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1.
Artigo em Inglês | MEDLINE | ID: mdl-32145913

RESUMO

The blood-spinal cord barrier (BSCB) is an effective, tightly-connected tissue that reduces secondary spinal cord injury (SCI) by decreasing blood cell infiltration, inflammation, and neuronal cell death during primary SCI. However, the methods and molecular mechanisms of BSCB openness remain elusive. In the present study, we found that microRNA429 (miR-429) plays a vital role in the opening of the blood-spinal cord. Inhibiting the expression of miR-429 (antagomiR-429) resulted in increased expression levels of the tight junction (TJ) proteins, ZO-1, occludin, and claudin-5, in the BSCB and reduced BSCB permeability. Moreover, overexpression of miR-429 (agomiR-429) had the opposite effect. Krüppel-like factor 6 (KLF6) is a transcription factor of the zinc-finger family. Using RT-qPCR and western blotting, we found that miR-429 can negatively regulate the expression of the KLF6. Co-transfection of KLF6 and miR-429 demonstrated that miR-429 negatively regulates KLF6 to mediate TJ protein expression and BSCB permeability. Based on these results, we suggest that KLF6 may be a downstream target of miR-429, mediating TJ protein expression to regulate the BSCB.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32170045

RESUMO

OBJECTIVE: To investigate whether the use of mycophenolate mofetil (MMF) could reduce the relapse risk in patients with myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorders (MOGADs). METHODS: This prospective observational cohort study included patients with MOGAD at Peking Union Medical College Hospital between January 1, 2017, and April 30, 2019. The patients were divided into 2 groups: those with (MMF+) or without (MMF-) MMF therapy. The primary outcome was relapse at follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) for relapse. RESULTS: Seventy-nine patients were included in our MOG cohort. Fifty (63.3%) were adults at index date, and 47 (59.5%) were women. Fifty-four (68.4%) were in the MMF+ group, and 25 (31.6%) were in the MMF- group. Clinical and demographic factors, MOG-IgG titer, and follow-up time (median, 472.5 days for MMF+, 261.0 days for MMF-) were comparable between the groups. Relapse rates were 7.4% (4/54) in the MMF+ group and 44.0% (11/25) in the MMF- group. Of all potential confounders, only the use of MMF was associated with reduced risk of relapse. The HR for relapse among patients in the MMF+ group was 0.14 (95% CI, 0.05-0.45) and was 0.08 (95% CI, 0.02-0.28) in a model adjusted for age, sex, disease course, and MOG-IgG titer. MMF therapy also remained associated with a reduced relapse risk in sensitivity analyses. Only one patient (1.9%) discontinued MMF therapy because of adverse effect. CONCLUSIONS: These findings provide a clinical evidence that MMF immunosuppression therapy may prevent relapse in patients with MOGAD. CLASSIFICATION OF EVIDENCE: This study provides class IV evidence that for patients with MOGAD, MMF reduces relapse risk.

4.
Front Genet ; 10: 370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105743

RESUMO

Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.

5.
Front Pharmacol ; 10: 259, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30914958

RESUMO

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders caused by genetic defects in neuromuscular junctions. Mutations in CHAT, encoding choline acetyltransferase, cause congenital myasthenic syndrome with episodic apnea (CMS-EA), a rare autosomal recessive disease characterized by respiratory insufficiency with cyanosis and apnea after infections, fever, vomiting, or excitement. To date, no studies have reported deletions comprised of multiple exons. Here, using next generation sequencing, we identified compound heterozygous mutations, namely a large maternally inherited deletion, including exons 4, 5, and 6, and a paternally inherited missense variant (c.914T>C [p.Ile305Thr]) in CHAT in a Chinese patient with a severe phenotype of CMS-EA. Furthermore, the large deletion was also validated by real-time fluorescence quantitative polymerase chain reaction. The patient was a 10-month-old boy, who presented with a weak cry and feeding difficulties soon after birth, ptosis at 4 months old, episodic apnea after fever at 9 months old, and respiratory insufficiency with cyanosis and apnea that required intubation after a respiratory tract infection at 10 months old. Unfortunately, he died in the Pediatric Intensive Care Unit soon after hospitalization. The patient's elder sister had similar clinical manifestations, and she died prior to the age of 2 months old without a diagnosis. Genotype-phenotype correlation analysis revealed that loss-of-function mutations in exons 4-6 of CHAT might cause more severe CMS-EA. To our knowledge, this is the first study to show compound heterozygous CHAT mutations consisting of a large deletion and missense mutation in a patient with CMS-EA.

6.
Neurol Sci ; 40(3): 523-528, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30564963

RESUMO

OBJECTIVE: This study aims to describe the associations between genetic polymorphisms and therapeutic effect of valproic acid (VPA) in children with focal seizures. METHODS: Eighty-nine children with focal seizures on VPA therapy were enrolled. Patients' basic information, dosage regimens, and plasma concentrations were recorded. A 1-year follow-up was performed to evaluate the treatment response. Sixty-six single nucleotide polymorphisms involved in the metabolism, transport, and target receptor of VPA were identified, and their associations with VPA response were analyzed using logistic regression adjusted by various influence factors. Selected polymorphisms involved in the metabolism, transport, and target receptor of VPA were not associated with treatment effect in children with focal seizures. RESULTS: Three variants, rs9313892 (GABRA6, G > A, OR = 2.73, 95% CI 1.00 to 7.48, P = 0.051), rs4921195 (GABRA6, T > C, OR = 2.71, 95% CI 0.99 to 7.42, P = 0.053), and rs424740 (GABRG2, A > T, OR = 0.39, 95% CI 0.15 to 1.01, P = 0.053) had the potential to be associated with the VPA response. CONCLUSION: Selected genetic polymorphisms were not significantly associated with VPA response in children with focal seizures. However, three GABR variants showed potential to be associated with the response to VPA. Further and larger studies are warranted to confirm the results.


Assuntos
Anticonvulsivantes/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Receptores de GABA-A/genética , Convulsões/tratamento farmacológico , Convulsões/genética , Ácido Valproico/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Modelos Logísticos , Masculino
8.
Sci Rep ; 7(1): 13686, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29057985

RESUMO

There are two genetics complementary groups Cockayne syndrome type A and B (CS-A and CS-B OMIM 216400, 133540), which is a rare autosomal recessive segmental progeroid syndrome. Homozygous or compound heterozygous mutations in the excision repair cross-complementation group 8 gene (ERCC8) result in CS-A, and mutations in ERCC6 result in CS-B. Homozygous ERCC6/ERCC8 mutations also result in UV-sensitive syndrome. In this study, twenty-one Han Chinese patients with CS were investigated to identify mutations in ERCC8/ERCC6, of which thirteen cases with CS-A were identified with the mutations of ERCC8. There are five types mutations of ERCC8 in our study, such as exon 4 rearrangement, c.394_398delTTACA, c.299insA, c.843 + 2 T > C, and c.2 T > A. An estimated frequency of exon 4 rearrangement accounts for 69.23% and c.394_398delTTACA accounts for 11.53% in our cohort. Haplotype analysis revealed that the exon 4 rearrangement and c.394_398delTTACA mutations originated from a common founder in the Chinese population respectively. With the identification of three novel ERCC8 mutations, this study expanded the molecular spectrum of known ERCC8 defects, and furthermore, suggests that the exon 4 rearrangement and c.394_398delTTACA mutations may be a common underlying cause of CS-A in the Chinese population, which is different from that in other populations.


Assuntos
Síndrome de Cockayne/genética , Enzimas Reparadoras do DNA/genética , Mutação , Fatores de Transcrição/genética , Adolescente , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , China , Síndrome de Cockayne/metabolismo , Estudos de Coortes , Enzimas Reparadoras do DNA/metabolismo , Feminino , Haplótipos , Humanos , Masculino , Fenótipo , Fatores de Transcrição/metabolismo
9.
Brain Dev ; 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28552323

RESUMO

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

10.
Childs Nerv Syst ; 33(2): 297-305, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27957632

RESUMO

OBJECTIVE: Patients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism. METHOD: This study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children. RESULT: A total of 42 patients were included and assigned into AED and non-AED treatment groups in a 1:2 matched case-control study. Results show that the seizure outcome after 1 year of AED treatment is not significantly different from that of the control. In the subgroup analysis of patients with subcortical calcifications, the seizure outcome is still not significantly different from that of the control. CONCLUSION: Thus, AED treatment cannot improve the seizure outcomes in children with parathyroid disorder, even in such cases as suspected structural seizure caused by subcortical calcifications. Clinicians must take adequate considerations on the use of AEDs in these patients. Epileptic seizures, as the first symptom of hypoparathyroidism in children, do not require epilepsy drugs.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/etiologia , Hipoparatireoidismo/complicações , Adolescente , Cálcio/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Tomógrafos Computadorizados
11.
Technol Health Care ; 24 Suppl 2: S707-15, 2016 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-27177101

RESUMO

BACKGROUND: Nowadays, stroke is a leading cause of disability in adults. Assessment of motor performance has played an important role in rehabilitation for post stroke patients. Therefore, it is quite important to develop an automatic assessment system of motor function. OBJECTIVE: The purpose of this study is to assess the performance of the single task upper-limb movements quantitatively among stroke survivors. METHODS: Eleven normal subjects and thirty-five subjects with stroke were involved in this study. The subjects, who were wearing the micro-sensor motion capture system, performed shoulder flexion in a sitting position. The system recorded three-dimensional kinematics data of limb movements in quaternions. By extracting the significant features from these data, we built a linear model to acquire the functional assessment score (FAS). RESULTS: All of the kinematics features have a significant statistical difference (P < 0.05) between patients and healthy people, while the feature values have a high correlation with Fugl-Meyer (FM) scores (r > 0.5, p < 0.05), indicating that these features are able to reflect the level of motion impairment. Furthermore, most samples of the linear model locate in the confidence interval after regression, with the residual approaching a normal distribution. These results show that the FAS is capable of motor function assessment for stroke survivors. CONCLUSION: These findings represent an important step towards a system that can be utilized for precise single task motor evaluation after stroke, applicable to clinical research and as a tool for rehabilitation.


Assuntos
Transtornos Motores/diagnóstico , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologia , Retroalimentação Sensorial , Humanos , Transtornos Motores/etiologia , Acidente Vascular Cerebral/complicações
12.
Zhonghua Er Ke Za Zhi ; 53(10): 747-53, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26758110

RESUMO

OBJECTIVE: To explore the application value of next generation sequencing (NGS) in the diagnosis of mitochondrial disorders. METHOD: According to mitochondrial disease criteria, genomic DNA was extracted using standard procedure from peripheral venous blood of patients with suspected mitochondrial disease collected from neurological department of Beijing Children's Hospital Affiliated to Capital Medical University between October 2012 and February 2014. Targeted NGS to capture and sequence the entire mtDNA and exons of the 1 000 nuclear genes related to mitochondrial structure and function. Clinical data were collected from patients diagnosed at a molecular level, then clinical features and the relationship between genotype and phenotype were analyzed. RESULT: Mutation was detected in 21 of 70 patients with suspected mitochondrial disease, in whom 10 harbored mtDNA mutation, while 11 nuclear DNA (nDNA) mutation. In 21 patients, 1 was diagnosed congenital myasthenic syndrome with episodic apnea due to CHAT gene p.I187T homozygous mutation, and 20 were diagnosed mitochondrial disease, in which 10 were Leigh syndrome, 4 were mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome, 3 were Leber hereditary optic neuropathy (LHON) and LHON plus, 2 were mitochondrial DNA depletion syndrome and 1 was unknown. All the mtDNA mutations were point mutations, which contained A3243G, G3460A, G11778A, T14484C, T14502C and T14487C. Ten mitochondrial disease patients harbored homozygous or compound heterozygous mutations in 5 genes previously shown to cause disease: SURF1, PDHA1, NDUFV1, SUCLA2 and SUCLG1, which had 14 mutations, and 7 of the 14 mutations have not been reported. CONCLUSION: NGS has a certain application value in the diagnosis of mitochondrial diseases, especially in Leigh syndrome atypical mitochondrial syndrome and rare mitochondrial disorders.


Assuntos
DNA Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Mitocondriais/diagnóstico , Análise de Sequência de DNA , Criança , Homozigoto , Humanos , Doença de Leigh , Encefalomiopatias Mitocondriais , Mutação , Atrofia Óptica Hereditária de Leber , Fenótipo , Mutação Puntual
13.
Zhonghua Er Ke Za Zhi ; 50(12): 885-9, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23324141

RESUMO

OBJECTIVE: To study the clinical and laboratory features and diagnosis of the patient with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis in children. METHOD: The data of clinical feature, laboratory findings, and radiological manifestation were reviewed and analyzed. RESULT: Of the 7 patients, 4 were female and 3 were male. The age of onset was from 6.6 to 15.5 years (average 9.5 years). The onset of 4 cases started with convulsion. Six cases had seizures which was difficult to control by antiepileptic drugs. All patients had psychiatric symptoms and speech disorder. Six cases had different levels of decreased consciousness and dyskinesias. 6 cases had autonomic nerve instability, and 7 cases developed sleep disorders. The results of MRI examination were normal in all patients. The EEG of most patients showed focal or diffuse slow waves. Six cases had oligoclonal bands. All cases were confirmed to have the disease by detection of anti-NMDA receptor antibodies. No tumor was detected in any of the patients. All patients received immunotherapy. CONCLUSION: Anti-NMDAR encephalitis is a severe but treatable disorder that frequently affects children and adolescents. Pediatric patients had clinical manifestations similar to those of adult patients. But children have a lower incidence of tumors and hypoventilation also occurs less frequently in children. Most of children had a good prognosis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Autoanticorpos/sangue , Imunoterapia/métodos , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Autoanticorpos/líquido cefalorraquidiano , Sistema Nervoso Autônomo/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Eletroencefalografia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtornos dos Movimentos/etiologia , Radiografia , Estudos Retrospectivos , Convulsões/etiologia
14.
Pediatr Neurol ; 40(4): 277-81, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19302940

RESUMO

This study assessed potential etiologies of arterial ischemic stroke and hemorrhagic stroke among children of Mainland China. From January 1996-June 2006, 251 patients with consecutive childhood stroke (aged 1 month through 16 years) were admitted to Beijing Children's Hospital. Arterial ischemic stroke accounted for the majority of cases (62.5%). Idiopathic stroke (32.5%) was more common than cardiac stroke (8.9%), vascular or arteriopathic stroke (21.0%), hematologic disorder-associated stroke (10.8%), and other etiologies (26.8%). Vitamin K deficiency was a major etiology in 72 of 94 hemorrhagic strokes (76.6%), most of which occurred in breastfeeding infants (80.6%) and those who received no vitamin K after birth (73.6%). Arteriovenous malformation (6.4%) was a frequent etiology in the remaining hemorrhagic stroke cases. We found that ischemic stroke in children is more common than hemorrhagic stroke, and many cases of ischemic stroke are idiopathic. Vitamin K deficiency was a major etiology in these young infants who experienced hemorrhagic stroke.


Assuntos
Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Adolescente , Isquemia Encefálica/etiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Malformações Vasculares do Sistema Nervoso Central/complicações , Malformações Vasculares do Sistema Nervoso Central/epidemiologia , Hemorragia Cerebral/etiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/epidemiologia
16.
Pediatr Neurol ; 38(3): 186-90, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18279753

RESUMO

The aim of this study was to review cases of pediatric arterial ischemic stroke among Chinese subjects and thereby evaluate risk factors, clinical and neuroimaging features, and treatment, to establish a reasonable guideline for assessment and management of the disease. Between 1996 and 2006, 157 children (male:female ratio, 1.4:1) with arterial ischemic stroke were identified at Beijing Children's Hospital. The median age at stroke was 32 months (range, 4-192). Among patients with determined etiology, infections (12.1%), moyamoya disease (12.1%), and trauma (10.8%) were the most common. In 51 patients, there were no obvious risk factors (32.5%). Hemiplegia was the most common presenting feature (81.5%). The region of left middle cerebral artery was most frequently affected (36.3%), followed by the right middle cerebral artery (29.9%). Of the 157 patients, 56 were treated by intravenous thrombolytic agents (35.7%), all but one of them successfully (the one exception involving hemorrhagic complication). Randomized controlled trials are needed to establish primary prevention, acute treatment, and secondary prevention of pediatric ischemic stroke.


Assuntos
Isquemia Encefálica/complicações , Pediatria , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Feminino , Hemiplegia/etiologia , Humanos , Lactente , Masculino , Artéria Cerebral Média/patologia , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etnologia , Terapia Trombolítica/métodos
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