[Clinical and prognostic analysis of opsoclonus-myoclonus-ataxia syndrome in children].

Objective: To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Methods: A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children's Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results: There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ²=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ²=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence (OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis (OR=11.64 (1.27-106.72), P=0.030). Conclusions: OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

[Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) ß-thalassemia mutation with α-thalassemia and review of the literature].

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) ß-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and ß-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (ß-88 C>G/ßN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

[Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma].

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION: MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

[Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children].

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.

[Clinical characteristics and gene analysis of SYNGAP1-related epilepsy in children].

Objective: To summarize the clinical characteristics of SYNGAP1-related epilepsy in children. Methods: Data of 13 patients with SYNGAP1 gene variants diagnosed with epilepsy at Department of Neurology, Beijing Children's Hospital were collected retrospectively from March 2017 to October 2020 and the patients were followed up. The clinical features, electroencephalogram(EEG), brain imaging, gene results and treatment were summarized. Results: Twelve patients were followed up successfully among the 13 patients with SYNGAP1 variants. The last follow-up age was 5 years and 7 months (3 years and 1 month to 9 years).The onset age of seizures was 2 years (4 months to 3 years). Seizure types included eyelid myoclonia with or without absence (9 cases), myoclonic seizure (5 cases), atypical absence (4 cases), suspicious atonic seizures(4 cases),unclassified fall attack (6 cases), and the frequency of seizures varied from several times to more than 100 times per day. Four cases had the mimic phenotype of myoclonic astatic epilepsy. The seizures of 10 cases could be triggered by eating (5 cases), emotion (5 cases), fever (3 cases), voice (2 cases), fatigue (2 cases), etc. Electroencephalography (10 cases) showed interictal generalized or focal epileptiform discharges (9 cases), and atypical aphasia (4 cases), myoclonic seizure (2 cases) and eyelid myoclonic seizure (1 case) were monitored. Of the 12 cases, 9 were added with valproate, all of which were effective (the frequency of seizures reduced>50%). Five cases received combined levetiracetam, in 3 the treatments were effective. To last follow-up, 3 cases were seizure free from 6 months to 1 year and 1 month, but the remaining 7 cases still had seizures, one or several times per day. All 13 cases had developmental retardation (speech ability impaired mostly), 2 cases were severe, 10 cases were moderate, 1 case was mild. The SYNGAP1 gene variants of 13 patients were all de novo, including 12 variants. Among them, 4 were frameshift variants, 4 were nonsense variants, 2 were missense variants and 2 were splice site variants. Conclusions: Patients with SYNGAP1-related epilepsy have an early onset age and many seizure types. The main seizure type is eyelid myoclonia with or without absence, and other seizure types include myoclonic seizure, atypical absence, unclassified fall attack, etc. Valproate is effective in most patients, but seizures in some patients might be intractable. Most patients have developmental delay (mainly moderate and severe), speech ability impaired mostly.

[Clinical and imaging features of Chlamydia psittaci pneumonia: an analysis of 48 cases in China].

Objective: To explore the clinical characteristics, imaging findings, laboratory tests and treatment strategies for Chlamydia psittaci pneumonia. Methods: From January 1, 2019 to January 20, 2021, 48 cases of Psittacosis from 11 hospitals in China were diagnosed via metagenomic next-generation sequencing(mNGS). The data of all patients on occupational history, clinical manifestations, laboratory tests, chest computed tomography(CT)findings, treatment outcomes and prognosis were retrospectively analyzed. Results: Among the 48 patients, there were 29 males and 19 females, with a mean age of (57.1±10.3) years. Thirty patients had a confirmed history of exposure to poultry. The onset to admission interval was (6.5±3.2) days, and hospital stay was (12.4±4.8) days. Clinical manifestations included fever (100%, 48/48), relative bradycardia (71%, 34/48), cough (54.2%, 26/48), sputum (27.1%, 13/48), fatigue (16.7%, 8/48), headache and delirium (20.8%, 9/48), and gastrointestinal symptoms (16.7%, 8/48). Laboratory data showed that white blood cells were (8.0±3.8)×109/L, and the proportion of neutrophils increased in 44 patients. The level of C-reactive protein was (155.3±74.1)mg/L, and that of procalcitonin (PCT)in 59.5% of patients was more than 0.5 µg/L. Percentages of patients with increased lactate dehydrogenase and creatine kinase were 82.9% and 45.2%, respectively. Chest CT scans showed unilateral lung involvement in 34 cases(70.8%) and single lobe involvement in 27 cases(56.3%).The most common imaging change was consolidation, with 38 cases (79.2%) showing lobar consolidation. In terms of treatment, 25 patients were treated with fluoroquinolones alone, 6 patients with doxycycline alone, and 13 patients with combined treatment. The combined-treatment group and the doxycycline alone group were similar in the course of defervescence. The combined treatment group and the doxycycline alone group were both superior to the fluoroquinolones alone group. However, 11 patients were admitted to ICU, all of them received artificial ventilation, and 5 cases developed shock, and one died. Conclusions: Chlamydia psittaci pneumonia is an animal-derived infectious disease with unique features in clinical symptoms, laboratory tests and chest imaging. Appropriate treatment is able to significantly shorten the course of disease and improve the prognosis.

[Bilateral papillary renal cell carcinoma following kidney transplantation: A case report].

With the continuous development of kidney transplantation technique, the survival time after kidney transplantation is gradually prolonged. Thus, the malignant tumor has been the important influencing factor on the long-term survival for kidney transplantation patients. Renal cell carcinoma is a relatively common tumor after kidney transplantation. Besides, clear cell renal cell carcinoma and papillary renal cell carcinoma are the relatively common pathological types for renal cell carcinoma following kidney transplantation. However, bilateral renal cell carcinoma following kidney transplantation is comparatively rare. In this article, we presented a case of bilateral papillary renal cell carcinoma, which occurred after kidney transplantation. And the diagnosis and treatment were introduced in detail. The patient was 37 years old, and he underwent kidney transplantation 13 years ago in our hospital, because of kidney failure. After kidney transplantation, he had regular medical check-up every year. In this year, his urological ultrasound results indicated bilateral renal tumors. And then, he received abdominal and pelvic computed tomography, and the result also showed bilateral renal tumors, which were likely to be malignant tumors. After adequate consultation, the patient chose surgical treatment. The patient received long-term immunosuppressive therapy, because of kidney transplantation. Considering this, the surgeon decided to choose a staging surgical treatment, in order to reduce the bad influence of one-stage surgery. Then, the patient first underwent retroperitoneal laparoscopic radical nephrectomy for right renal tumor in our hospital, and he had no complications after operation. The pathological results showed papillary renal cell carcinoma. He was discharged successfully. He underwent retroperitoneal laparoscopic radical nephrectomy for left renal tumor in our hospital one month later, and he had no complications after operation. The pathological results also showed papillary renal cell carcinoma. He was discharged successfully two days after surgery. In the 3-month follow-up, the patient was recovering well. To sum up, the incidence of bilateral renal cell carcinoma following kidney transplantation is relatively rare, and bilateral radical nephrectomy is effective and safe treatment. Above all, it is the patient's condition that determines the choice of staging surgery or simultaneous surgery.

[The etiology of 340 infants with early-onset epilepsy].

Objective: To investigate the etiology of epilepsy onset before 6 months old and improve clinical understanding. Methods: The medical history, electroencephalogram, brain imaging, genetic examination and other clinical data of 340 patients who were diagnosed with epilepsy with onset under 6 months of age and were hospitalized in the Department of Neurology, Beijing Children's Hospital, Capital Medical University between January 2017 and December 2018 were retrospectively analyzed. Rank sum test was used to compare the ages of onset of different etiologic groups. Results: Of the 340 patients, 196 were males and 144 were females. The age of onset was 90.5 (48.0, 135.5) days. In the 250 (73.5%) underwent genetic test, 103 (41.2%) had pathogenic or likely pathogenic variants, involving 43 single gene variants and 2 chromosomal abnormalities. Seventy-nine patients (23.2%) had genetic etiology, 66 (19.4%) had structural etiology, 19 (5.6%) had metabolic etiology, 13 (3.8%) had multiple etiologies, and 163 (47.9%) had unknown etiology. In the 79 cases with genetic etiology, 30 single gene variants were detected, including 19 cases of PRRT2, 10 cases of KCNQ2, 7 cases of SCN1A, 6 cases of SCN2A, 6 cases of STXBP1, 5 cases of CDKL5, 2 cases of ARX, and 1 case of each of 23 gene variants. Two cases had chromosomal abnormalities which were 21-trisomy and 16p11.2 microdeletion syndrome respectively. Among the 66 cases with structural etiologies, 37 cases had acquired factors such as perinatal brain injury, 28 cases had congenital factors such as cortical malformation and 1 case was perinatal brain injury combined megalencephaly. The onset age of genetic etiology was 95 (26, 128) days, that of structural etiology was 90 (58, 30) days, and that of metabolic etiology was 57 (30, 90) days. The onset age of metabolic etiology was earlier than that of structural etiology (U=436.500, P=0.044). Conclusions: Genetic etiology is the most common defined etiology of infants with early-onset epilepsy aged 0-6 months, and there are certain differences in the age of onset between different etiologies. Proper application of genetic test is helpful to identify the etiology and guide treatment.

[Molybdenum cofactor deficiency type B manifested as Leigh-like syndrome: a case report and literature review].

Objective: To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome. Methods: The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children's Hospital and Hebei Children's Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms "MOCS2" "molybdenum cofactor deficiency" "Leigh-like syndrome,MOCS2" "molybdenum cofactor deficiency, Leigh-like syndrome". The phenotypes and genotypes of MoCD-B were summarized. Results: A 7 months and 14 days old boy with the chief complaint of "cough for 6 days, abnormal posture for 4 days and fever for 2 days" was admitted to Hebei Children' Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support. Conclusions: Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis.

[Analysis of self-control trial results of narrow band imaging and white light in transurethral resection of bladder tumor].

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION: TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.

[Clinical and genetic analysis of childhood-onset myoclonus dystonia syndrome caused by SGCE variants].

Objective: To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. Methods: The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children's Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively. Results: Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively. Conclusions: SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.

[Clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation].

Objective: To summarize the clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation. Methods: The clinical data, gene variation and treatment outcome of 12 children with focal epilepsy caused by GATOR1 complex gene variation admitted to Beijing Children's Hospital Affiliated to Capital Medical University from June 2016 to October 2018 were retrospectively analyzed. Results: There were 7 males and 5 females in 12 cases. The epilepsy onset age was 5.5 (3.0, 12.0) months, and from 11 days to 16 months of age. The epileptic seizure types were all focal motor seizures, and one case combined with epileptic spasms. The frequency of seizures in all patients was more than one time per day. Seven cases had frontal lobe epilepsy and two cases had lateral temporal lobe epilepsy. One case had a family history of febrile seizures and two had a family history of suspicious epilepsy. Epileptic form discharges were observed in 9 patients during the interictal phase by electroencephalograms (EEG), and all of them were focal discharges. Eight cases had clinical seizures detected by EEG, in 4 of whom the seizures were originated in frontal region. There were no abnormalities in brain magnetic resonance imaging in 11 cases whereas 1 case had malformation of cortical development of left frontal lobe. Eight patients had DEPDC5 gene variation, one had NPRL2 gene variation, three had NPRL3 gene variation. One case had de novo variation and the other 11 had hereditary variation. There were 11 types of gene variation, including 5 nonsense variations, 3 missense variations, 2 frame shift variations and 1 in frame deletion variation. There was no clear relationship between the clinical phenotype and the genotype. During the follow-up period from 6 months to 2 years and 6 months, 6 cases had seizure control, 3 of them were controlled by oxcarbazepine. The other 6 cases had drug-refractory epilepsy, 2 of them failed with vagus nerve stimulation and ketogenic dietary therapy as well, meanwhile combined with mental retardation. Conclusions: GATOR1 complex gene variation can lead to genetic focal epilepsy, which usually has early onset with frequent seizures. Most of the patients have focal epileptic form discharges on EEG, and there is usually no structural lesion in brain imaging. Most of the patients have hereditary loss-of-function variations. Approximately half of cases are drug-resistant epilepsy.

[Clinical features of 19 children with Bickerstaff brainstem encephalitis].

Objective: To summarize the clinical features of Bickerstaff brainstem encephalitis (BBE) in children. Methods: In this retrospective study, data of 19 patients with BBE (11 males and 8 females) were collected from Department of Neurology, Beijing Children's Hospital from October 2015 to January 2018. The clinical features, treatment and prognosis were analyzed. Results: The onset age of BBE ranged from 1 year and 8 months to 12 years and 11 months. There were 18 cases with preceding infection. The most common infection was upper respiratory tract infection (9 cases), followed by simple fever (5 cases). The most common initial neurological symptoms were lethargy or disturbance of consciousness (8 cases), followed by limb weakness (5 cases). There were 6 cases of simple BBE and 13 cases of BBE overlapping Guillain-Barré syndrome (GBS). Besides the characteristic triad of altered mental status, ataxia, and ophthalmoplegia, there were other symptoms including convulsion (5 cases), diplopia (3 cases), nystagmus (7 cases), facial muscular weakness (7 cases),bulbar palsy (13 cases) and autonomic nerve symptoms (9 cases). Hypo or areflexia was seen in 16 cases. Positive Babinski's signs were seen in 8 cases. Hyponatremia was present in 10 cases in whom 4 showed severe hyponatremia. Albumin-cytological dissociation of cerebrospinal fluid was seen in 10 cases. The autoimmune antibodies were examined in all 19 patients. Anti-ganglioside antibodies including anti-GM1 IgG antibody was positive in 2 patients and one of whom was also found with positive anti-GD1b IgG antibody. Anti-GQ1b IgG antibody was present in 2 patients. Electromyography was performed in 14 cases and 8 cases, who were all BBE overlapping GBS, showed neurological damage. A total of 16 cases were monitored by video electroencephalography and 8 cases showed slow waves of background. In addition to, interictal focal discharge was detected in 2 cases. T2 fluid-attenuated inversion recovery (FLAIR) sequence abnormal signals were detected in 3 of 18 cases performed brain magnetic resonance imaging (MRI), and lesions involved with brainstem, basal ganglia, thalamus, cerebellum, corpus callosum and cerebral cortex. Lesions involved cervical and thoracic spinal cord were found in 1 out of 11 cases for whom spinal cord MRI was performed. All of the 4 cases who underwent enhanced MRI of spinal had partial nerve roots enhancement. All of the 19 patients received 1 to 2 courses of intravenous immunoglobulin therapy, and 2 cases also received plasma exchange. Fifteen cases received steroid therapy. The following-up period ranged from 3 months to 2.5 years. Two cases were lost to follow-up. Twelve cases achieved a full recovery within 3 months. Three cases recovered within 6 months. One case still had slight limb weakness and ataxia after 1 year and 8 months of follow-up, and another case had left autonomic nerve symptoms in the follow-up of 2 years and 3 months. Both of them were BBE overlapping GBS. Conclusions: Children's BBE is similar to that in adults, and is frequently found overlapped with GBS. Furthermore, it is sometimes accompanied by central nervous system demyelination disease. The antiganglioside antibodies are not often detectable. Immunoglobulin therapy could usually achieve good response. The prognosis of simple BBE is good in most situations. For BBE overlapping GBS, the more severe the limb weakness during the peak of disease is, the slower the recovery would be.

[Feasibility study of blood oxygen level-dependent magnetic resonance imaging in evaluating the response of metastatic lymph nodes of rabbit VX2 tumor to radiotherapy].

Objective: To investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (MRI) in evaluating the response of metastatic lymph nodes of rabbit VX2 tumor to radiotherapy. Methods: Twenty-eight healthy New Zealand white rabbits which were provided by the Laboratory Animal Center of Soochow University, male or female, 2 to 3 months, weighing 2 to 3 kg, were used to establish the animal model of VX2 tumor popliteal fossa metastatic lymph node, and then were divided into either the radiotherapy group (n=16) or the control group (n=12). The radiotherapy group received a 20 Gy radiotherapy per rabbit, the control group received sham radiotherapy. All rabbits underwent MRI scan on four time points, including before (0 day), 3rd, 7th and 14th days after radiotherapy. The two parameters of size and R(2*) value (s(-1)) of lymph node were measured. At each time point,two rabbits in each group were sacrificed randomly to resect lymph nodes for pathological examination, and two parameters of microvessel density (MVD, strip/HP) and apoptosis index (AI, %) were analyzed. The parameters among the four time points in each group or between the two groups were compared. The correlation of lymph node size and R(2*) value with MVD or AI was analyzed, respectively. Results: A significant size difference was neither between the two groups or among the each time points in each group (P>0.05). The R(2*) of lymph node in the radiotherapy group was (29.6±1.7),(36.8±2.6),(44.8±5.8) and (57.7±6.2) s(-1) at the time points of 0, 3, 7 and 14 days, respectively, showing a gradual increase trend; MVD was (52.3±2.5),(41.0±3.6),(34.0±3.6) and (22.7±2.5) strip/HP respectively, showing a decreasing trend; AI was 12.8%±0.5%,14.9%±0.6%,20.6%±0.5% and 27.5%±0.7% respectively, showing a gradual increase trend (all P<0.05). In the control group, both R(2*) value and AI among the four time points did not change statistically (all P>0.05), but MVD showed a gradual increase trend,(50.0±3.0),(53.0±1.7),(60.3±2.5) and (70.0±2.0) strip/HP, respectively, P<0.05. There were significant differences in R(2*) and MVD at 3, 7 and 14 days, in AI at 7 and 14 days between the two groups (all P<0.05). There was a linear correlation of R(2*) value, but not of size, with MVD and AI (r=-0.87 and 0.94, respectively). Conclusion: Blood oxygen level-dependent MRI can indirectly reflect the hypoxic status of metastatic lymph nodes after radiotherapy, and has potential value in evaluating the response of metastatic lymph nodes to radiotherapy.

[Single-center study of laparoscopic radical nephrectomy with Mayo 0-2 level inferior vena cava thrombectomy].

OBJECTIVE: To investigate the safety and feasibility of laparoscopic treatment for renal carcinoma with Mayo 0-2 level venous thrombosis. METHODS: From January 2015 to February 2018, 58 renal carcinoma cases with venous thrombus underwent laparoscopic radical nephrectomy with inferior vena cava thrombectomy in Department of Urology, Peking University Third Hospital, of which, 51 cases were male, and 7 female, aged 29-82 years. According to the Mayo grade classification, 20 cases were level 0, 20 cases were level 1, and 18 cases were level 2, with left side being 22 cases, and right side 36 cases. The patients except for those complicated with hemorrhagic diseases, cardiac and pulmonary insufficiency, or those who could not tolerate anesthesia and surgical contraindications, underwent the operation after comprehensive examinations. RESULTS: The 58 cases of renal tumor with venous tumor emboli were successfully completed with the surgeries, including 50 cases of totally laparoscopic surgery, 8 cases of laparoscopy surgery from convert to open (among the patients who were converted to open surgery, 7 were complicated with grade 2 tumor thrombus and 1 with grade 1 tumor thrombus). The main reasons for converting to open surgery were huge tumors (the largest of which was about 16 cm in diameter), severe adhesion and difficulty of separation. For different patients, different surgical methods and procedures were adopted according to the tumor direction and the different grade of tumor thrombus. Radical nephrectomy combined with vena cava tumor thrombus removal was performed in 55 cases and segmental resection of vena cava in 3 cases. The operation time was 132-557 min, and blood loss was 20-3 000 mL. Post-operative pathological types: 51 cases were clear cell carcinoma, 5 cases were type 2 of papillary carcinoma, 1 case was squamous cell carcinoma, and 1 case was chromophobe cell tumor. In the study, 47 cases were followed up for 1-36 months, and 4 cases died (the survival time was 5-15 months, with an average of 10.2 months). CONCLUSION: Laparoscopic radical nephrectomy with inferior vena cava thrombectomy is a reasonable choice for renal tumor with Mayo 0-2 level venous thrombosis. For different tumor directions and different grades of tumor thrombus, an appropriate operation plan can give the maxim benefit to the patients with skillful surgeons.

[Clinical phenotypes of TBC1D24 gene related epilepsy].

Objective: To summarize the clinical features of TBC1D24 gene mutations associated with epilepsy. Methods: All the patients with TBC1D24 gene compound heterozygous mutations were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2015 to July 2017, and the features of clinical manifestations, electroencephalogram, and neuroimaging were analyzed. Results: Eighteen cases with TBC1D24 gene compound heterozygous mutations were included. The age of seizure onset was 1 day to 8 months, and the median age was 90 days. Seizure types included generalized tonic-clonic seizures (GTCS) in 3 cases, focal seizures in 18 cases, myoclonus in 18 cases, and 17 cases had focal myoclonus and myoclonus status. The focal myoclonus involving one or multiple muscle groups, sometimes migrating and alternating, lasting up to minutes to several days, and could be terminated by sleep or sedation drugs. In 11 cases, myoclonus was exacerbated by fever or infections, and 2 cases developed into myoclonic status during infection, in a severe case with the loss of consciousness. The magnetic resonance imaging (MRI) of seven patients was abnormal, including cerebral atrophy or cerebellar atrophy with abnormal signals. Segment myoclonus was captured in 10 patients, but without correlated epileptiform discharges. There were ten cases had varying degrees of developmental delay, 7 were normal, and one patient died of status epilepticus at the age of 4 months. Three cases had hearing disorders. In the 18 patients, the clinical phenotype of 4 cases consisted of epilepsy of infancy with migrating focal seizures, 2 with progressive myoclonus epilepsies, 1 with Dravet syndrome, 1 with DOORS syndrome, and 3 with unclassified epileptic encephalopathy. Conclusions: The clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated by sleep or sedation drugs. Mental retardation involved or not, neuroimaging could present with cerebral atrophy or cerebellar atrophy with abnormal signals.

[The effect of ambient PM(10) on sperm quality in Wuhan].

Objective: To investigate the effect of exposure to particulate matter ≤10 µm in aerodynamic diameter (PM(10)) on sperm quality in different stages of sperm development. Methods: This cross-sectional study included 1 827 patients attending the reproductive medicine center in Renmin Hospital of Wuhan University during April 2013 to January 2015. Air pollution data from January 2013 to January 2015 was obtained from the database of Wuhan Municipal Environmental Protection Bureau. The generalized linear model was employed to assess the association between each exposure variables and sperm parameters for several exposure windows (0-9, 10-14, 15-69, 70-90, 0-90 days before sampling) . Results: The average levels of PM(10) was (116.2±71.6) µg/m(3) during the research period. Sperm volume was (75.4±49.1) ×10(6)/ml in sample population, (29.4±16.2) % in progressive motility and (51.8±21.6) % in total motility. Exposure to PM(10) was inversely associated with sperm concentration (ß:-0.319; 95%CI:-0.529,-0.046) during 70-90 lag days. PM(10) exposure during the 0-90 lag days was significantly associated with progressive motility (ß:-0.312; 95%CI:-0.527,-0.097) and total motility (ß:-0.347; 95%CI:-0.636,-0.059) after adjusted for age, education level, BMI, smoking, abstinence time, temperature, humidity and season. Conclusion: Exposure to PM(10) was associated with statistically significant decrements in sperm concentration and motility, and the adverse impact on sperm concentration was significantly in early phases of spermatogenesis.