated, as experimental validation for clinical diagnosis is needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tp-21-403). The authors have no conflicts of interest to declare., (2021 Translational Pediatrics. All rights reserved.)

Objective: To explore the genetic basis for three children with Menkes disease., Methods: The patients were subjected to next-generation sequencing (NGS) to detect potential variants of the ATP7A gene. Suspected variants were verified by Sanger sequencing of their family members and 200 healthy individuals. Multiplex ligation-dependent probe amplification (MLPA) was also carried out to detect potential deletions in their family members and 20 healthy individuals., Results: Variants of the ATP7A gene were detected in all of the three families, including a novel c.1465A>T nonsense variant in family 1, a novel c.3039&#95;3043del frame-shifting variant in family 2, and deletion of exons 3 to 23 in family 3, which was reported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.1465A>T and c.3039&#95;3043del variants of ATP7A gene were predicted to be likely pathogenic (PVS1+PM2)., Conclusion: Variants of the ATP7A gene may underlay the Menkes disease in the three children. Above findings have facilitated clinical diagnosis and enriched the spectrum of genetic variants of Menkes disease.