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Objective: To analyze the clinical features of anti-neurofascin-155 (NF155) antibody positive autoimmune nodopathy in children. Methods: This was a case series study. A total of 6 children who were diagnosed accurately as anti-NF155 antibody positive autoimmune nodopathy by cell immunofluorescence assay at the Children's Hospital of Fudan University from January 2020 to December 2023 were collected. This study retrospectively analyzed 6 pediatric children's clinical manifestations, laboratory and electrophysiological examination results, and treatment outcomes. Results: Among 6 children with anti-NF155 antibody positive autoimmune nodopathy, there were 4 boys and 2 girls. The onset age of 6 children ranged from 3 years and 8 months to 12 years. All 6 children had extremity weakness (more severe in the distal and the lower extremities than in the upper extremities), 5 children had sensory deficits such as numbness or pain in the extremities, 4 children had tremors and ataxia, 3 children had cranial nerve involvement. Among the 6 children, 4 children had protein-cell separation in cerebrospinal fluid examinations. Among the 6 children, 1 child had central nervous system demyelination, the brain magnetic resonance imaging showed multiple abnormal signals in the bilateral cerebral hemispheres. Four children showed motor and sensory nerve damage in electrophysiological examination, and 2 children only showed motor nerve damage. Three children showed myelin and axonal damage, and 3 children only showed axonal damage. Among the 6 children, 5 children were treated with intravenous immunoglobulin and steroids. Among them, 2 children underwent plasma exchange due to poor efficacy, and subsequently, rituximab was added. There was 1 child changed the treatment with olfatomumab since the symptoms did not significantly improve after using rituximab. After treatment for 4-15 months, 2 children had no clinical symptoms, 1 child had improvement in clinical symptoms, 2 children had no significant improvement in clinical symptoms, and 1 child who did not receive the immunotherapy had no significant change in clinical symptoms. Conclusions: Anti-NF155 antibody positive autoimmune nodopathy in children presents with varying degrees of clinical manifestations. It is mainly characterized by extremity weakness, numbness and pain, often accompanied bytremorsand ataxia. Some pediatric patients may also have central nervous system demyelination. Cerebrospinal fluid and electrophysiological examination are important auxiliary examination methods. If steroid therapy is not effective, plasma exchange and rituximab treatment should be used as soon as possible.
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Autoanticuerpos , Factores de Crecimiento Nervioso , Humanos , Femenino , Masculino , Niño , Estudios Retrospectivos , Preescolar , Moléculas de Adhesión Celular , Imagen por Resonancia Magnética , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/tratamiento farmacológico , Enfermedades Autoinmunes del Sistema Nervioso/inmunologíaRESUMEN
Objective: To explore the clinical and imaging features of acute encephalopathy with biphasic seizures and late reduced diffusion(AESD) in children. Methods: For the case series study, 21 children with AESD from Peking University First Hospital, Provincial Children's Hospital Affiliated to Anhui Medical University, Children's Hospital of Fudan University, and Shanxi Children's Hospital who were diagnosed and treated from October 2021 to July 2023 were selected. Clinical data were collected to summarize their clinical information, imaging, and laboratory tests, as well as treatment and prognostic characteristics. Descriptive statistical analysis was applicated. Results: Of the 21 cases with AESD, 11 were males and 10 were females, with the age of onset of 2 years and 6 months (1 year and 7 months, 3 years and 6 months). Of the 21 cases, 18 were typical cases with biphasic seizures. All typical cases had early seizures within 24 hours before or after fever onset. Among them, 16 cases had generalized seizures, 2 cases had focal seizures, and 7 cases reached the status epilepticus. Of the 21 cases, 3 atypical cases had late seizures in biphasic only. The late seizures in the 21 cases occurred on days 3 to 9. The types of late seizures included focal seizures in 12 cases, generalized seizures in 6 cases, and both focal and generalized seizures in 3 cases. Diffusion-weighted imaging (DWI) test on days 3 to 11 showed reduced diffusion of subcortical white matter which was named "bright tree sign" in all cases. The diffuse cerebral atrophy predominantly presented in the front-parietal-temporal lobes was found in 19 cases between day 12 and 3 months after the onset of the disease. Among 21 cases, 20 had been misdiagnosed as autoimmune encephalitis, central nervous system infection, febrile convulsions, posterior reversible encephalopathy syndrome, acute disseminated encephalomyelitis, and hemiconvulsion-hemiplegia-epilepsy syndrome. All the cases received high-dose gammaglobulin and methylprednisolone pulse therapy with poor therapeutic effect. By July 2023, 18 cases were under follow-up. Among them, 17 cases were left with varying degrees of neurologic sequelae, including 11 cases with post-encephalopathic epilepsy; 1 recovered completely. Conclusions: AESD is characterized by biphasic seizures clinically and "bright tree sign" on DWI images. Symptomatic and supportive treatments are recommended. The immunotherapy is ineffective. The prognosis of AESD is poor, with a high incidence of neurological sequelae and a low mortality.
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Encefalopatías , Síndrome de Leucoencefalopatía Posterior , Convulsiones Febriles , Estado Epiléptico , Masculino , Femenino , Niño , Humanos , Lactante , Preescolar , Síndrome de Leucoencefalopatía Posterior/complicaciones , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Encefalopatías/diagnóstico por imagen , Convulsiones Febriles/diagnóstico por imagenRESUMEN
In this study we present 2 surgical models of hypothyroidism in male Wistar rats (n=80) based on total thyroidectomy. Animals weighing 180-200 g were randomly divided into sham-operated group and 2 experimental groups. Thyroidectomy was performed by 2 different methods: primary ligation of either thyroid artery (TE-I) or vein (TE-II). The success of the model was verified through general postoperative conditions, serum hormone levels, histological study, and neck ultrasound. Hypothyroidism was successfully reproduced in both TE-I and TE-II models. TE-I was characterized by lower intra- and post-operative mortality, while TE-II provided better surgical exposure to the key anatomical sites.
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Hipotiroidismo , Ratas , Animales , Masculino , Ratas Wistar , Hipotiroidismo/patología , TiroidectomíaRESUMEN
Objective: To investigate the clinical characteristics and genetic features of congenital myasthenic syndrome (CMS) related to SLC25A1 gene variant. Methods: The clinical data of two SLC25A1 gene variant related CMS patients treated at the Children's Hospital of Fudan University between January 2015 and June 2019 were analyzed retrospectively. A literature search with "SLC25A1" and "congenital myasthenic syndrome" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to June 2020). The clinical characteristics and genetic features of congenital myasthenic syndrome related to SLC25A1 gene variant were summarized. Results: Two patients were all males, aged 9 years and 2 years respectively and the onset age was in infancy. In addition to typical CMS symptoms (fatigable muscular weakness, including bilateral ptosis, strabismus, masticatory weakness, low voice and limb weakness), the two patients both had developmental delay along with metabolic abnormalities (elevated urinary 2-ketoglutarate (2-KG), elevated lactic acid levels or 2-hydroxyglutaric aciduria). Trio whole-exome sequencing (WES) revealed two novel pathogenic variants of SLC25A1(c.628C>T, p.R210X; c.145G>A, p.V49M) in case 1 and (c.145G>A, p.V49M; microdeletion) in case 2. After literature search, 15 cases in 3 English articles were found, which made up the complete case data of 17 patients (including these 2 cases). Seventeen patients had very early onset with the age of 2 years. Mild intellectual disability was recorded in 9 patients, and mild developmental delay was observed in one patient. 5 SLC25A1 gene variants (three missense, one nonsense and one microdeletion) were identified in these cases. Twelve patients from 6 pedigrees harbored one same variant (c.740G>A, p.R247Q) and two cases had the other variant (c.145G>A, p.V49M). Conclusions: Patients diagnosed with SLC25A1 related CMS have very early onset, and most of them have intellectual disability or developmental delay. Part of patients had metabolic abnormalities. The variants (c.740G>A, p.R247Q and c.145G>A, p.V49M) are recurrent.
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Encefalopatías Metabólicas Innatas , Síndromes Miasténicos Congénitos , Transportadores de Anión Orgánico , Niño , Preescolar , China , Humanos , Masculino , Proteínas Mitocondriales/genética , Mutación , Síndromes Miasténicos Congénitos/genética , Linaje , Estudios RetrospectivosRESUMEN
Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). Methods: Clinical data of 19 children with GLUT1 DS admitted to Children's Hospital of Fudan University, Tianjin Children's Hospital, Shenzhen Children's Hospital, Children's Hospital of Nanjing Medical University and Jiangxi Provincial Children's Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results: Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT. Conclusions: The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.
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Errores Innatos del Metabolismo de los Carbohidratos , Dieta Cetogénica , Proteínas de Transporte de Monosacáridos/deficiencia , Errores Innatos del Metabolismo de los Carbohidratos/dietoterapia , Errores Innatos del Metabolismo de los Carbohidratos/genética , Niño , Preescolar , Femenino , Transportador de Glucosa de Tipo 1/genética , Humanos , Lactante , Masculino , Proteínas de Transporte de Monosacáridos/genética , Estudios RetrospectivosRESUMEN
Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.
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Trastorno por Déficit de Atención con Hiperactividad , Trastornos de Tic , Síndrome de Tourette , Clorhidrato de Atomoxetina , Niño , Comorbilidad , Femenino , Humanos , Masculino , Trastornos de Tic/tratamiento farmacológico , Trastornos de Tic/epidemiología , Síndrome de Tourette/tratamiento farmacológico , Síndrome de Tourette/epidemiologíaRESUMEN
Objective: To summarize the clinical and genetic features of ß-propeller protein-associated neurodegeneration (BPAN). Methods: The clinical data of 17 patients with BPAN with WDR45 gene variants were retrospectively collected at Children's Hospital of Fudan University, Peking University First Hospital, Capital Institute of Pediatrics, Shengjing Hospital of China Medical University and Shanghai Children's Hospital from June 2016 to December 2018, and their clinical manifestations, electroencephalogram, neuroimaging and genetics were analyzed. Results: Seventeen cases (13 females, 4 males), aged 1.1-8.8 years, were included. The median age of seizure onset was 14.5 months, from 3 months to 24 months of age, manifested with epileptic spasm in 6 cases and focal seizures in 5 cases. Eight patients had only one seizure type and 8 patients had two or more seizure types. Nine patients had complete remission of seizures. All 16 patients with seizures had developmental delay before the seizure onset, of whom 13 patients had moderate to severe seizures. The brain magnetic resonance imaging (MRI) was abnormal in 13 patients, including cerebral atrophy (10 cases) and thinning of the corpus callosum (9 cases). The brain magnetic susceptibility weighted imaging (SWI) in preschool stage showed prominent T2 hypointense signals in bilateral globus pallidus and brainstem ventral in two cases. Five seizure types (spasm, focal, absence, myodonic and generalized tonic clonic seizures)were found on ictal electroencephalogram(EEG) recordings. Compared to female patients(17(6-24) months of ege), male cases had earlier seizure onset (3, 4, 5, 18 months of age) . All patients had de novo variations in WDR45(6 nonsense, 4 frameshift, 3 missense and 4 splicing variations), with hemizygous variants in 3 males, mosaic variants in a male and heterozygous variants in 13 females, within which 5 variations had not been reported (c.977-1C>T,c.976+1G>C,c.10C>T,c.806del and c.110T>C). Conclusions: The patients with BPAN have profound developmental delay and are vulnerable to seizures. The male patients with BPAN tend to have more severer clinical phenotype than females. Early brain SWI could facilitate the timely diagnosis of this disease.
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Proteínas Portadoras/genética , Epilepsia/genética , Enfermedades Neurodegenerativas/genética , China , Electroencefalografía , Epilepsia/diagnóstico , Femenino , Humanos , Lactante , Masculino , Enfermedades Neurodegenerativas/diagnóstico por imagen , Estudios Retrospectivos , ConvulsionesRESUMEN
Objective:The aim of this study is to detect differentially methylated genes to allergic rhinitis (AR) based on methylation chip, and to analyze the relationship between DNA methylation and AR.Method:Illumina methylation chip were made by normal inferior turbinate mucous tissue obtained from patients(n=19) and healthy individuals(n=11). Detection of differential the sites of methylated genes, Gene Ontology enrichment, KEGG pathway enrichment database and literature search were used to analysis.Result:There were 94 aberrant methylation sites in patients with AR, including 51 hypermethylation sites (e.g. ST7,LCE2D,ATRIP genes) and 43 hypomethylation sites (e.g. PIK3CG, TLR6, IL-4 genes). The results of Gene Ontology enrichment and KEGG pathway enrichment indicates the DNA methylation has relative trend with AR, and DNA methylation of ST7, LCE2D, PIK3CG genes may be associated with AR, but the results of GO analysis and KEGG analysis were statistically significant. Moreover, literature search prompts that DNA methylation of TLR6 gene and IL-4 gene may be associated with AR.Conclusion:Varying degrees of methylated genes from inferior turbinate mucous tissue based on high-flux methylation chip hint gene methylation is an important cause of AR. The relationship between them needs further verification.
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AbstractObjective:To review the demographic characteristics and canalith repositioning efficacy in 907 patients with typical benign paroxysmal positional vertigo(BPPV). Method: The demographic characteristics of 907 patients with typical BPPV were statistically analyzed. According to the type of BPPV, patients were treated with the appropriate repositioning maneuver, and the clinical efficacy of repositioning maneuver was analyzed and summarized. Result: Nine hundred and seven patients of BPPV with typical nystagmus were elected in this study. 585 out of 907 were female and 322 out of were male, and the mean age was 53.10±14.25(13 to 89) years. The lesion located to the posterior semiCIrcular canal was 489 patients(53.9%), horizontal semiCIrcular canal was 312 patients(34.4%), anterior semiCIrcular was 63 patients(6.9%), and multiple semiCIrcular was 43 patients(4.8%). According to Kaplan-Meier survival analysis curve, the median cure time for the modified Semont and Epley repositioning maneuver in PC-BPPV groups was 3 days, and there was no significant difference in survival curves between the two repositioning maneuver. Meanwhile, the median cure time for Barbecue and Li horizontal canal quick repositioning maneuver groups was 3 days, and 1 day for Gufoni repositioning maneuver group in HC-BPPV groups. And there was no significant difference in survival curves among the three repositioning maneuver. In the AC-BPPV, 7 cases, 31 cases, 57 cases, 58 cases were cured with the Li anterior canal quick repositioning maneuver in the 1st day, the 3rd day, 1 week later, and 1 month later, and 5 cases lost to be follow-up. According to Kaplan-Meier survival analysis curve, the median cure time for the Li anterior canal quick repositioning maneuver in AC-BPPV groups was 3 days. Conclusion:Repositioning maneuver represents a simple, safe, rapid and effective approach to the treatment of BPPV. Therefore, repositioning maneuver should be choice for the BPPV treatment.
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OBJECTIVE: To observe the clinical efficacy of melatonin on acute organophosphorus pesticide poisoning (AOPP). PATIENTS AND METHODS: In this randomized control trial, a total of 59 AOPP patients with subsequent delirium were randomly divided into two groups, the melatonin group (n=29) and the placebo-controlled group (n=30). Patients in the melatonin group (n=29) underwent oral administration of melatonin in addition to the symptomatic treatment, while those in the placebo-controlled group took a placebo in addition to the symptomatic treatment. Before and 12 weeks after treatment, adverse events of participants in both groups were classified according to their scores in the assessment of the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-SI) scale, and Treatment Emergent Symptom Scale (TESS). RESULTS: The excellence rates of patients in the melatonin group and the placebo-controlled group were 82.75% and 30.00%, respectively (χ2 = 17.054, p < 0 .01). No adverse events were identified in all participants. CONCLUSIONS: Melatonin may serve as an effective drug in the treatment of AOPP-induced deliration.
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Delirio/tratamiento farmacológico , Melatonina/uso terapéutico , Intoxicación por Organofosfatos/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Anciano , Delirio/psicología , Femenino , Humanos , Masculino , Melatonina/efectos adversos , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks). Among them, five cases had no effect and two cases were seizure free recently. A case with GABRB3 (C.905A>G) had seizure controlled for 3 mouths. A case with ARX (C.700G>A) had seizure controlled for 6 mouths. Conclusion: The early onset epileptic spasm with unknown reason is highly related to genetic disorders. A variety of genetic mutations, especially new mutations were found. Genetic heterogeneity of epileptic spasm is obvious.
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Epilepsia/genética , Espasmos Infantiles/genética , Hormona Adrenocorticotrópica , Anticonvulsivantes/uso terapéutico , Variaciones en el Número de Copia de ADN , Electroencefalografía , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Estudios Prospectivos , Convulsiones , Espasmo , Espasmos Infantiles/tratamiento farmacológicoRESUMEN
Objective: To investigate the clinical features and genetic characteristics of patients with TBC1D24 gene mutations. Method: The clinical data of a patient with novel TBC1D24 compound heterozygous mutations from Children's Hospital of Fudan University were collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and Pubmed (up to April 2016) by using search terms "TBC1D24" "epilepsy" . The clinical features, electroencephalogram (EEG) and prognosis of the patients with TBC1D24 gene mutations were studied. Result: The patient was a boy with non-consanguineous healthy parents.He had an acute episode of focal continuous myoclonus lasting a few hours with consciousness preserved at the age of 3 months.Myoclonic jerks alternatively affected the eyelids, either the right or left limbs, sometimes triggered by fever or fatigue.The frequency was once 3-7 days.At the age of 6 months he was found to have myoclonus seizures with onset from a unilateral eyes lid and limb lasting 10 more minutes and subsequently affected four extremities or the trunk.They occurred once 3-4 months with perserved consciousness and lasted from several hours to up to ten more hours.They mostly disappeared during sleep.He had ataxia and mild mental retarding.Paroxysmal anomalies were not found on ictal traces.A novel compound heterozygous mutation of TBC1D24 gene, c. 730G>A, p.A244T and c. 1571G>C, p.R524P were found in the patient.Further study showed that c. 730G>A mutation was inherited from his father and c. 1571G>C from his mother. These two were not reported in public databases and predicted deleterious by Mutation Taster and polyphen-2.Literature relevant to TBC1D24 published all around the world was reviewed, no Chinese cases with TBC1D24 gene mutations had been reported. The total of 24 cases including the present case with TBC1D24 gene mutation were reported.Among them, 11 cases had compound heterozygous mutations and 13 cases had homozygous mutations.Ten mutations were identified, including 1 termination mutation, 1 frameshift mutation and 8 missense mutations. Conclusion: TBC1D24 gene mutational analysis should be performed on patients with early-onset focal continuous myoclonus, if the etiology was unclear.
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Proteínas Portadoras/genética , Epilepsias Mioclónicas/genética , Mutación Missense , Niño , Electroencefalografía , Epilepsia , Proteínas Activadoras de GTPasa , Homocigoto , Humanos , Lactante , Discapacidad Intelectual , Masculino , Proteínas de la Membrana , Proteínas del Tejido Nervioso , Espasmos InfantilesRESUMEN
BACKGROUND: Hypertrophic scars (HPSs) are characterized by excessive fibrosis associated with aberrant function of fibroblasts. Currently no satisfactory treatment has been developed. OBJECTIVES: To investigate the effect of baicalein on HPSs and its underlying mechanisms. METHODS: Baicalein was administered intradermally (10 µmol L(-1) in 100 µL sterile saline plus 10% dimethylsulfoxide) to mechanical-load-induced scars in mice once a day for 14 or 28 days. Histological and immunohistochemical studies were performed to evaluate scar hypertrophy and the function of fibroblasts. Human HPS-derived fibroblasts (HSFs) were determined by immunofluorescence study, collagen gel contraction assay and wound-healing assay. Also, protein expression of the transforming growth factor (TGF)-ß signalling pathway was detected using Western blotting. Lastly, a molecular docking study and kinase binding assay were conducted in search of the potential interaction between baicalein and activin receptor-like kinase (ALK)5. RESULTS: Baicalein treatment significantly attenuated HPS formation and collagen deposition in a mechanical-load-induced mouse model. Baicalein also inhibited the proliferation and activation of fibroblasts in vitro and in vivo. Furthermore, baicalein impaired the contractile and migration ability of HSFs. Protein expression investigation revealed that baicalein had an inhibitory effect on TGF-ß/Smad2/3 signalling. Such bioactivity of baicalein may result from its selective binding to the ATP-binding pocket of ALK5, as suggested by the molecular docking study and kinase binding assay. CONCLUSIONS: Baicalein could serve as a promising agent for treatment of HPSs and a selective ALK5 inhibitor.
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Antioxidantes/farmacología , Cicatriz Hipertrófica/tratamiento farmacológico , Fármacos Dermatológicos/farmacología , Flavanonas/farmacología , Proteína Smad2/antagonistas & inhibidores , Proteína smad3/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Adolescente , Adulto , Animales , Niño , Cicatriz Hipertrófica/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Adulto JovenRESUMEN
Reactive oxygen species (ROS) play a critical role in the pathogenesis of neuropathic pain, but few studies have examined the role of oxidative stress in the mirror-image neuropathic pain (MINP). The present study was to investigate the role of ROS in MINP caused by chronic compression of the dorsal root ganglion (DRG) (CCD) in a rat model. SD rats were randomly divided into sham group and CCD group. CCD was conducted to induce MINP. CCD rats were intraperitoneally injected with α-Phenyl-N-tert-butyl-nitrone (PBN) at 7 days after surgery. Paw withdrawal mechanical threshold (PWMT) was measured at -1, 1, 3, 5 and 7 days after surgery in sham group and CCD group, and at 8 time points after PBN injection. Rats were sacrificed at 3 and 7 days after surgery in sham group and CCD group and at 0.5 and 2 h after PBN injection, and the superoxide dismutase (SOD) and catalase activities, as well as hydrogen peroxide (H2O2) and malonaldehyde (MDA) contents were determined in the contralateral DRGs. Results showed bilateral PWMT reduced significantly in sham group and CCD group, but it returned to nearly normal level in sham group. MDA content, H2O2 content and SOD activity increased significantly, while catalase activity remained unchanged in CCD rats. PBN at 100 mg/kg significantly attenuated bilateral mechanical hyperalgesia accompanied by the improvement of oxidative stress in the contralateral DRGs. Our results demonstrate that ROS produced in the contralateral DRG are involved in the pathogenesis of CCD induced MINP, and ROS scavenger may be a promising drug for the therapy of MINP.