1.Sialidosis: a case report
Taoyun JI ; Yao ZHANG ; Yuehua ZHANG ; Xinhua BAO
Journal of Clinical Pediatrics 2017;35(7):529-531
Objective To explore the clinical features and pathogenic genes of sialidosis. Methods The clinical data and genetic test results of a family with sialidosis were retrospectively analysed. Results The proband was a 13-year-old girl who presented with limb pain at age 7, followed by progressive vision loss and convulsive seizure. In addition, she also had the sign of ataxia. Fundus examination showed optic atrophy in her eyes. Visual evoked potential showed that the latency of binocular P100 was significantly prolonged. The elder brother of the proband showed similar manifestation. PCR was used to amplify the exons and exon-intron boundaries of the NEU1 gene, and DNA direct sequencing was used to detect the mutation in this gene. It was found that both proband and her brother carried two known pathogenic heterozygous mutations in the NEU1 gene, c.239C>T (p.P80L) and c.544A>G (p.P80L) respectively from both their mother and father of normal phenotype. Conclusion The causative mutation of the NEU1 gene in the family of sialidosis has been defined.
2. Early diagnosis of autoimmune encephalitis
Chinese Journal of Applied Clinical Pediatrics 2019;34(24):1851-1854
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.
3. A case report of childhood Farber′s disease and literature review
Xinhua BAO ; Jiamei TIAN ; Taoyun JI ; Xingzhi CHANG
Chinese Journal of Pediatrics 2017;55(1):54-58
Objective:
To explore the clinical features, diagnosis, treatment and the prognosis of Farber disease by case report and literature review.
Method:
The clinical information of a case with farber′s disease diagnosed in October 2015 at Peking University First Hospital was collected and analyzed, including clinical manifestation, electrophysiology, magnetic resonance imaging, pathology, treatments and prognosis.ASAH1 gene mutational analysis was conducted in the patient and her parents.By using "Farber′s disease, ASAH1" as keywords, literature was searched from Pubmed, CHKD and HGMD database from January 1951 to January 2016.
Result:
The girl, 2 years 2 months old, was sent to our hospital in October 2015, with complains of "joint swelling for 17 months, development regress of intelligence and movement for 11 months, intermittent seizures for 2 months" .The clinical manifestation of the patient was characterized by painful and deformed joints, subcutaneous nodules, progressive hoarseness, and the progressive neurological system deterioration.Joints swelling and deformity behave as the first symptoms.A series of electroencephalogram showed slow background and spike wave.Visual evoked potential was significantly abnormal.Brain magnetic resonance imaging (MRI) showed hypomyelination and progressive diffuse brain atrophy.Histology of subcutaneous nodule showed proliferation of the connective tissue with hyalinization, cholesterol crystal like changes, and a large number of foamy cell infiltration.Compound heterozygous mutations of ASAH1 gene, c. 304_305 ins A (p.T102Nfs14) and c. 314T>C (p.L105p), were found in the patient, and the former is inherited from her mother, the latter from her father.Antiepileptic treatment and other symptomatic treatments were delivered to the patient, but the effectiveness was poor.One reference from China hownet and 35 references from Pubmed have reported a total of 26 cases.Twenty out of 26 patients (77%) had the onset under 1 year of age.By region, there were 12 patients (12/26, 46%) from India, and the others around world.Among these 12 indian patients, 10 lack of complete clinical data.Among the rest 16 patients, 4 patients′ parents were consanguineous; 8 patients with the main clinical manifestation of painful and deformed joints, subcutaneous nodules, and hoarse cry; 4 patients with hepatic failure and impaired spleen; 5 patients with rapid neurological deterioration; 1 patient with bone destruction; 7 patients under liver and skin biopsies, pathologically showing a large number of foam cells and "Farber bodies" . There are 33 genetic mutations, and 45% (15/33) mutations are concentrated in ASAH1 exon 6-10.
Conclusion
Farber disease is a rare autosomal recessive disease caused by deficiency of lysosomal acid ceramidase.Histopathology of granulomatous tissue plays an important role in the early diagnosis.
4.Intellectual disability, macrocephaly and seizures caused by de novo variants in PAK1: a case report
Zimeng GUO ; Rong ZHAO ; Taoyun JI
Chinese Journal of Applied Clinical Pediatrics 2023;38(7):546-549
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.
5.Anti-N-methyl-D-aspartate receptor encephalitis with demyelinated lesions in 3 children and literature review
Ji ZHOU ; Yao ZHANG ; Taoyun JI ; Yuehua ZHANG ; Hui XIONG ; Xinhua BAO ; Ye WU
Chinese Journal of Applied Clinical Pediatrics 2017;32(24):1887-1891
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.
6. Effectiveness and safety of rituximab for children with autoimmune diseases of the nervous system
Zhuo FU ; Xinhua BAO ; Ye WU ; Ji ZHOU ; Yuehua ZHANG ; Yao ZHANG ; Taoyun JI ; Yan CHEN
Chinese Journal of Pediatrics 2017;55(9):689-694
Objective:
To assess the effectiveness and safety of rituximab in Chinese children with autoimmune diseases of the nervous system.
Method:
An ambispective cohort study enrolled patients with refractory and(or) relapse autoimmune diseases of nervous system from June 2010 to June 2016 in Peking University First Hospital.These patients failed to respond to steroids and(or)intravenous immunoglobulin (IVIG) were treated with rituximab and seen for follow-up visits once every 3 months.The effectiveness was assessed by modified Rankin scale (mRs) and the annualized relapse rate.B cell was repeatedly counted after the treatment.Side effects attributed to rituximab were recorded.Paired rank test and chi-square test were used to compare the mRs score and the recurrence rate (time/year) before and after the treatment.
Result:
A total of 38 patients (15 males and 23 females) with mean age of (6±4) years were treated with rituximab.Among those patients, 4 cases were in multiple sclerosis, 5 in neuromyelitis optica, 6 in opsoclonus myoclonus syndrome, 9 in myasthenia gravis, and 14 in autoimmune encephalitis and other nervous system autoimmune diseases.The course of the disease before rituximab treatment was from two months to 7.25 years, with the average of (21±19) months.The patients had been followed up for 2-52 months. The mRs score and recurrence rate of 38 patients before receiving rituximab was 3 points (3, 4) and 2.56 (1.80, 4.75) times per year, respectively, while patients after receiving rituximab were mRs score of 0 (0, 2) and had a recurrence rate of 0 (0, 0.17) per year.There was statistical difference before and after treatment (
7. Clinical analysis of neuromyelitis optica spectrum disorders in childhood
Ji ZHOU ; Yao ZHANG ; Taoyun JI ; Yiwen JIN ; Xinhua BAO ; Yuehua ZHANG ; Hui XIONG ; Xingzhi CHANG ; Yuwu JIANG ; Ye WU
Chinese Journal of Pediatrics 2019;57(2):118-124
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
8.Electroencephalographic features of anti-N-methyl-D-aspartate receptor encephalitis in children.
Xin GAO ; Zhixian YANG ; Jiao XUE ; Taoyun JI ; Yao ZHANG ; Xiaoyan LIU ; Ye WU ; Yuehua ZHANG ; Xinhua BAO ; Yuwn JIANG
Chinese Journal of Pediatrics 2016;54(3):192-196
OBJECTIVETo investigate electroencephalographic (EEG) characteristics of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis in children.
METHODClinical data of 28 children diagnosed as anti-NMDAR encephalitis were retrospectively analyzed for EEG characteristics in different periods and severity of disease and outcome.
RESULTAmong the 28 patients with anti-NMDAR encephalitis, 15 were males and 13 were females. Their age at disease onset ranged from 1 year 3 months to 12 years 4 months. Patients were divided into mild group (5 cases) and severe group (23 cases). In the different stage of the disease, occipital background activity of the EEG was preserved in more than half of patients. Accompanied by the evolution of disease course, the occipital background activity and slow waves gradually recovered to normal. In the peak phase of disease, occipital background activity in the awake state was preserved in 4/5 patients of the mild group and 9/17 patients of the severe group. Alpha and theta band rhythms in non-rapid eye movement (NREM) sleep existed in 77% (17/22) patients. EEG monitoring showed delta brushes in 2 cases, and the delta brushes were mixed with background fast waves in one case; 71% (20/28) patients had epileptiform discharges in EEG during the course, and among them, 6 patients had secondary epilepsy.
CONCLUSIONThe background activity in the awake state and abnormal diffuse slow waves of EEG were evolved and gradually recovered during the course of the disease. Regardless milder or severe illness condition, occipital background activity was still preserved during different stages in most patients. Alpha and theta rhythms in NREM sleep might represent a relatively overt EEG characteristic. The presence of delta brush in EEG was rare, and sometimes they were difficult to be distinguished from fast wave activities caused by drugs. The presence of epileptiform discharges in EEG suggested the possibility of secondary epilepsy.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; Child ; Electroencephalography ; Female ; Humans ; Male ; Receptors, N-Methyl-D-Aspartate ; Retrospective Studies ; Sleep
9.Analysis of surgical prognosis and related prognostic factors of drug-refractory epileptic spasms of focal onset
Taoyun JI ; Ruofan WANG ; Qingzhu LIU ; Shuang WANG ; Hao YU ; Wen WANG ; Guojing YU ; Lixin CAI ; Yuwu JIANG ; Xiaoyan LIU ; Ye WU
Chinese Journal of Applied Clinical Pediatrics 2021;36(17):1333-1337
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.
10.Surgical treatment of epilepsy in children with definite epileptogenic lesion under 1 year old
Hao YU ; Lixin CAI ; Qingzhu LIU ; Chang LIU ; Yu SUN ; Xiaoyan LIU ; Shuang WANG ; Taoyun JI ; Ruofan WANG ; Yuwu JIANG
Chinese Journal of Applied Clinical Pediatrics 2020;35(14):1081-1084
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.