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.

The clinical data of a child with intellectual disability, macrocephaly and seizures associated with de novo variants in the PAK1 gene who was treated in the Department of Pediatrics, Peking University First Hospital in March 2022 were retrospectively analyzed.Meanwhile, literature review was performed to analyze the pathogenicity and mutation characteristics of the PAK1 gene.A boy with 4 years and 8 months old presented clinical manifestations of intellectual disability dominated by speech impairment and recurrent epilepsy.The patient had special facial features, including large head circumference, long face and low nose beam.Video electroencephalogram showed slow waves in the bilateral anterior head regions, and sharp wave, spike-slow complex waves and sharp-slow complex waves in the left hemisphere.Head magnetic resonance imaging revealed enlargement of the bilateral cerebral gyri, cerebellum and brainstem, thickening of cortex and corpus callosum, and enrichment of white matter.A de novo heterozygous mutation c. 361C>A(p.Pro121Thr ) was found in exon 4 of PAK1 (NM_001128620). This article for the first time reported a case of intellectual disability, macrocephaly and seizures caused by the de novo variants in the PAK1 gene in China.The pathogenic gene in this family was identified, which provided the possibility for accurate genetic counseling.

Objective:To summarize and investigate the clinical characters of epilepsy in children with Mowat-Wilson syndrome (MWS), thus to improve the understanding of this disease.Methods:Clinical characters of epilepsy episodes in 5 children with MWS admitted to Department of Pediatrics, Peking University First Hospital from June to December 2020 were retrospectively reviewed. Clinical data including onset age of seizures, clinical features, characters of electroencephalogram (EEG), magnetic resonance imaging (MRI) findings, results of ZEB2 gene testing and responses to the anti-seizure medications (ASM) were summarized.Results:The onset age of seizures in the 5 patients (3 males and 2 females) ranged from 6 months to 4 years. Four patients showed focal motor seizures with diverse expressions, while the other 1 patient had epileptic spasms. All the 5 patients showed distinctive face, different degrees of intellectual disability, development delay and other congenital malformations. EEG of 4 patients presented the slowing of background rhythm and epileptiform discharges mainly occurred in the posterior region of the brain. The other 1 patient showed hypsarrhythmia at the beginning of the disease, changing into multifocal discharges mainly occurred in posterior region later. Corpus callosum abnormality and white matter disability were found from investigations of MRI in 2 patients, respectively. All the 5 patients carried a de novo heterozygous variation in the ZEB2 gene, 4 were nonsense variants and 1 was frame-shift variant. Within the follow-up of 14 months to 20 months, 3 patients achieved seizure-free more than 1 year, 2 patients achieved seizure-free more than 6 months. Two patients used valproate only and 2 patients received valproate combined with other ASM. Conclusions:Epileptic seizures are common clinical phenotype of MWS. Focal motor seizure may be the most common seizure type and epileptic spasms exist. The manifestations of EEG can be age-related. The most common type of variation of the ZEB2 gene is de novo nonsense variation. Valproate might be the first-line ASM for patients with MWS.

Objective:To explore the clinical manifestations and surgical outcomes of pediatric epilepsy patients with epileptic spasms (ES) as the main form of seizure, so as to analyze the correlative factors with prognosis and improve the understanding of the operation and preoperative positioning for such patients.Methods:The clinical data of patients with ES who underwent surgery therapy from June 2014 to December 2015 in Pediatric Epilepsy Center, Peking University First Hospital were collected and retrospectively analyzed.Demographic characteristics, seizure forms, etiology, electroencephalogram (EEG), cranial magnetic resonance imaging (MRI), operative methods, pathological findings as well as surgical outcomes evaluated by Engel classification during follow-up of the subjects were collected.Correlative factors with the prognosis were explored by comparing the data between patients with optimal outcome (Engel Ⅰ) and those with poor outcomes (Engel Ⅱ-Ⅳ).Results:A total of 25 pediatric patients were enrolled, including 16 males (64.0%) and 9 females (36.0%). The age of onset was (0.81±0.68) years, the age at operation was (2.98±1.63) years, and the course of disease was (2.17±1.48) years.Besides, 84.0% (21/25 cases) of the ES patients had multiple forms of seizures and partial seizure (19 cases) was the most common.MRI of the heads of all the children showed definite lesions, including 11 patients (44.0%) with lesions limited to one brain lobe and 14 patients (56.0%) involving multiple brain lobes or hemisphere.The most common etiology was focal cortical dysplasia (13 cases), followed by intracranial developmental tumors (3 cases). All patients underwent resection surgery, including resection of lesion (3 cases), single brain lobe resection (9 cases), multiple brain lobe dissection (3 cases) and hemisphere dissection (10 cases). During a follow-up period of 4.0 to 5.5 years, 1 patient was lost.Among the remaining 24 cases, 18 (75.0%) cases achieved good outcomes and wee classified as EngelⅠ, 2 cases (8.3%) and 4 cases(16.7%) were classified as Engel Ⅱand Ⅳ, respectively.The univariate comparison between the good epilepsy prognosis group and the poor epilepsy prognosis group showed that, patients whose EEG abnormalities are consistent with the anatomical lesions during the inter ictal tend to have good prognosis( P=0.006). Conclusions:(1) Optimal therapeutic effects were observed in ES patients with definite lesions treated by surgical therapy.(2) Interictal EEG consistent with the lesion side may suggest a good prognosis for surgical treatment.(3) Structural causes should be screened as soon as possible if a patient with ES is drug-refractory and presents clues of focal origin.

Objective:To investigate the clinical characteristics, surgical methods, complications and prognosis of children younger than 1 year old who had definite epileptogenic lesions under 1 year old.Methods:A total of 14 children with definite epileptogenic lesions and underwent radical surgery in Pediatric Epilepsy Center of Peking University First Hospital from March 2017 to July 2019 were selected.Their clinical data including operation age, course of disease, etiology, physical examinations, seizure types, seizure frequency, features of interictal electrocorticography(EEG), surgical methods, antiepileptic drugs, and pathology were collected and analyzed.Postoperative efficacy was eva-luated using Engel grading.The Griffiths neurodevelopmental scale and the Peabody motor developmental scale were used to assess motor neurodevelopment.Results:The operation age of 14 children was 119 to 358 days (median: 281 days), and the course of disease ranged from 119 to 352 days (median: 266 days). The age of onset was from 0 to 135 days was (median: 7.5 days), and the postoperative follow-up time was 0.5-2.0 years(median: 1.5 years). None of the patients had seizure recurrence at the last follow-up.During the follow-up period, 1 patient had recurrence, but deve-loped no seizures anymore after drug administration.Cognitive and motor functions improved during follow-up in all children.All the children had no serious complications such as postoperative infection and hydrocephalus.Conclusions:Young children with definite epileptogenic lesions have an early onset of seizures, which has a great influence on development.Multidisciplinary preoperative evaluation shows that surgery is a safe way to terminate progression of seizures, thus helping children to well develop and reducing the use of antiepileptic drugs.

Autoimmune encephalitis is a group of treatable autoimmune diseases of central nervous system.Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitis.Some of autoimmune encephalitis can be confirmed by specific autoantibodies, but excessive dependence on autoantibody detection usually leads to delayed treatment.This article reviews the clinical presentations of pediatric anti-NMDAR encephalitis and the antibody-negative autoimmune encephalitis so as to improve the pediatricians understanding on the diseases.

Objective: To explore clinical features and the effect of treatment of neuromyelitis optica spectrum disorders (NMOSD) in childhood. Methods: Children who were hospitalized in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2018 and meeting diagnostic criteria of NMOSD proposed by the International Panel for NMOSD Diagnosis in 2015 were summarized and followed up. The basic information, symptoms of each attack, locations and patterns of new lesions, features of cerebrospinal fluid, serologic markers, treatments and outcomes in these patients were analyzed. Thirty-three children were included in the study, with 13 males and 20 females. The median age of onset was 6.83 (4.25, 8.75) years. Compared aquaporin-4 immunoglobulin G (AQP4-IgG) associated NMOSD with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated NMOSD. Mann-Whitney U test was used for continuous variables and Fisher test for categorical variables in comparison between AQP4-IgG and MOG-IgG associated NMOSD. Wilcoxon test was used for annualized relapse rate (ARR) before and after adding disease-modifying drugs. Results: Optic neuritis (39% (13/33) in initial attacks and 49% (62/127) in total attacks) and myelitis (36% (12/33) in initial attacks and 26% (33/127) in total attacks) were the top two symptoms in both the initial attacks and all 127 attacks during follow-up. There was 42% (37/89) of brain magnetic resonance imaging (MRI) scans in acute phase showing new lesions in supratentorial white matter, with 43% (16/37) showing acute disseminated encepha lomyelitis (ADEM)-like or leukodystrophy-like patterns. AQP4-IgG was detected in 30% (10/33) patients, and MOG-IgG was detected in 55% (11/20) patients, with no combined positive case. In 20 patients treated with rituximab, two were treated after the initial attack. In the other 18 patients, the median annualized relapse rate decreased from 1.86 (1.52, 2.60) before treatment to 0.28 (0, 1.13) during treatment (Z=-3.376, P=0.001). Compared with AQP4-IgG associated NMOSD (10 cases), fever of unknown origin (8/40 vs. 0/33, P=0.007) was more common, area postrema syndrome (0/40 vs. 4/33, P=0.038) was fewer, cell count of cerebrospinal fluid (49.0 (17.5, 115.0) ×10⁶/L vs. 5.5 (3.0, 15.8)×10⁶/L, Z=-3.526, P=0.000) was higher in MOG-IgG associated NMOSD (11 cases). Conclusions In childhood-onset NMOSD, optic neuritis and myelitis were top two symptoms. Childhood-onset NMOSD has high proportion of positive MOG-IgG. Lesions in supratentorial white matter are common. Rituximab could significantly decrease ARR of NMOSD in childhood. However, more studies should be conducted to explore the optimal treatment strategy in different antibody associated NMOSD.

Objective To identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy (PME).Methods In this cross-sectional study,26 PME children (11 boys and 15 girls) sent to neurological outpatient clinics and admitted to wards of the Department of Pediatrics,Peking University First Hospital were enrolled prospectively from January 2014 to October 2018.The pathogenic gene variants of PME children and their parents were identified by Sanger sequencing,next generation sequencing panels of epilepsy or trio-based whole exome sequencing and so on.The genotypes and phenotypes of the PME children were anaylzed.Results The clinical features of 26 children include myoclonus,multiple types of seizures and progressive neurological regression.Their onset ages ranged from 3 months to 15 years.Several pathogenic gene variants were identified in the 15 patients,including TPP1 gene variantions in 3 patients;NEU1,GBA,TBC1D24 and KCNC1 gene variantions in 2 patients respectively;CLN6,MFSD8,ASAH1 and ATN1 gene variantions in 1 patient respectively.Several variants of uncertain significance were identified in 4 patients,including GOSR2 gene compound heterozygous variants in 2 patients,KCTD7 gene compound heterozygous variants in 1 patient,and compound heterozygous variants of an unreported TARS gene in 1 patient.No pathogenic gene variant was identified in 7 patients.In 15 children with the identified pathogenic gene variants,5 patients were diagnosed with neuronal ceroid lipofuscinoses (NCL),2 patients with sialidosis,2 patients with neuronopathic Gaucher disease,1 patient with dentatorubral-pallidoluysian atrophy (DRPLA),and 1 patient with spinal muscular atrophy-progressive myoclonic epilepsy (SMA-PME).Conclusions PME include a group of diseases with genetic heterogeneity.Identification of the pathogenic gene variants of PME could help to predict the prognosis and guide the genetic counseling.

Objective To study the predictive value of magnetic resonance imaging (MRI),positron emission computed tomography (PET)and PET/MRI coregistration in intractable epilepsy of children.Methods A retrospec-tively analysis was performed based on the surgery data at the Department of Children Epilepsy Center of Peking Univer-sity First Hospital from September 2015 to March 2016.The clinical data,surgery and follow－up study data,interictal and ictal electroencephalogram,MRI,PET and PET/MRI coregistration data were collected.By comparison with the epi-leptogenic zone designed by pre－surgical workup,the accuracy of MRI,PET and PET/MRI coregistration in detecting lesion was assessed.In the patients who had no seizure during≥1 year follow－up,their sensitivity,specificity,positive predictive value,negative predictive value of MRI,PET and PET/MRI coregistration were calculated.Results (1)A total of 62 patients underwent surgery,30 boys and 32 girls. The average age on epilepsy onset was 2. 50 years (2 days－11.70 years),and average age on surgery was 5.10 years old(0.75－15.60 years old).(2)Surgical treat-ment of 62 cases included the resection of the focal or lobar (32 cases,51.6%),and the multilobar (16 cases, 25. 8%).Hemispherotomy was done in 14 cases (22.6%).During ≥1 year follow－up,seizure outcome was Engel class Ⅰ in 57 cases (91.9%)out of the 62 patients,Engel classⅡto Engel classⅣin 1 case,3 cases,and 1 case, respectively.(3)Referred to epileptogenic zone designed by presurgical workup,MRI represented 64.5%(40/62 ca-ses)results with accordance,PET and PET/MRI coregistration was 72.5%(45/62 cases)and 85.5%(53/62 cases), respectively,and the difference was significant(χ2＝7.25,P＝0.03).(4)Based on the patients of Engel class Ⅰ, their sensitivity and specificity were 66.7%,60.0% in MRI,75.4%,60.0% in PET %,and 85.9%,80.0% in PET/MRI coregistration,respectively.(5)There were 11 ＂non－lesion＂ cases of all focal cortical dysplasia in patholo-gy,and subtle structural abnormalities were de tected in 9 cases by reviewing MRI.Conclusions PET/MRI coregistra-tion can improve lesion detection of intractable epilepsy in children.

Objective To summarize the clinical and prognostic features of anti - N - methyl - D - aspartate receptor (NMDAR)encephalitis with demyelinated lesions and discuss the possible pathogenesis. Methods The clini-cal and imaging features of 3 pediatric patients diagnosed as anti - NMDAR encephalitis with demyelinated lesions were analyzed. The published papers were browsed by using " anti - NMDA receptor encephalitis" and " demyelinating"as key words into CNKI,Wanfang and PubMed database from starting point to May,2017. Results In 3 cases,anti -NMDAR encephalitis occurred simultaneously with demyelinated episodes in 2 cases,successively in the other case. One case had AQP4 - IgG positive. Two cases had recurrent course,and 1 case had a single course and poor prognosis. A to-tal of 15 articles reported 41 cases,including 16 (39. 02％)pediatric cases. In these pediatric cases,anti - NMDAR encephalitis occurred in 7 cases (43. 75％)successively and demyelinated episodes occurred in 9 cases (56. 25％) simultaneously. AQP4 antibody and MOG antibody in serum and/ or cerebrospinal fluid were detected in all cases,with either of two antibodies positive in 9 cases (56. 25％). Conclusion Anti - NMDAR encephalitis might occur simulta-neously or successively with demyelinated episodes. Compared with typical patients with anti - NMDAR encephalitis, patients with demyelinated lesions are more likely to relapse and have worse outcomes. Anti - NMDAR encephalitis and demyelinated lesions are both based on similar immune dysfunction or demyelinated lesions are also induced by anti -NMDAR antibodies,which is the probable pathogenesis.