Abstract The ketogenic diet (KD) is an established non-pharmacological treatment for drug-resistant epilepsy (DRE) in children, but data from large prospective cohorts in China remain limited. We conducted a prospective observational study of children with DRE whose caregivers elected KD treatment compared with those who continued conventional therapy. Seizure frequency, EEG findings, cognitive assessments, and adverse events were monitored over six months. A total of 136 children were enrolled (73 KD; 63 controls). At six months, children receiving KD showed a higher proportion of seizure reduction ≥ 50% compared with controls. EEG evaluations revealed improvements in background activity and reduction in epileptiform discharges, and cognitive assessments demonstrated gains in specific domains. Adverse effects were generally mild and manageable with dietary adjustments. In this single-center prospective cohort, KD was associated with improved seizure control, EEG patterns, and cognitive performance over six months compared with conventional therapy. While limited by non-randomized design and short follow-up, these findings provide real-world evidence supporting KD as a feasible and safe adjunctive therapy for pediatric DRE in China. Longer randomized studies are warranted to establish causality and evaluate long-term outcomes.

OBJECTIVE:The CDK5RAP2 gene, which encodes a regulator of cyclin-dependent kinase activity, plays a vital role in brain development. CDK5RAP2 variants have been previously reported in patients with primary microcephaly-3, with or without epilepsy. This study aimed to investigate the association between CDK5RAP2 and epilepsy. METHOD:Trio-based whole-exome sequencing was performed in patients with idiopathic focal epilepsy without acquired causes. Sub-regional effects, genotype-phenotype correlation, and protein-protein interactions were analysed to reveal gene-disease association. RESULTS:Four compound heterozygous CDK5RAP2 variants were identified in four unrelated cases. These variants had no or extremely low allele frequencies in the controls and showed statistically higher frequencies than those in the controls. These variants were predicted to have changes in hydrogen bonds, decreased protein stability, and significant alterations in the hydrophobicity. All patients had focal epilepsy without microcephaly. Patient in one case with two variants of paired missense variants located at the functional domain showed refractory seizures, whereas another patient with variants outside functional domains was seizure-free, suggesting a potential sub-regional effect. The proportion of missense variants in the epilepsy group was significantly higher than that in the primary microcephaly group, suggesting a potential genotype-phenotype correlation. Protein-protein interaction analysis showed that CDK5RAP2 interacted with 31 proteins with high confidence, of which 13 genes were associated with epilepsy and neurodevelopmental disorders, suggesting a potential association between CDK5RAP2 and epilepsy. CONCLUSION:CDK5RAP2 is a novel causative gene for focal epilepsy without microcephaly.

OBJECTIVE:The BRSK1 gene encodes brain-specific serine/threonine kinase 1 (also known as SAD-B kinase), which is almost exclusively expressed in the brain and plays critical roles in neuronal polarization, neurotransmitter release, mitochondrial dynamics, and neuronal maturation. This study aimed to investigate the pathogenicity of BRSK1 variants in epilepsy and neurodevelopmental disorders. METHODS:Trio-based exome sequencing was performed in 394 probands with epilepsy. Expression analyses and functional validation were conducted using a newly generated Brsk1 exon 4-7 knockout mouse line (Brsk1Δ4-7), with subsequent behavioral, electrophysiological, proteomic, and phosphoproteomic assessments. RESULTS:Six novel BRSK1 variants were identified in seven probands, including four single nucleotide variants (SNVs) and two indels; five were de novo, one inherited, and one recurrent. Frameshift or nonsense variants led to complete loss of detectable BRSK1 protein, whereas one missense variant reduced protein levels. Both heterozygous and homozygous Brsk1Δ4-7 mice exhibit increased seizure susceptibility, neuronal hyperexcitability, and neurobehavioral impairments-recapitulating key clinical features associated with BRSK1 haploinsufficiency in humans. Proteomic and phosphoproteomic analyses revealed dysregulation of pathways critical for axonal development and synaptic function. SIGNIFICANCE:Our genomic and functional studies strongly support BRSK1 haploinsufficiency as a pathogenic mechanism in a human epilepsy syndrome. To our knowledge, this is the first study to implicate the brain-specific serine/threonine kinase BRSK1 in epilepsy and neurodevelopmental disorders.

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 2022were 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＜0.05）. Before treatment,there were statistically significant differences in the the development quotient of each dimension among four groups（P＜0.05）;the development quotient of each dimension in three groups were lower than that in the control group（P＜0.05）. After treatment,there were significant differences in the the development quotients of hand-eye coordination and performance dimensions among three groups（P＜0.05）;the development quotients of sports and personal-social dimensions in LEV group were higher than VPA group（P＜0.05）,the development quotients of personal-social,hand-eye coordination and performance dimensions in LEV group were higher than OXC group（P＜0.05）. Compared to the pre-treatment period,the development quotients of personal-social and practical reasoning dimensions significantly decreased in VPA group（P＜0.05）,the development quotients of personal-social,language,hand-eye coordination,performance and practical reasoning dimensions significantly increased（P＜0.05）. Conclusion VPA,OXC and LEV are all effective in the treatment of focal epilepsy in children,and all three have quivalent efficacy;In terms of improving EEG IEA,OXC is inferior to VPA and LEV;VPA may have a negative effect on personal-social and practical reasoning dimensions,OXC has little effect,and LEV may have improvement on personal-social,language,hand-eye coordination,performance,practical reasoning dimensions.

ObjectiveThis 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.MethodsIn 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.ResultsComparing 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).ConclusionsThe Delta band and fast waves are crucial components of the network attributes in IESS.SignificanceThis 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.

Objective To analyze the clinical data of 2 cases of CHD2 gene related epilepsy and to investigate their phenotypes and gene mutation types. Methods The clinical data of 2 probands and their families were collected. The peripheral blood of the probands and their parents was extracted for genomic DNA. High-throughput sequencing was used to detect the exons and their intronic regions to define the gene mutation sites, and the pathogenic variations were verified by PCR-Sanger sequencing. The conservativeness of gene variation sites in the probands was analyzed by UCSC softwares, and the pathogenicity of variation sites was analyzed by using the Varseak and Mutation Taster softwares. Results Convulsions developed in two patients at the age of about 3 years old. Proband 1 was manifested with tonic-clonic seizures, which was controlled by levetiracetam and sodium valproate treatment after being diagnosed as epilepsy and autism spectrum disorder. This proband was detected heterozygous mutation of CHD2 gene c.2877-1＿2877delGCinsAA, which was a splicing receptor mutation. The corresponding base（C） at C.2877-1 and the corresponding amino acid（asparagine） at c.2877 were highly conserved in 13 species. Parental verification and query of human gene database indicated that it was a de novo mutation. The analysis results of Varseak predicted that the mutation would lead to changes in protein sequence and structure, and was possibly pathogenic according to the ACMG classification. Proband 2 was diagnosed with Lennox-Gastaut syndrome, with multiple seizure patterns combined with severe developmental delay. Seizures were controlled after treatment with levetiracetam, while other drugs had poor efficacy. There was a heterozygous mutation of CHD2 gene c.361C＞T（p.Arg121Ter）,which was a nonsense mutation.The 121amino acid（arginine）corresponding to the c.361C＞T mutation was highly conserved in 13species.The mutation was verified as a de novo mutation in the pedigree,Mutation Taster software analysis indicated that it was suspected to be pathogenic mutation,and it was pathogenic according to the ACMG classification.Conclusion The children with epilepsy accompanied by developmental delay and autism spectrum disorder should consider the CHD2 gene mutation,and genetic test contributes to the early diagnosis.

目的 观察癫痫患儿规范应用抗癫痫发作药物(antiseizure medications,ASMs)或联合糖皮质激素治疗后低纤维蛋白原血症发生情况及严重程度,探讨抗癫痫治疗后发生低纤维蛋白原血症的因素和治疗结局.方法 33例应用ASMs或联合糖皮质激素规范治疗后发生低纤维蛋白原血症的癫痫患儿,确诊低纤维蛋白原血症后给予人纤维蛋白原、必要时降低丙戊酸钠药物剂量等治疗.记录癫痫发作类型、综合征类型、病因、治疗后发生低纤维蛋白原血症的中位时间、发生低纤维蛋白原血症时的治疗方案;于抗癫痫治疗前、诊断低纤维蛋白原血症时、低纤维蛋白原血症治疗次日及治疗后1个月检测纤维蛋白原(fibrinogen,Fib)、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间、纤维蛋白降解产物、D-二聚体、中性粒细胞计数、白细胞计数、血红蛋白、血小板计数.随访至2022年8月,观察患儿低纤维蛋白原血症复发情况.结果 33例发作类型为痉挛发作24例,强直-阵挛发作6例,强直痉挛发作2例,肌阵挛发作1例;婴儿癫痫性痉挛综合征21例;病因不明14例,结构性病因13例,遗传性病因6例;1例因不易止血发现且合并轻度肝功能损伤,余32例在随访期间常规检测血常规、凝血功能时发现.诊断低纤维蛋白原血症时,33例中32例应用丙戊酸钠,其中26例(含21例婴儿癫痫性痉挛综合征)应用糖皮质激素联合丙戊酸钠等ASMs,1例应用糖皮质激素联合左乙拉西坦、托吡酯及氯硝西泮,6例未应用糖皮质激素(5例应用丙戊酸钠联合其他ASMs,1例单用丙戊酸钠).诊断低纤维蛋白原血症时Fib水平[0.930(0.850,0.980)g/L]低于抗癫痫治疗前[2.460(2.140,2.675)g/L](Z=-5.013,P＜0.001),凝血酶时间[(20.676±1.756)s]长于抗癫痫治疗前[(18.284±1.605)s](t=7.478,P＜0.001),活化部分凝血活酶时间[(34.803±5.446)s]短于抗癫痫治疗前[(40.447±5.402)s](t=-6.030,P＜0.001).31例诊断低纤维蛋白原血症时Fib水平＜1.0 g/L,静脉滴注人纤维蛋白原,30例应用丙戊酸钠者同时口服左卡尼汀,次日低纤维蛋白原血症纠正;2例诊断低纤维蛋白原血症时Fib水平为1.0 g/L,口服左卡尼汀并降低丙戊酸钠剂量后低纤维蛋白原血症得到纠正.33例低纤维蛋白原血症治疗次日Fib水平[1.950(1.515,2.490)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶原时间[(12.564±1.140)s]、凝血酶时间[(17.491±1.515)s]均短于诊断低纤维蛋白原血症时[(13.752±1.591)、(20.676±1.756)s](P＜0.05);低纤维蛋白原血症治疗1个月Fib水平[1.550(1.390,1.659)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶时间[(17.680±1.465)s]短于诊断低纤维蛋白原血症时(P＜0.05),活化部分凝血活酶时间[(37.601±5.728)s]长于诊断低纤维蛋白原血症时(P＜0.05).中位随访32.75(24.90,43.88)个月,1例间隔2个月再次发生低纤维蛋白原血症,再次静脉滴注人纤维蛋白原并降低丙戊酸钠剂量后纠正,余患儿未再发生低纤维蛋白原血症.结论 应用丙戊酸钠或联合糖皮质激素治疗、发作类型为婴儿癫痫性痉挛综合征的癫痫患儿易发生低纤维蛋白原血症,临床应注意监测癫痫患儿凝血功能,发现低纤维蛋白原血症后及时处理,减少相关出血并发症.

Abstract 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.

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.

Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.

BACKGROUND AND OBJECTIVE:Asparagine synthetase deficiency (ASNSD) is a rare neurometabolic disease caused by variations of the ASNS gene. It manifests as microcephaly, severe developmental delay, and spastic quadriplegia. 71% of ASNSD patients died during early infancy. We aim to investigate mutations related to intractable epilepsy in one Chinese genealogy.MATERIAL AND METHODS:Head Magnetic Resonance Imaging (MRI), whole exome sequencing (WES), and Liquid Chromatography-Mass Spectrometry (LC-MS) to help 2 patients with intractable epilepsy find the underlying mechanisms of disease.RESULTS:These two patients had a compound heterozygous mutation (c.224A > G, p.N75S and c.1612A > G, p.M538V) in the ASNS gene, of which c.1612A > G was a novel mutation. The asparagine levels in patients' plasmas were normal. In addition, they had a later onset, longer survival, and were milder than previously reported ASNSD patients.CONCLUSIONS:Two patients were diagnosed with a milder form of ASNSD. Clinically, the asparagine level in the patient's plasma cannot be used as the only basis to diagnose this disease. This study has expanded the disease phenotype spectrum of ASNSD and broadened the variation profile of the ASNS gene, which can assist in the clinical diagnosis and treatment of ASNSD patients.

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.

Objective:To investigate the risk factors for cerebral injury in survivors of twin-to-twin transfusion syndrome (TTTS) after fetoscopic laser occlusion of chorioangiopagous vessels(FLOC) and to analyze the neurodevelopmental outcomes at 12 months of corrected age.Methods:A total of 136 cases of TTTS receiving FLOC in the Third Affiliated Hospital of Zhengzhou University from May 2018 to August 2021 were retrospectively selected as the FLOC group, and the survivors were followed up. Neurological development at 12 months of corrected age was assessed using the Griffiths mental development scales-Chinese (GDS-C) from five dimensions with locomotor, personal-social, hearing and language, hand-eye coordination and performance subscales. Eighty-eight fetuses of TTTS pregnancies receiving expectant treatment or amniotic fluid reduction were selected as the non-FLOC group. The perinatal mortality and the incidence of cerebral injury in the two groups were compared, as well as the incidence of cerebral injury between patients undergoing Solomon surgery and selective laser surgery in the FLOC group. Generalized estimating equations were used to analyze the risk factors for neonatal cerebral injury after FLOC and the factors influencing general developmental quotient score at the corrected age of 12 months. Chi-square test, t-test, and Mann-Whitney U test were used for statistical analysis. Results:(1) The perinatal mortality rate in the FLOC group was lower than that in the non-FLOC group [14.7% (20/136) vs 26.1% (23/88), χ 2=4.50, P=0.034]. There was no statistical significance in the incidence of neonatal cerebral injury between the two groups [18.7% (23/123) vs 21.8% (17/78), χ 2=0.29, P=0.592], but the incidence of severe cerebral injury in the FLOC group was lower than that in the non-FLOC group [6.5% (8/123) vs 15.4% (12/78), χ 2=4.20, P=0.040]. (2) In the FLOC group, there was no significant difference in the incidence of cerebral injury between donors and recipients, or between Solomon surgery and selective laser surgery [16.4% (10/61) vs 21.0% (13/62), χ 2=0.42; 20.0% (9/45) vs 17.9% (14/78), χ 2=0.08; both P>0.05]. (3) Multivariate analysis showed that neonatal asphyxia ( OR=7.04, 95% CI: 1.45-34.20, P=0.016) and higher preoperative TTTS stage ( OR=2.05, 95% CI: 1.10-3.82, P=0.023) were risk factors for neonatal cerebral injury. (4) Fifty-two cases were successfully followed up at the corrected age of 12 months, and the incidence of developmental delay in at least one dimension was 34.6% (18/52). Developmental delay was mainly manifested in locomotor skills and language, accounting for 26.9% (14/52) and 11.5% (6/52). No significant difference in Z value was found between recipients and donors in each dimension (all P>0.05). Solomon surgery, larger gestational age at operation and low birth weight were related to low general developmental quotient score (95% CI:－11.71 to－0.23，－1.99 to－0.47，0.00-0.01，respectively，all P<0.05). Conclusions:The occurrence of cerebral injury in TTTS survivors after FLOC is related to preoperative TTTS staging and intrapartum neonatal asphyxia. Neurodevelopment of survivors is related to birth weight and gestational age at surgery, and there is a higher incidence of mild developmental delay at corrected age of 12 months.

目的 观察清醒期、睡眠期婴儿痉挛症(infantile spasms,IS)患儿痉挛发作期间不同频段脑功能网络属性特征路径长度(characteristic path length,CPL)的变化,探讨激素冲击治疗对IS患儿脑功能网络的作用.方法 IS患儿19例(IS组),均行甲泼尼龙或促肾上腺皮质激素冲击治疗;记录IS组激素冲击治疗前、后清醒期、睡眠期、清醒发作期、睡眠发作期脑电图数据,应用matlab软件分析delta、theta、alpha、beta、gamma频段CPL.选取同期行视频脑电图检查结果正常的儿童10例为对照组,比较2组清醒期、睡眠期脑电图delta、theta、alpha、beta、gamma频段CPL.随访1年,观察IS患儿激素冲击治疗后痉挛发作的控制情况.结果 随访1年,痉挛发作完全控制11例,治疗无效8例.激素冲击治疗前IS组患儿清醒期脑电图delta频段CPL[130.79(121.61,144.74)×10-3]高于对照组[128.50(119.11,140.78)×10-3](Z=-2.645,P=0.008),beta、gamma 频段 CPL[89.72(78.65,65 535.00)×10-3、94.22(83.98,65 535.00)×10-3]均低于对照组[107.87(90.37,65 535.00)×10-3、98.33(88.53,65 535.00)×10-3](Z=-9.236,P＜0.001;Z=-3.282,P=0.001);睡眠期脑电图 delta、beta 频段 CPL[129.17(118.06,140.99)×10-3、82.80(74.14,113.68)×10-3]均低于对照组[131.90(122.48,141.69)×10-3、92.38(76.94,65 535.00)×10-3](Z=-2.688,P=0.007;Z=-5.079,P＜0.001).清醒期IS组患儿激素冲击治疗后脑电图beta、gamma频段CPL[94.37(83.64,65 535.00)×10-3、97.98(88.04,65 535.00)×10-3]均高于激素冲击治疗前(Z=-4.503,P＜0.001;Z=-3.611,P＜0.001);睡眠期IS组患儿激素冲击治疗后脑电图beta频段CPL[89.65(79.43,65 535.00)×10-3]高于激素冲击治疗前(Z=-7.311,P＜0.001).IS患儿激素冲击治疗后清醒发作期脑电图delta、alpha、beta、gamma频段CPL[111.73(106.44,117.92)×10-3、110.75(103.97,130.07)×10-3、81.35(74.07,97.43)×10-3、92.61(79.01,65 535.00)×10-3]均低于冲击治疗前[118.16(110.58,130.23)×10-3、115.19(104.83,162.77)×10-3、90.53(76.98,65 535.00)×10-3、96.17(82.78,65 535.00)×10-3](P＜0.05);睡眠发作期脑电图 delta 频段 CPL[116.50(109.31,128.12)×10-3]高于冲击治疗前[113.66(107.56,121.60)×10-3](Z=-4.412,P＜0.001),theta 频段 CPL[131.56(114.90,177.63)×10-3]低于冲击治疗前[153.11(127.55,65 535.00)×10-3](Z=-6.109,P＜0.001).结论 IS患儿清醒期、睡眠期脑电图beta频段传输效率增强,激素冲击治疗可降低发作间期beta频段、睡眠发作期delta频段的传输效率,增强清醒发作期delta、alpha、beta、gamma频段的传输效率,改善脑电图高峰失律、减少高频振荡募集可能.

目的 探讨儿童自身免疫性脑炎早期脑电图特点,为免疫性脑炎的早期诊治提供客观依据.方法 回顾性分析32例自身免疫性脑炎患儿[8例为抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎,24例为抗体阴性自身免疫性脑炎]的视频脑电图及动态脑电图资料,分析脑电图背景、临床发作期放电部位、发作间期癫痫样放电及亚临床癫痫发作情况.结果 脑电图异常30例,脑电图正常2例.30例脑电图异常患儿均有背景慢化,其中背景为δ波者16例(53.3％).脑电图显示,睡眠周期紊乱者6例(20.0％).发作间期异常放电14例(46.7％),均为局灶性放电,其中6例脑电图监测期间出现抽搐发作,均为局灶起源,其中1例前额有δ节律;18例无异常放电.结论 儿童自身免疫性脑炎的脑电图主要表现为弥漫性δ波,发作期放电部位主要以颞部为主,发作间期癫痫样放电主要分布于额颞部.

目的 研究临床路径教学在小儿神经内科临床教学中的应用.方法 将于2018年1月—2020年1月期间60名在本院儿科实习的本科生随机平均分为两组,分别进行传统带教及临床路径带教,最后通过考核及问卷评分进行评价.结果 两组学生的理论成绩差异无统计学意义(P>0.05),而实验组实践成绩较对照组高,且通过对学生调查问卷评价教学效果,发现学生对于临床路径教学法的教学内容、教学方式、授课态度、学习积极性及参与度较高,差异均有统计学意义(P<0.05).结论 与传统教学相比,临床路径教学法有效提高小儿神经内科临床教学的实践成绩,增加学生实习的主动性、能动性,对增强学生临床实践能力、提高学生对临床教学的积极性、提高教师的教学质量有重要意义.

目的 探讨脑脊液中纤维连接蛋白(FN)、血管内皮生长因子(VEGF)及乳酸脱氢酶(LDH)水平在鉴别诊断儿童细菌性脑膜炎(BM)和病毒性脑炎(VE)中的价值.方法 选取31例BM患儿(BM组)、34例VE患儿(VE组)及26例非中枢神经系统(CNS)感染患儿(对照组)为研究对象.采用酶联免疫吸附法(ELISA)检测3组患儿治疗前后脑脊液中FN、VEGF、LDH水平;采用受试者工作特征(ROC)曲线分析FN、VEGF及LDH对BM、VE的鉴别诊断价值,采用Pearson系数分析三者的相关性.结果 治疗前,BM组FN、VEGF、LDH水平均高于对照组及VE组,VE组FN水平低于对照组,差异有统计学意义(P＜0.05).治疗后,BM组FN、VEGF、LDH水平降低,VE组FN、LDH水平均降低,差异有统计学意义(P＜0.05).FN、VEGF及LDH鉴别诊断BM组与VE组、BM组和对照组的ROC曲线下面积(AUC)均＞0.9,FN鉴别诊断VE组和对照组的AUC＞ 0.8,但VEGF及LDH鉴别诊断VE组和对照组的AUC ＜0.6.BM组中FN、VEGF及LDH之间两两呈正相关,VE组中VEGF与LDH呈正相关,而对照组中FN、VEGF及LDH之间无相关性.结论 检测脑脊液中FN、VEGF、LDH水平对BM、VE和非CNS感染的鉴别诊断具有一定临床价值.

目的探讨Cornelia de Lange综合征（CdLS）的临床表型及基因型特点。方法回顾分析1例确诊CdLS患儿的临床资料,并总结分析国内已报道病例的情况。结果女性患儿,1岁2月龄,有特殊外貌,智力及运动发育落后,合并四肢畸形及听力异常。基因检测发现患儿HDAC8基因c.675C＞A（p.Y225X）存在新发杂合无义变异,根据ACMG指南预测为致病性变异,确诊CdLS。通过对万方、维普、中国知网及PubMed数据库搜索,发现国内报道CdLS病例46例。其中26例行基因检查,20例（76.9%）存在NIPBL基因变异,3例（11.5%）HDAC8基因变异,1例（3.8%）SCM1A基因变异,2例未发现与临床吻合的致病性基因变异,表型各异。结论 CdLS患儿存在特殊外貌、生长发育迟缓、多器官受累、听力障碍,多数可通过典型临床表型诊断,基因检测有助于非典型患者的早期诊断。

背景 X-连锁隐性遗传点状软骨发育不良(CDPX1)是一种罕见的先天性骨骼和软骨发育障碍性疾病,致病基因为ARSE基因.目前国内报道较少,且均为新生儿,尚无儿童患者表型报道.目的 分析ARSE基因突变致CDPX1的临床表型和基因型.方法 收集郑州大学第三附属医院2018年6月确诊的1例ARSE基因突变致CDPX1患者的临床资料,对其临床特征及全外显子测序结果 进行分析,并以"点状软骨发育不良""芳香基硫酸酯酶E"和"chondrodysplasia punctate""ARSE"为检索词,分别在中国知网、万方数据知识服务平台、PubMed以及人类基因组突变数据库(HGMD)检索建库至2020年2月的相关文献,总结ARSE基因突变致CDPX1患者的临床表型和基因型.结果 本例患儿,男性,胎儿超声发现鼻梁低平,出生后呼吸困难,混合性耳聋,鼻发育不良,四肢短,手指短,认知及运动发育落后,房间隔缺损,X线检查示有典型的点状钙化.全外显子测序结果 发现ARSE基因c.1219G>A(p.E407k)半合子变异,患儿父亲与姐姐该位点为野生型,患儿母亲为杂合突变,该变异国内外未见文献报道.经数据库检索到ARSE基因突变致CDPX1且有详细临床表型的病例23例,其中男22例,女1例,胎儿期确诊4例,其中2例活产,1例26周流产,1例不详;1例因出现新生儿期合并弥散性血管内凝血(DIC)死亡.临床表现:面中部发育不良,远端指骨短,脊柱及四肢长骨等点状骨骺,呼吸功能不全,听力异常,脊柱弯曲或椎体形态异常,鼻孔狭窄或闭锁,矮小,先天性心脏病,认知障碍,颈部短,气管及支气管钙化,气道狭窄,喉软骨钙化,肌张力低下,并趾畸形,体质量增长缓慢,喂养困难,宫内生长受限,小于胎龄儿,白内障,胸廓小,椎管狭窄,关节挛缩.其中胎儿期表现:面部扁平,不同程度的鼻发育不良,鼻梁凹陷,脊柱弯曲异常,椎体异常,椎管狭窄,上肢短,骨骺及脊柱弥漫性点状钙化,长骨发育不良,胎儿生长受限.通过HGMD检索到47个ARSE基因突变,包括点突变、单个或多个外显子缺失、完全缺失、染色体易位.结论 首次报道ARSE基因c.1219G>A变异所致CDPX1,扩大了ARSE基因的突变谱,且报道了患者从胎儿期到2岁的临床表型,有助于对CDPX1临床表型及基因型的认识.

This is a retrospective study done on 170 children, aged 3 to 5 years, who were delivered in the third affiliated hospital of Zhengzhou university, Henan, China between Jan 2019 to Dec 2020. With the help of hospital records, a systematic detection of hypoglycemia (<2.2 mmol/L or 40 mg/dL) was carried out in the study population from birth to 28 days after birth. Main outcomes were a compiled neurological or neurodevelopmental outcome; any developmental delay; motor developmental delay; and cognitive developmental delay. For analysis, the study population was divided into two groups: one group consisted of children who suffered from 5 or more episodes of hypoglycemia in neonatal period (n=42) and the second group consisted those who suffered with less than 5 episodes (n=128). We noted that the group having 5 or more hypoglycemic episodes had a higher proportion of premature or small for date children than the other group (76.2% Vs 60.9%), and the difference is statistically significant. In adjusted regression analyses, the odds ratio (OR) of any neurological or neurodevelopmental outcome was 1.48 (95% confidence interval: 1.17–1.88) in group with 5 or more hypoglycemic episodes as compared to the other group. The adjusted risk of any developmental delay was more than doubled (OR 2.53 [1.71–3.73]), the adjusted risk of motor developmental delay was almost doubled (OR: 1.91 [1.06–3.44]) and the adjusted risk of cognitive developmental delay was almost tripled (OR 2.85 [1.70–4.76]) in the group that had more than 5 hypoglycemic episodes in neonatal period.