Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To evaluate the long-term safety, tolerability and efficacy of Lacosamide add-on therapy in Chinese children with partial-onset seizures.Methods:SP848 was a global multicenter single-arm study involving 60 Chinese children with partial-onset seizures with the age of 4-17 years who were managed by Lacosamide add-on therapy at seven hospitals across China from April 2018 to May 2019.After treatment with at least two kinds of anti-seizure medications simultaneously or sequentially, partial seizures were still poorly controlled and Lacosamide oral solution (syrup) or tablets were added.The minimum initial oral dose was 2 mg/(kg·d), and the maximum allowable dose was 12 mg/(kg·d)or 600 mg/d during the study period.The dose was adjusted according to the tolerance and seizure control level of partial-onset seizures children.Seizure frequency and the median percentage change in partial-onset seizures per 28 days from baseline to the final visit were recorded, including 50% responder rate and 75% responder rate.Results:A total of 60 Chinese children with the mean age of 9.18 (4.00-15.40) years were included in this interim analysis, involving 39 males and 21 females.The mean course of epilepsy was 5.04 (0.50-15.20) years.A total of 43 patients (71.7%) still have been treated.One patient (1.7%) has completed the 6-12 months of follow-up, and 14 patients (23.3%) have completed the follow-up for less than 6 months.The median change in the frequency of partial seizures every 28 days from baseline to the last visit was -2.91, with its median percentage as -25.46%, and the proportions of ≥50%, while ≥75% responder rate were 40.0% and 28.3%, respectively.A total of 52 patients (86.7%) had 265 treatment emergent adverse events (TEAE), 11 patients (18.3%) had 19 serious TEAE, 37 patients (61.7%) had 127 drug-related TEAE, and 11 patients (18.3%) had 16 TEAE leading to the discontinuation of the trial.The most common TEAE were upper respiratory tract infections (20 cases, 33.3%), followed by drowsiness (16 cases, 26.7%), dizziness (15 cases, 25.0%) and vomiting (13 cases, 21.7%). There were no abnormal changes in the electrocardiographic findings during the treatment.Conclusions:For Chinese patients with partial seizures who are older than the age of 4 years and poorly controlled by other drugs, Lacosamide is effective and well tolerated as an add-on therapy drug.The safety characteristics are consistent with those reported in children and adults.No new safety concerns are identified.

Ketogenic diet(KD)is a formulation diet with a high proportion of fat, low proportion of carbohydrates, appropriate protein and other nutrients, which has been used for centuries in the treatment of refractory epilepsy.In recent years, KD has been shown to be effective in the treatment of other diseases, such as amyotrophic lateral sclerosis, traumatic brain injury, diabetes, obesity, etc.Although KD has a positive effect on the treatment of a variety of diseases, the short-term and long-term adverse reactions caused by the imbalance of its nutritional structure should not be ignored.This article reviews the adverse reactions of KD in the treatment of children with refractory epilepsy and the corresponding prevention and treatment measures, to guide safe and efficient implementation of KD therapy in the clinic.

OBJECTIVE To explore the effects of Chaihu xianxiong decoction containing serum on human umbilical vein endothelial cells ECV 304 injury induced by high -fat serum and its mechanism . METHODS The high -fat serum and Chaihu xianxiong decoction containing serum were prepared . ECV304 injury was induced by high -fat serum ，and the intervention experiments were conducted with low -concentration，medium-concentration and high -concentration（3.47，6.94，13.88 g/kg，by crude drug ）of Chaihu xianxiong decoction containing serum . The proliferation rate ，the levels of related inflammatory factors [tumor necrosis factor -α（TNF-α），interleukin-6（IL-6）] and vascular endothelial function indexes [endothelial nitric oxide synthase （eNOS），nitric oxide （NO）and endothelin -1（ET-1）] were all detected in each group . mRNA expressions of intercellular adhesion molecule-1（ICAM-1）and transforming growth factor -β1（TGF-β1）were detected ，and the expression of Toll -like receptor 4 （TLR4），nuclear factor -κB inhibitor α（IκBα），phosphorylated I κBα（p-IκBα）protein and the ratio of phosphorylated nuclear factor-κB p 65（p-NF-κB p 65）to NF -κB p 65 were also detected . RESULTS Compared with control group ，the proliferation rate of cell，the levels of TNF -α，IL-6 and ET -1，mRNA expression of ICAM -1，protein expressions of TLR 4 and p -IκBα and p -NF-κB p65/NF-κB p 65 ratio were significantly increased in the model group （P＜0.05）；the levels of eNOS and NO ，mRNA expression of TGF-β1 and protein expression of I κBα were significantly decreased （P＜0.05）. Compared with model group ，above indexes were all reversed significantly in low -concentration，medium-concentration and high-concentration groups of Chaihu xianxiong decoction （P＜0.05）， while the Chaihu xianxiong decoction high concentration group were all better than low -concentration and medium-concentration groups （P＜0.05）. CONCLUSIONS Chaihu xianxiong decoction can improve endothelial cell injury induced by high -fat serum . Its mechanism of action may be associated with reducing the levels of inflammatory factors and inhibiting the activation of TLR 4/NF-κB signaling pathway .

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

Objective:To explore clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive myopathy.Methods:Two cases of pediatric anti-HMGCR antibody-positive myopathy admitted to the Department of Neurology, Shenzhen Children′s Hospital from January to July 2020 were retrospectively analyzed for their clinical manifestations, creatine kinase (CK), myositis autoantibody, electromyography (EMG), muscle pathology, muscle magnetic resonance imaging (MRI), and treatment information.Results:Both of them were female cases.Case 1 was 3 years and 11 months old and case 2 was 7 years and 9 months old.They used to be healthy without history of statin use.Case 1 showed chronic onset of the disease, and case 2 had a subacute onset.The main clinical manifestations were progressive symmetric proximal muscle weakness accompanied by myalgia.Case 1 developed skin rash but case 2 did not.Significantly increased CK level was detected in both of them, which increased by 27.3-48.0 and 66.7-77.4 times of the upper limit before treatment in case 1 and case 2, respectively.They were diagnosed as muscular dystrophy at the early stage.EMG results suggested myogenic injuries in 2 cases, and muscle MRI showed extensive muscle edema.The muscle pathology of the 2 cases suggested muscle necrosis with a small amount of inflammatory cell infiltration.After diagnosis, both of them were treated with Methylprednisolone combined with intravenous immunoglobulin.CK decreased significantly but remained high, and muscle weakness was improved but did not return to normal.Oral Prednisone was given after discharge and case 2 was additionally medicated with azathioprine.Conclusions:Compared with adult patients, the clinical characteristics of pediatric anti-HMGCR antibody-positive myopathy are mostly similar.However, children patients usually have no history of statins and are more difficult to treat, less effective and worse prognosis.In addition, children patients are more likely to be diagnosed with " muscular dystrophy" at the beginning of illness.Therefore, idiopathic myositis autoantibody should be examined to confirm the diagnosis for children suspected to be " muscular dystrophy" but not confirmed by genetic examination.

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

The main clinical phenotypes, imaging features and genetic test results of a child with Joubert syndrome treated in Shenzhen Children′s Hospital in July 2020 were analyzed retrospectively, and the literature on Joubert syndrome was summarized.The main manifestations of the protester during infancy were respiratory abnormalities and developmental retardation.The brain magnetic resonance imaging (MRI) showed a " molar sign" , which was consistent with the diagnosis of Joubert syndrome.Genetic testing suggested that the protestor carried complex heterozygous variations of KIAA0586 gene.Two variants were not reported previously, one of which was synonymous mutation.The child is the first case of Joubert syndrome caused by KIAA0586 gene in China.Joubert syndrome is a rare congenital brain development malformation characterized by high clinical heterogeneity and MRI molar signs.It may involve multiple systems.Early identification and intervention can improve outcomes.

Objective:To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation.Methods:The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed.Results:These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions:The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.