Objective:To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection.Methods:A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study.Results:The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months.Conclusions:MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Objective:To construct a clinical prediction scale for focal cortical dysplasia (FCD)type Ⅱ in the malformation of cortical development (MCD) disease spectrum in children.Methods:A case-sectional study.From January 2014 to June 2019, patients who underwent surgery at the Pediatric Epilepsy Center of Peking University First Hospital and were pathologically diagnosed with MCD after surgery were enrolled and randomly divided into the training set and the validation set using random numbering.Clinical, electrophysiological, and imaging data of patients in the training set were analyzed.Variables that could predict FCD type Ⅱ were screened out using a Logistic regression model, and a rating scale was constructed.The diagnostic efficiency of the scale was validated in the validation set to determine the optimum cut-off value, and a consistency test was performed.Results:A total of 381 patients were enrolled in the study, with 260 in the training set and 121 in the validation set.Five clinical factors that exhibited a significant correlation with FCD type Ⅱ were identified in the training set through the logistic regression model: (1) age of seizure onset (<24 months); (2) lesion involving the frontal lobe; (3) epileptic spasms; (4) family history of epilepsy; (5) hippocampal atrophy ± signal change.Based on these 5 variables, the FCD type Ⅱ prediction scale was developed and validated in the validation set with an area under the curve of 0.732.The optimum cut-off value for the prediction scale was 1, at which point the Youden index was 0.384.The scale′s positive predictive value was 0.836, and the negative predictive value was 0.500.The diagnostic consistency between the pathological diagnosis and the FCD type Ⅱ prediction scale was acceptable (Kappa value=0.351), and there was no statistically significant difference between the two diagnostic methods ( P value of the McNemar test=0.065). Conclusions:The FCD type Ⅱ prediction scale has clinical practicability.The application of this scale to predict the pathological type of MCD before operation can help doctors choose the appropriate surgical strategy.

Objective:To evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis (MG).Methods:Case series study. The clinical manifestations, laboratory tests, treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children′s Medical Center of Peking University First Hospital were retrospectively collected.Results:There were 5 males and 22 females in 27 MG children. The onset age was 2.1 (1.6, 4.8) years, ranging from 8 months to 11 years. The clinical classification included 20 children (74%) of ocular MG and 7 children (26%) of generalized MG. Seventeen children (63%) had positive MG-related pathogenic antibodies, including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody. Rituximab was used as first-line immunosuppressant in 13 children, second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child. Immunosuppressants used before rituximab including 8 children of cyclosporine, 3 children of tacrolimus, 1 child of azathioprine, 1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine. Rituximab was used for at least half a year with a follow-up period of more than 12 months. At the last follow-up after rituximab treatment, all children achieved improved or above, 14 children (52%) achieved complete stable remission, 7 children (26%) achieved pharmacologic remission, 1 child (4%) achieved minimal manifestations, and 5 children (18%) improved. After rituximab treatment, 27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy, and 22 children (81%) had stopped the glucocorticoid therapy. Among the 14 children with poor efficacy of other immunosuppressants, rituximab had complete stable remission of 7 children. The most common adverse reaction was respiratory infection (4 children (15%)). Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment.Conclusions:Rituximab has good efficacy and tolerance in pediatric MG. Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.

Objective To investigate the electrophysiological characteristics of hamster primary cortical neurons by using the whole-cell patch-clamp recordings in a Mg2+-free cell model of epilepsy.Methods The cerebral cortex were isolated for primary neuron culture from neonatal Syrian hamsters 1-2 days after birth.After 12 days,primary neurons were exposed to normal external(Mg2+group)or Mg2+-free external(Mg2+-free group)respectively for 3 hours,followed by a 24-hour incubation in normal culture medium.Excitatory postsynaptic currents(EPSC)and excitatory postsynaptic potentials(EPSP)were recorded in voltage clamp mode and current clamp mode using whole-cell patch-clamp recordings,respectively.Results Compared to Mg2+group,the frequency of EPSC[(124.38±75.15)Hz vs.(33.93±22.32)Hz,P<0.001](P<0.001)and EPSP[(37.05±38.37)Hz vs.(5.63±9.52)Hz,P<0.01]in primary cortical neurons from the Mg2+-free group increased significantly.Meanwhile,there were no statistically significant differences in the amplitude,area under the curve and half-width of EPSC and EPSP between the two groups(P>0.05).Conclusion The present study demonstrates an increase in excitability of primary hamsters cortical neurons after Mg2+depletion,suggesting that these neurons can be utilized to use to create cell models of epilepsy.

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.

Objective:To illustrate the onset of epileptic seizures in children with brain injury admitted in pediatric intensive care unit (PICU), and to explore the risk factors and the correlation between epileptic seizures and the prognosis.Methods:Clinical data of pediatric patients with brain injury who were admitted to PICU of Peking University First Hospital from January 2013 to December 2019, and monitored by video electroencephalography (VEEG) were retrospectively collected, including general demographic information, etiological data, clinical seizures prior to VEEG performing, in-hospital mortality, brain function score, VEEG manifestations, etc.Seizures detected by VEEG were the primary outcome, and prognosis when discharged from PICU was the secondary outcome. Logistic regression was used to analyze the factors associated with seizures and poor outcome. Results:A total of 284 children were included, involving 54.9%(156/284) males.The median age of included children was 1.7(0.5, 5.0) years.Stratified by the cause of disease, 45.1%(128/284) had epilepsy, 26.1%(74/128) had genetic metabolic disease, and 14.4%(41/284) had central nervous system infection.A total of 82.0%(233/284) children had abnormal VEEG background activities, and 59.5%(169/284) had interictal epileptic discharges.Seizures were detected in 106 cases, including 39.6%(42/106) of non-convulsive seizures and 24.5%(26/106) of non-convulsive epileptic states.There were 12.0% (34/284) had poor prognosis at discharge, including 24 patients died in-hospital, and Pediatric Cerebral Performance Category scores were increased in 10 survivors.Multivariate Logistic regression analysis showed that seizures existed before VEEG monitoring and interictal epileptiform discharge were the independent risk factors for seizure.Besides, mental retardation, sepsis related encephalopathy, consciousness abnormality during VEEG, abnormal VEEG background activity, and epileptic status were significantly correlated with the poor prognosis of children with brain injury in PICU. Conclusions:The incidence of electrographic seizure is higher in children with brain injury in PICU, and VEEG monitoring is beneficial to children with brain injury that achieves an early identification of seizures and prediction of prognosis.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.