ObjectiveWe herein described the clinical characteristics of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) patients with epileptic seizures in the disease course.MethodsA single-center retrospective analysis of autoimmune GFAP-A with seizures was conducted.ResultsThere were 14 patients (35.9%, 14/39) with seizures among 39 pediatric GFAP-A patients, nine were boys and five were girls. Nine patients (64.3%, 9/14) manifested focal seizures, four (28.6%, 4/14) showed generalized tonic–clonic seizures, one (7.1%, 1/14) exhibited both forms, and five (35.7%, 5/14) manifested status epilepticus. In addition to seizures, clinical presentations included fever (71.4%), disorders of consciousness (71.4%), dyskinesia (42.9%), psychiatric symptoms (35.7%), headache (28.6%), and involuntary movements (28.6%). Electroencephalograms were all abnormal during the acute phase, principally presenting as focal or diffuse slow waves. During the acute phase, the control rate of epilepsy with immunotherapy was 50%, and seven patients still needed to be treated with antiseizure medication. After 2 years and 6 months to 4 years and 6 months of follow-up, we observed seven patients (50%, 7/14) with recurrence of seizures at 0.5–15 months after discharge, seven patients were treated with one or more antiseizure medications. Epileptic seizures were ultimately controlled in two patients, seizures diminished in one patient, treatment was ineffective in three patients, and one patient died.ConclusionGFAP-A is an important cause of epileptic seizures in children and immunotherapy plays a crucial role. Several patients experienced chronic epileptic seizures after the acute phase and require long-term antiseizure medication, with a few showing refractory characteristics.

Objective: Serum globulin is associated with inflammatory or immune disorders. However, it has not been established whether it is associated with myasthenia gravis (MG). We investigated the association between globulin with relapse and prognosis in children with MG. Methods: A cohort of 148 MG cases and 150 healthy children were retrospectively enrolled from January 2015 to December 2021. Multivariate logistic and Cox regression models were used to analyze the treatment outcomes and recurrence of case group, exploring the influence of globulin. Results: Compared with the control group, globulin levels in the MG group were slightly increased (t = 7.244, p < 0.001). After a mean follow-up of 2.25 +/- 1.05 years, 35 cases relapsed, with a relapse rate of 23.65%. Logistic regression analysis showed that globulin levels at admission [adjusted odds ratio (OR) = 1.233, 95% confidence interval (CI) 1.028-1.472, p = 0.018] were independent risk factors for relapse. Cox regression analysis confirmed that globulin levels at admission affects relapse-free time [adjusted hazard ratio (HR) = 0.552, 95% CI 0.357-0.852, p = 0.007]. Receiver operating characteristic curve determined 25.10 as the optimal cutoff value for globulin. Cox regression showed that high globulin levels (>25.10) at admission (adjusted HR = 0.607, 95% CI 0.383-0.961, p = 0.033) were independent risk factors for poor therapeutic outcomes at follow-up. Ordinal logistic regression showed that globulin affects the treatment plan (OR = 1.445, 95% CI 1.223-1.847, p = 0.014). Conclusions: Elevated globulin levels in children with MG on admission predicts a high relapse rate and poor long-term therapeutic efficacies.

Objective To examine the clinical characteristics, treatment, and prognosis of recurrent autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Methods The data of 17 pediatric patients with recurrent autoimmune GFAP-A who were treated in the neurology department of Hunan Children’s Hospital from January 2015 to January 2024 were collected, and the clinical presentation, laboratory tests, neuroradiology results, electroencephalograms, treatment regimens, and prognosis of these patients were retrospectively analyzed and summarized. Results These 17 patients included 6 males and 11 females. A total of 28 recurrences occurred, with a median of 1 (1, 2) recurrence per patient. Patients experienced 1–5 symptoms on recurrence, with 3 recurrences exhibiting new symptoms. The median number of symptoms at recurrence was 1 (1, 2), with a median mRS score at recurrence of 3 (2, 4) and a median length of hospitalization of 10 (8, 16) days per recurrence episode. The mean number of symptoms, mRS, and length of hospitalization at recurrence were all lower than at initial disease onset (P < 0.05). The serum GFAP antibody positivity rate was 50% and the cerebrospinal fluid GFAP antibody positivity rate was 14.3% at recurrence. The cerebrospinal fluid abnormality rate was 28.6% at recurrence. Abnormal electroencephalograms were observed in 14 (50%) recurrences. There were 16 (57.1%) recurrences with an increased number of lesions visible on head MRI compared with pre-recurrence levels, while there were 8 (66.7%) recurrences with an increased number of lesions visible on spinal cord MRI compared with pre-recurrence levels. First-line immunotherapy was used at initial disease onset with second-line immunotherapy used only in 1 patient. Second-line immunotherapy was used in 11 recurrences. Conclusion Pediatric GFAP-A tends to recur. The condition at recurrence is milder than at initial disease onset. In most cases, the symptoms seen at recurrence are among those that occurred at initial onset, while new symptoms may occur on recurrence in a small number of patients. In addition to new symptoms and disease worsening during recurrence, abnormal antibody levels, cerebrospinal fluid routine biochemistry test results, electroencephalography results, and radiology findings may also be observed. First-line immunotherapy or long-term combined second-line immunotherapy can be used during recurrence.

Abstract Background Duchenne muscular dystrophy (DMD) is a rare hereditary muscular disease. The role of eosinophils in DMD has not been clarified. This study aims to evaluate the association between peripheral blood eosinophil count and severity and prognosis of DMD. Methods A retrospective cohort study was performed for 145 DMD patients between January 2012 and December 2020. Clinical data of 150 healthy children were collected as a control group. Logistic regression and Cox regression analyses were used to explore the influences of eosinophil count on DMD severity and prognosis. Results Eosinophil count in DMD group was lower than the control group (Z = 2.163, P = 0.031). It was negatively correlated with Vignos scale score, Spearman correlation coefficient was p = 0.245, P = 0.040 (at admission),p = 0.137, P = 0.032 (at follow-up); was a protective factor for high Vignos scale score at admission [odds ratio (OR) = 0.038, 95%CI: 0.002–0.752, P = 0.032] and follow-up (OR = 0.033,95%CI: 0.001–0.121, P = 0.039). The Cox regression analysis indicated that elevated eosinophil count was correlated with better therapeutic efficacy for DMD patients [hazard ratio (HR) = 2.218, 95%CI: 1.154–3.924, P = 0.016]. Conclusion Eosinophil count in peripheral blood was correlated with the severity of DMD. It could indicate the therapeutic efficacy and prognosis of DMD patients to a certain extent. Eosinophils may be a potentially valuable biomarker or therapeutic target for DMD.

OBJECTIVE:To explore the diagnosis, treatment and genetic analysis of an infant with Schaaf-Yang syndrome (SYS).METHODS:An infant suspected for SYS at the Hunan Provincial Children's Hospital on June 10, 2022 was subjected to trio-whole exome sequencing, and Sanger sequencing was used to verify the candidate variant. Structure of the wild-type and mutant proteins was constructed to analyze the potential hazard.RESULTS:The infant was found to harbor a heterozygous frameshifting variant of c.1908delG (p.R637Gfs*65) of the MAGEL2 gene, which was found in neither of his parents. The variant has not been recorded by the public databases, and no relevant literature was retrieved. As the result of the variant, the MAGEL2 protein only retained part of its proline domain, which may lead to destruction and/or down-regulation of its function.CONCLUSION:The c.1908delG (p.R637Gfs*65) variant of the MAGEL2 gene probably underlay the pathogenesis in this child. Combined with his clinical characteristics, the child was diagnosed with SYS. Above finding has also enriched the mutational spectrum of the MAGEL2 gene.

OBJECTIVE:To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM).METHODS:A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients.RESULTS:This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic.CONCLUSION:The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.

Objective Anti-contactin-associated protein 2 (CASPR2)-related autoimmune encephalitis (AE) is more common in adults than in children. Clinical understanding of anti-CASPR2-antibody (Ab)-related AE, diagnosis and treatment standards are lacking in children. Therefore, this retrospective study on clinical symptoms and treatment outcomes in children with anti-CASPR2-Ab-related AE was conducted, to improve the clinical understanding of the disease, its diagnosis and treatment. Methods This study retrospectively assessed children with anti-CASPR2-Ab-related AE from January 1, 2020, to June 30, 2022, in the Department of Neurology at Hunan Children’s Hospital. Data regarding demographics, clinical symptoms, laboratory examinations, electroencephalography (EEG), imaging, and curative were collected. Results Thirteen patients were positive for serum anti-CASPR2-Ab (age at manifestation, 25 months to 13 years old; median, 8.1 years old; male-to-female ratio, 8/5). One patient (P1) had dual Abs, including anti-CASPR2 and anti-N-methyl-D-aspartate receptor Abs; his symptoms were more severe than those of children with anti-CASPR2 Abs alone. The clinical symptoms of the 13 patients with anti-CASPR2 Ab were movement disorders (9/13), consciousness disorders (9/13), abnormal demeanor (8/13), seizures (7/13), language disorders (6/13), fever (6/13), pain (4/13), involuntary exercise (4/13), poor diet (4/13), vomiting (3/13), sleep disorders (3/13), mood disorders (3/13), eczema/itching/redness (2/13), sweating (P8), urinary disorders (P13), and cognitive disorders (P9). No tumors were found in any patient. Additionally, EEG results of six patients were abnormal and imaging findings such as abnormal signals were found in 10 patients. Moreover, all except one patient recovered well after treatment; P1 with overlapping syndrome underwent recovery for more than 2 years. None of the patients who recovered have had a relapse. Discussion and conclusion Anti-CASPR2-Ab-related AE has several clinical manifestations. Anti-CASPR2-Ab levels were higher in male patients than in female patients. Moreover, related tumors are relatively rare. Most patients benefit from immunotherapy and have a lower chance of recurrence in the short term. Furthermore, different from patients who had anti-CASPR2-Ab AE alone, those with overlapping syndrome had a severe and complex condition requiring lengthy treatment and rehabilitation. Additional studies are needed to evaluate the long-term prognosis of these patients.

Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency (ASSD) in Hunan Children′s Hospital were retrospectively analyzed, including data of mass spectra for blood amino acids and acyl carnitine, urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port, the patient was medicated with Glyceryl phenylbutyrate (GPB) and followed up.The patient was a boy aged 7 years and 8 months, who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness, abnormal mental behavior and personality change for 1 week on December 2, 2021.Before GPB treatment, the highest blood ammonia, alanine aminotransferase and aspartate transaminase were 325.2 μmol/L, 465.7 IU/L and 277.3 IU/L, respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42 μmol/L; urine organic acid analysis showed increased urinary orotic acid at 144.2 μmol/L, and increased uracil at 65.1 μmol/L.A pure heterozygous variant of the ASS1 gene (c.1087C>T, p.R363W) was detected.After GPB treatment, the blood ammonia levels were 21.3 μmol/L, 54.6 μmol/L and 62.4 μmol/L on the 41 st, 90 th and 146 th days, respectively.Until July 20, 2022 follow-up visit, the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia, and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.

Objective:To analyze the clinical phenotype and genotype characteristics of children with pyridoxine-dependent epilepsy (PDE) and provide evidence for diagnosis.Methods:Clinical data of 3 children with PDE enrolled in the Department of Neurology of Hunan Children′s Hospital from July 2016 to December 2020 were collected, and whole-exome sequencing (WES) was used for analysis. Pathogenic variants were analyzed and screened using bioinformatics tools combined with clinical phenotype. Sanger sequencing was used to analyze the source of mutations in children′s core family members.Results:Cases 1 (female) and 2 (male) were siblings, both of whom had convulsions within 24 hours after birth. WES results showed that the siblings carried compound heterozygous mutations of c.796C>T (p.R266 *) and c.1553G>C (p.R518T) in the ALDH7A1 gene, coming from the father and mother of the siblings respectively. Both of the mutations have been reported as pathogenic. Case 3, female, developed convulsions at the age of 1. WES results revealed that she carried compound heterozygous mutations of c.1094-109T>A and c.7C>T (p.R3C) in the ALDH7A1 gene, coming from her father and mother respectively. After searching HGMDPro, PubMed, 1000 Genomes, and dbSNP databases, both of the 2 mutations of c.1094-109T>A and c.7C>T (p.R3C) were not reported. The pathogenicity predictions of the 2 mutations were carried out by different biological information analysis software. The results showed that both of the mutations were harmful. All the 3 children had no epileptic seizures after treatment with increased doses of vitamin B6. Conclusions:When infants have unexplained convulsions, especially in the neonatal stage, PDE caused by ALDH7A1 gene mutation should be considered. Pyridoxine precision treatment has a good effect. The 2 de novo mutations of c.1094-109T>A and c.7C>T (p.R3C) enrich the mutation spectrum in the ALDH7A1 gene. WES has the auxiliary significance in the diagnosis of epilepsy.

OBJECTIVE To analyze the clinical phenotype and genetic variants of a child suspected for mitochondrial F-S disease. METHODS A child with mitochondrial F-S disease who visited Department of Neurology, Hunan Provincial children's Hospital on November 5, 2020 was selected as research subject of this study. Clinical data of the child was collected. The child was subjected to whole exome sequencing (WES). Bioinformatics tools were used to analyze the pathogenic variants. Candidate variants were verified by Sanger sequencing of the child and her parents. RESULTS WES revealed that the child has harbored compound heterozygous variants of the FDXR gene, namely c.310C>T (p.R104C) and c.235C>T (p.R79C), which were inherited from her father and mother, respectively. Neither variant has been reported in HGMD, PubMed, 1000 Genomes, and dbSNP databases. Both of the variants have been suggested as deleterious according to the prediction results from different bioinformatics analysis software. CONCLUSION Mitochondrial diseases should be suspected for patients with multiple system involvement. The compound heterozygous variants of the FDXR gene probably underlay the disease in this child. Above finding has enriched the spectrum of FDXR gene mutations underlying mitochondrial F-S disease. WES can facilitate the diagnosis of mitochondrial F-S disease at the molecular level.

ObjectiveThis study aimed to examine the clinical and gene-mutation characteristics of pediatric patients with sodium channel gene mutation-related childhood epilepsy and to provide a basis for precision treatment and genetic counseling.MethodsThe clinical data from 94 patients with sodium channel gene mutation-related childhood epilepsy who were treated at Hunan Children's Hospital from August 2012 to December 2022 were retrospectively evaluated, and the clinical characteristics, gene variants, treatment, and follow-up status were analyzed and summarized.ResultsOur 94 pediatric patients with sodium channel gene variant-related childhood epilepsy comprised 37 girls and 57 boys. The age of disease onset ranged from 1 day to 3 years. We observed seven different sodium channel gene variants, and 55, 14, 9, 6, 6, 2, and 2 patients had SCNlA, SCN2A, SCN8A, SCN9A, SCN1B, SCN11A, and SCN3A variants, respectively. We noted that 52 were reported variants and 42 were novel variants. Among all gene types, SCN1A, SCN2A, and SCN8A variants were associated with an earlier disease onset age. With the exception of the SCN1B, the other six genes were associated with clustering seizures. Except for variants SCN3A and SCN11A, some patients with other variants had status epilepticus (SE). The main diagnosis of children with SCN1A variants was Dravet syndrome (DS) (72.7%), whereas patients with SCN2A and SCN8A variants were mainly diagnosed with various types of epileptic encephalopathy, accounting for 85.7% (12 of 14) and 88.9% (8 of 9) respectively. A total of five cases of sudden unexpected death in epilepsy (SUDEP) occurred in patients with SCN1A, SCN2A, and SCN8A variants. The proportion of benign epilepsy in patients with SCN9A, SCN11A, and SCN1B variants was relatively high, and the epilepsy control rate was higher than the rate of other variant types.ConclusionSodium channel gene variants involve different epileptic syndromes, and the treatment responses also vary. We herein reported 42 novel variants, and we are also the first ever to report two patients with SCN11A variants, thereby increasing the gene spectrum and phenotypic profile of sodium channel dysfunction. We provide a basis for precision treatment and prognostic assessment.

Background:Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a newly defined autoimmune inflammatory demyelinating central nervous system (CNS) disease characterized by antibodies against MOG. Leptomeningeal enhancement (LME) on contrast-enhanced fluid-attenuated inversion recovery (CE-FLAIR) images has been reported in patients with other diseases and interpreted as a biomarker of inflammation. This study retrospectively analyzed the prevalence and distribution of LME on CE-FLAIR images in children with MOG antibody-associated encephalitis (MOG-E). The corresponding magnetic resonance imaging (MRI) features and clinical manifestations are also presented.Methods:The brain MRI images (native and CE-FLAIR) and clinical manifestations of 78 children with MOG-E between January 2018 and December 2021 were analyzed. Secondary analyses evaluated the relationship between LME, clinical manifestations, and other MRI measures.Results:Forty-four children were included, and the median age at the first onset was 70.5 months. The prodromal symptoms were fever, headache, emesis, and blurred vision, which could be progressively accompanied by convulsions, decreased level of consciousness, and dyskinesia. MOG-E showed multiple and asymmetric lesions in the brain by MRI, with varying sizes and blurred edges. These lesions were hyperintense on the T2-weighted and FLAIR images and slightly hypointense or hypointense on the T1-weighted images. The most common sites involved were juxtacortical white matter (81.8%) and cortical gray matter (59.1%). Periventricular/juxtaventricular white matter lesions (18.2%) were relatively rare. On CE-FLAIR images, 24 (54.5%) children showed LME located on the cerebral surface. LME was an early feature of MOG-E (P = 0.002), and cases without LME were more likely to involve the brainstem (P = 0.041).Conclusion:LME on CE-FLAIR images may be a novel early marker among patients with MOG-E. The inclusion of CE-FLAIR images in MRI protocols for children with suspected MOG-E at an early stage may be useful for the diagnosis of this disease.

Abstract Objective To investigate the effect of peripheral blood eosinophil count on the severity and prognosis of Duchenne Muscular Dystrophy（DMD).Method The clinical data of 145 patients with DMD and 150 normal healthy children in the same period were collected retrospectively. The results of the two groups were analysed and compared. Logistic regression and Cox regression analysis were used to explore the influence of eosinophils on DMD. The relationship between eosinophils and the long-term efficacy and prognosis of DMD were followed up.Result Compared with the control group, the eosinophil count of children in DMD group was slightly lower(Z=2.163,p=0.031).Eosino-phil count at visit and follow-up was slightly negatively correlated with muscle strength score to visit and follow-up, and the correlati-on coefficients were as follows: ρ=-0.245，p=0.040，ρ=-0.137，p=0.032.Eosinophils were the protective factor for high muscle strength score of visit,OR=0.007,95%CI(0.001-0.276)，p=0.008,OR=0.038,95%CI(0.002-0.752), p=0.032 after adjusting for age and other factors. Eosinophils were also the protective factor for elevated muscle stre-ngth score at follow-up visit,(OR=0.012,95%CI0.001-0.645,p=0.029), after adjusting for age and other factors (OR=0.033,95%CI0.001-0.121,p=0.039). Univariate analysis found that eosinophils affected the curative effect during follow-up visit, HR=2.739,95%CI(1.294-5.979)p=0.008. Further adjustment for age and other factors multivariate Cox regression analysis found that eosinophils affected the curative effect(HR=1.127,95% CI 1.109-1.246,p=0.020）.Conclusion The eosinophil count in peripheral blood was related to the severity of DMD, and can predict the curative effect and prognosis to a certain extent. Eosinophil count may be a potentially useful predictor.

Objective:To explore the application and effect of teaching and anti-teaching system in clinical skills teaching of the standardized residents training.Methods:Forty pediatric residents of Batch 2018 in Hunan Children's Hospital were randomly divided into the conventional teaching group and the teaching and anti-teaching teaching group, 20 in each group. All of them received the skills training for medical licensing examination. A comparative analysis of the teachers' on-site training time, and the time of mastering individual skill, the skill operation ability, and the comprehensive ability in the two groups was conducted. In addition, teachers and students' satisfaction with teaching and anti-teaching system was investigated by Wenjuanxing, a platform providing questionnaire survey. SPSS 17.0 software was used for t-test and Chi-square test. Results:The teachers' on-site training time [(21.75±3.24) min vs. (48.65±2.91) min] and the residents' time of mastering skills and knowledge [(20.46±3.57) min vs. (30.24±4.73) min] in the teaching and anti-teaching teaching group were shorter than those in the conventional teaching group ( P < 0.05). The scores of clinical skills [(92.96±5.21) points vs. (84.13±3.28) points] and the comprehensive ability [(91.23±5.06) points vs. (85.23±5.72) points] of the residents in the teaching and anti-teaching teaching group were higher than those in the conventional teaching group ( P<0.05). The questionnaire survey showed that the residents had a positive attitude towards the teaching and anti-teaching teaching. They believed that it had the advantage of facilitating full-dimensional viewing of the operation, improving the learning interest, and achieving better learning effect for the residents. Conclusion:The application of teaching and anti-teaching system in the standardized training of residents in children's hospitals can make up for the rare adult clinical operation learning opportunities in children's hospitals, rapidly improve the professional skills of residents, improve the passing rate of medical licensing examination, and help to improve the post competency of residents.

Biallelic NARS2 mutations can cause various neurodegenerative diseases, leading to growth retardation, intractable epilepsy, and hearing loss in early infancy and further progressing to spastic paraplegia, neurodegeneration, and even death. NARS2 mutations are associated with mitochondrial dysfunction and cause combined oxidative phosphorylation deficiency 24 (COXPD24). Relatively few cases have been reported worldwide; therefore, the pathogenesis of COXPD24 is poorly understood. We studied two unrelated patients with COXPD24 with similar phenotypes who presented with intractable refractory epilepsia partialis continua, hearing loss, and growth retardation. One patient died from epilepsy. Three novel NARS2 variants (case 1: c.185T > C and c.251 + 2T > G; case 2: c.185T > C and c.509T > G) were detected with whole-exome sequencing. c.251 + 2T > G is located at the donor splicing site in the non-coding sequence of the gene. The minigene experiment further verified that c.251 + 2T > G caused variable splicing abnormalities and produced truncated proteins. Molecular dynamics studies showed that c.185T > C and c.509T > G reduced the binding free energy of the NARS2 protein dimer. The literature review revealed fewer than 30 NARS2 variants. These findings improved our understanding of the disease phenotype and the variation spectrum and revealed the potential pathogenic mechanism of non-coding sequence mutations in COXPD24.

Abstract Background Nabais Sa‐de Vries syndrome (NSDVS) is a newly identified neurodevelopmental disorder (NDD), characterized by mutations in the SPOP gene, which encodes the speckle‐type BTB/POZ protein. It is divided into two disease subtypes, according to patient facial features, which could be related to altered SPOP protein function. Few studies have documented this syndrome and little is known about its pathophysiology. Herein, we present an unexplained infant case of NDD, possibly the first Asian NSDVS case report. Methods A 7‐month‐old boy presented with an enlarged head circumference, widened eye distance, and a protruding nose. Trio‐whole exome sequencing of the patient's family was performed, and a variant was identified by bioinformatics analysis and further verified by Sanger sequencing. This variant was then identified by molecular dynamics analysis. Finally, a plasmid was constructed in vitro to transfect the human 293 T cells. qPCR and western blotting (WB) experiments were subsequently performed. These analyses verified the variant's transcription and protein expression. Results Trio‐whole exome sequencing was used to identify the SPOP mutation c.67 T > C (p.Cys23Arg). Crystal structure simulations suggest that this single‐residue substitution alters hydrogen bonding with nearby residues. Analysis via qPCR and WB experiments indicated decreased mutant mRNA and protein expression levels. Conclusion Our findings suggest that genetic testing should be performed as soon as possible for children with NDD showing low phenotypic specificity. Prompt testing will provide more accurate diagnoses, which in turn offers evidence to assist in the formulation of rehabilitation training plans, and genetic counseling for patients' families.

Background:The incidence and prevalence of autoimmune encephalitis (AE) is gradually increasing in pediatric patients (between the ages of 3 months and 16 years). The aim of this retrospective observational study was to investigate the clinical characteristics and short-term prognosis of children with antibody-mediated AE at Hunan Children's Hospital.Methods:Antibody analysis of blood and/or cerebrospinal fluid was performed in suspected AE patients admitted to the Department of Neurology, Hunan Children's Hospital from June 2014 to June 2021. Ultimately, 103 patients were diagnosed with antibody-mediated AE and were enrolled in this study. Clinical data and corresponding demographic, clinical characteristics, laboratory and imaging data, treatment, and prognosis data were collected and analyzed.Results:In our study, 103 AE patients with antibody-positive were identified. The main subtype of AE in our cohort was anti-NMDAR encephalitis. Few patients have anti-CASPR2 encephalitis, anti-GABABR encephalitis, or anti-LGI1 encephalitis. In our AE patients, the most common clinical manifestations were behavioral symptoms, seizures, and involuntary movements, with seizures being the most common initial symptom. All patients underwent brain magnetic resonance imaging (MRI) and electroencephalography (EEG). Forty-five (43.7%) patients had abnormal MRI findings. And 96 (93.2%) patients had abnormal EEG results. All 103 patients were given first-line immunotherapy, 21 of which were also treated with the combination of the second-line immunotherapy. All surviving patients were followed up for at least 6 months. Seventy-seven patients recovered completely, 23 had sequelae of different degrees, and 3 died. Eight patients had one or more relapses during the follow-up period.Conclusions:AE is a treatable disease that can occur in children of all ages. The mortality rate is low, as most patients have a good response to immune therapy. Compared with the older children, infants and young children (≤ 3 years old) with anti-NMDAR encephalitis have a higher incidence of fever and status epilepticus, more severe condition, higher PICU admission rate and worse prognosis. AE patients with high maximum mRS scores and PICU admissions may require second-line immunotherapy.

目的 总结KCNT1基因变异相关婴儿癫痫伴游走性局灶性发作(EIMFS)的临床特点.方法 回顾性分析2018年8月至2020年5月就诊于湖南省儿童医院神经内科的KCNT1基因变异相关的EIMFS患儿,对其临床表现、头颅影像学、脑电图特点、治疗及随访情况进行分析总结.结果 共4例患儿,均携带不同的KC-NT1基因杂合突变,其中1例为遗传性变异,3例为新生变异.4例患儿起病年龄2～110 d,发作类型均为频繁的多种类型的游走性局灶性发作,其中1例病程中有癫痫持续状态,1例患儿病程中出现痉挛发作.4例患儿均应用多种抗癫痫药物,1例暂时有效,1例癫痫发作部分控制,2例发作未控制.2例患儿应用生酮饮食治疗,无明显疗效,1例患儿应用奎尼丁治疗,无明显疗效且出现QT间期延长.4例患儿均有明显运动智力发育落后.结论 KCNT1基因变异EIMFS起病年龄早,多在新生儿期及婴儿期早期,主要发作类型为游走性的局灶性发作,发作频繁,均伴随运动、智力发育落后,对抗癫痫药治疗反应差,奎尼丁及生酮饮食疗效尚需大样本的治疗研究进一步明确.

Objective:To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children.Methods:Children hospitalized in the Department of Neurology, Hunan Children's Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed.Results:A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff's brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman's rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions.Conclusions:The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.

目的 探索重大突发传染性公共卫生事件下住院医师规范化培训基地的有效管理措施.方法 2020年疫情防控期间对我院儿科专业基地的99名住院医师,通过教学工作安排调整、开展互联网知识培训、日报告健康情况、返岗前摸底排查、调整排班、心理援助、关心慰问等一系列措施保障培训任务和医院工作有序开展,使用问卷星软件调查住院医师知识掌握情况、近期满意度及健康情况.结果 99名住院医师除3名有疫源地区人员接触史需居家隔离14 d外,其余96名住院医师及时返岗,住院医师均未发生感染.99名住院医师均参加重大突发传染性公共卫生事件防控知识及法律法规考试,99名住院医师全部通过考试,其中94名优秀,优秀率为94.95％.在职业荣誉认同感方面,39名强烈认同,58名基本认同,2名不确定.在值班合理性认同度方面,41名认为非常合理,58名认为基本合理,无人认为不合理.在整体满意度方面,42名为基本满意,57名为非常满意,无不满意者.无住院医师发生疫情感染.结论 以住院医师为中心的多维度管理措施有助于缓解其焦虑情绪,增强职业认同感,避免疫情人际传播,提升满意度,达到防控与住院医师规范化培训的有关要求.