RESUMO
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.
Assuntos
Neuroblastoma , Transtornos da Motilidade Ocular , Síndrome de Opsoclonia-Mioclonia , Masculino , Criança , Humanos , Pré-Escolar , Prognóstico , Estudos Retrospectivos , Transtornos da Motilidade Ocular/complicações , Recidiva Local de Neoplasia , Síndrome de Opsoclonia-Mioclonia/diagnóstico , Síndrome de Opsoclonia-Mioclonia/tratamento farmacológico , Neuroblastoma/complicações , Neuroblastoma/diagnóstico , Neuroblastoma/terapia , AtaxiaRESUMO
A 53-year-old female patient complained of 1 week of bilateral visual blurring. She was previously diagnosed with metastatic melanoma of the inguinal lymph nodes and treated with the oral targeted drug vemurafenib. She exhibited aqueous flare in the left eye, and her fundus examination revealed optic disc swelling in the left eye and bilateral serious detachment of the retinal neuroepithelial layer. Fluorescein angiography showed multiple pinpoint hyperfluorescence leakage spots in the prometaphase and appeared as multilobular dye pooling in the late phase. We diagnosed her as Vogt-Koyanagi-Harada syndrome and gave glucocorticoid treatment for eyes. Oral vemurafenib was also taken intermittently under the guidance of an oncologist. After treatment, her bilateral vision improved, the anterior segment inflammation disappeared, and the retinal neuroepithelial layer reattached, with presence of the "sunset glow" fundus.
Assuntos
Melanoma , Síndrome Uveomeningoencefálica , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome Uveomeningoencefálica/tratamento farmacológico , Vemurafenib/efeitos adversos , Angiofluoresceinografia , Melanoma/tratamento farmacológico , Fundo de Olho , Transtornos da Visão/etiologiaRESUMO
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.
Assuntos
Epilepsias Mioclônicas , Epilepsia , Pré-Escolar , Eletroencefalografia , Epilepsia/genética , Humanos , Estudos Retrospectivos , Convulsões , Proteínas Ativadoras de ras GTPaseRESUMO
Objective: To investigate the clinical features and prognosis of pediatric autoimmune encephalitis associated with anti-glutamic acid decarboxylase 65 (GAD65) antibody. Methods: Clinical data of 2 patients diagnosed as autoimmune encephalitis associated with anti-GAD65 antibody at Department of Neurology, Beijing Children's Hospital in 2019 were analyzed retrospectively. A literature search with "anti-GAD65 antibody""encephalitis""epilepsy" or "cerebellar ataxia" as key words was conducted at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform and PubMed (up to January 2020). The clinical features and prognosis of pediatric cases with complete clinical data were retrieved and summarized. Results: Two patients with positive anti-GAD65 antibody of serum and cerebrospinal fluid were both females. The onset age of case 1 was 57 months and her main clinical manifestations were fever and unconsciousness. The cranial magnetic resonance imaging (MRI) showed diffuse T2 weighted imaging (T2WI) abnormal signals, and the electroencephalogram (EEG) showed slow waves. The onset age of case 2 was 80 months and her main clinical manifestations of were recurrent focal seizures, memory loss, and headache. The MRI showed high T2WI signal in bilateral hippocampus, and the EEG showed abnormal discharge involving the temporal area. Both cases were treated with methylprednisolone and intravenous immunoglobulin, the short-term symptoms of them were both improved. They were followed up for 6 months and 1 year respectively, the case 1 recovered completely, and the case 2 still had focal seizures. Six English reports which included 6 cases were retrieved. Together with these 2 cases, a total of 8 cases were analyzed. The clinical symptoms included seizures (6 cases), memory loss (4 cases), loss of consciousness (3 cases), behavioral abnormalities (3 cases), cognitive impairment (2 cases), headache (2 cases), autonomic symptoms (1 case), ataxia (1 case), dysphagia (1 case), and aphasia (1 case). There were 5 cases with cranial MRI abnormalities in the acute phase or sub-acute phase, of whom 3 cases had the limbic system involvement, and 2 cases were mainly had extra limbic area involvement. Three cases had hippocampal atrophy or sclerosis during follow-up. All 8 patients were treated with immunotherapy. After immunotherapy, all patients had short-term improvement. Follow-up for 6 months to 6 years showed that 3 cases with extra limbic encephalitis improved to baseline levels, and 5 limbic encephalitis cases had poor outcomes, including 1 death and 4 cases still had focal epilepsy. Conclusions: Pediatric anti-GAD65 antibody associated autoimmune encephalitis is a rare but treatable disease, including limbic encephalitis and extra limbic encephalitis. The most common clinical manifestations are seizures and memory impairment. Early diagnosis and immunotherapy can improve the symptoms in a short time. But patients with limbic encephalitis often had refractory epilepsy in the chronic phase, and have a poor long-term outcome.
Assuntos
Encefalite , Doença de Hashimoto , Autoanticorpos , Criança , China , Encefalite/diagnóstico , Feminino , Doença de Hashimoto/diagnóstico , Humanos , Lactente , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Objective: To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children. Methods: Patients who were hospitalized in Beijing Children's Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies. Results: Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10(6)/L to 186×10(6)/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil. Conclusions: Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.
Assuntos
Encefalite , Autoanticorpos , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos , ConvulsõesRESUMO
Objective: To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS). Methods: The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children's Hospital from January 2011 to April 2019 were analyzed retrospectively. Results: A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases). Conclusions: MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos , Doenças Autoimunes , Glicoproteína Mielina-Oligodendrócito , Adolescente , Doenças Autoimunes/diagnóstico , Criança , Feminino , Humanos , Masculino , Glicoproteína Mielina-Oligodendrócito/imunologia , Recidiva Local de Neoplasia , Receptores de Aminoácido , Estudos Retrospectivos , SíndromeRESUMO
Objective: To summarize the clinical and genetic characteristics of children with mitochondrial epilepsy. Methods: Clinical data of 62 children who were clinically and genetically diagnosed with mitochondrial epilepsy by the Department of Neurology, Beijing Children's Hospital from October 2011 to December 2018 were analyzed retrospectively, and the control of epilepsy was followed up. T test or χ(2) test were used to analyze the related factors affecting the prognosis of epilepsy between the effective group and the ineffective group. Results: Of the 62 patients, 33 were male and 29 were female. The age of onset was 3.38 (0-12.00) years; for the type of seizures, 68% (42/62) of the patients had focal seizures, generalized or secondary generalized tonic-clonic seizures were seen in 32% (20/62), myoclonic seizures in 23% (14/62), spastic seizures in 7 cases, tonic seizures in 4 cases, absence seizure, atonic seizure and clonic seizure in 1 case each; 16 cases (26%) had status epilepticus, of whom 6 cases had epilepsia partialis continua; 52% (32/62) had 2 or more types of seizures. The clinical phenotypes were mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) in 29 cases, Leigh syndrome (LS) in 11 cases, combined oxidative phosphorylation deficiency in 6 cases, myoclonus epilepsy with ragged-red fibers in 5 cases, Alpers syndrome in 4 cases, pontocerebellar hypoplasia type 6 and mitochondrial DNA depletion syndrome 9 in 2 cases each, mitochondrial complex â deficiency nuclear type 20, progressive cavitating leukoencephalopathy, and biotinidase deficiency in 1 case each. Of the 62 cases, 40 cases (65%) had mitochondrial DNA (mtDNA) variations, of which 26 cases had m.3243A>G variants, 6 cases had m.8344A>G variants, and 3 cases had m.8993T>G/C variants, m.3271T>C, m.3481G>A, m.3946G>A, m.13094T>C, m.14487T>C variant was in 1 case each; nuclear DNA (nDNA) variations were identified in 22 cases (35%), of which 7 cases carrying variations in mitochondrial ammonia acyl tRNA synthetase coding gene, mutations in POLG and the gene encoding complex â were in 4 cases each, variations in SUCLG1 and SDHA genes were in 2 cases each, and variations in PDHA1, BTD and TRIT1 genes were in 1 case each. Forty-three patients were followed up, and the follow-up time was 20 (3-84) months. According to the follow-up results, the anti-epilepsy treatment was effective in 19 cases (44%) and ineffective in other 24 cases (56%). The onset age of the effective group was 3.42 (0-11.50) years and that of the ineffective group was 0.92 (0-9.50) years. The onset duration of the effective group was 0 (0-7.00) years and that of the ineffective group was 0 (0-4.83) years. There was no significant difference between the effective group and the ineffective group (t=1.662, 0.860; P=0.104, 0.395). In the effective group and the ineffective group, 12 cases and 9 cases used less than 2 kinds of antiepileptic drugs, 7 cases and 15 cases used more than or equal to 2 kinds of antiepileptic drugs, 13 and 15 cases had first epilepsy, 6 and 9 cases had non-first epilepsy, 14 and 11 cases had mtDNA variation, 5 and 13 cases had nDNA variation, respectively. There was no significant difference between the two groups (χ(2)=2.794, 0.164, 3.380; P=0.095, 0.686, 0.066). Conclusions: The types of seizures with mitochondrial epilepsy in children varied, with focal motor seizures being the most common, followed by generalized or secondary generalized tonic-clonic seizures. Most children have more than two types of seizures. MELAS is the most common clinical phenotype, followed by LS; mtDNA variation is the dominant gene variation, of which m.3243A>G variation is the most common hotspot variation, followed by gene variation encoding mitochondrial aminoacyl tRNA synthase.
Assuntos
Epilepsia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Doenças Mitocondriais/diagnóstico por imagem , Anticonvulsivantes/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Epilepsia/genética , Feminino , Humanos , Masculino , Doenças Mitocondriais/genética , Fenótipo , Estudos Retrospectivos , ConvulsõesRESUMO
Objective: To characterize fever-induced paroxysmal weakness and encephalopathy (FIPWE) caused by ATP1A3 gene pathogenic variant. Methods: Phenotypic and genotypic characteristics of 4 FIPWE patients (3 boys and 1 girl), who were ascertained from October 2016 to March 2018 in Beijing Children's Hospital due to ATP1A3 heterozygous variants, were retrospectively analyzed. The whole exsome sequencing was used for genetic testing. Results: The onset ages of 4 patients were 2 years and 9 months, 2 years and 4 months, 8 months, 2 years and 5 months respectively. The episode ranged from 1 to 3 times, and at 3 months to 2 years and 10 months intervals. All 4 patients had symptoms of limb weakness and encephalopathy, accompanied with mild to severe ataxia or athetosis. The tendon reflex was absent in all patients, and the Babinski's sign was positive. Three patients had dysphagia and 3 patients had slurred speech. Three patients had abnormal eye movements, including strabismus and opsoclonus. None of the 4 patients exhibited visual impairment, auditory impairment or talipes cavus. The duration of acute phase ranged from 1 week to 3 months. In 3 relapsing patients, symptoms became progressively worse, with relapses occurring frequently and recovery being more difficult, and various sequelae were found after the last relapse. All patients carried heterozygous variant in ATP1A3 gene. The missense variants result in the substitution of an arginine residue at position 756. Three variants were identified, including C. 2267G > T (p. R756L) (1 case), C. 2266C > T (p. R756C) (2 cases), and C. 2267G > A (p. R756H) (1 case). Three were de novo and one inherited from his father, but the grandparents did not carry the variant. All variants were reported as pathogenic. Conclusions: FIPWE is one of new clinical phenotypes of ATP1A3 spectrum disease and most cases are sporadic. The missense variants result in the substitution of an arginine residue at position 756. This report provided insights into the phenotype-genotype association in patients with FIPWE caused by pathogenic variants of ATP1A3.
Assuntos
Encefalopatias/etiologia , Febre/complicações , Febre/genética , Debilidade Muscular/complicações , Mutação/genética , ATPase Trocadora de Sódio-Potássio/genética , Criança , Pré-Escolar , Feminino , Testes Genéticos , Genótipo , Humanos , Masculino , Fenótipo , Estudos RetrospectivosRESUMO
Objective: To explore the phenotype and genotype of mitochondrial DNA depletion syndromes (MDS) in Chinese children. Methods: The clinical and genetic data of 12 MDS patients (8 were boys and 4 were girls) diagnosed in the Department of Neurology in Beijing Children's Hospital, Capital Medical University from October 2010 to April 2018 were retrospectively collected and analyzed. Results: The developmental milestones were normal or mildly retardated before disease onset. The age of onset ranged from 0 to 2.9-year-old. Most cases developed postnatal or after infection. The most common initial symptoms were feeding difficulty, seizure, muscle weakness, psychomotor regression and hepatic dysfunction. At the last evaluation, all the patients had developmental retardation, failure to thrive, muscle weakness, and dysphagia. Other clinical features were weight loss (9 cases), hearing impairment (7 cases), ptosis (6 cases), seizure (5 cases), dyspnea (4 cases), visual impairment (1 case), hirsutism (1 case), lactic acidosis (7 cases), elevated hepatic enzymes (4 cases) and creatine kinase (2 cases), elevated protein in cerebrospinal fluid (3 cases), abnormalities on screening for inborn error of metabolism (10 cases) and brain magnetic resonance imaging (MRI) (10 cases), abnormal electromyogram (including neurogenic or myogenic injury) (5 cases). Five patients died of infection or multiple organ failure. A total of 18 novel mutations presented below were detected in these patients. Among the 6 cases of encephalomyopathy, there were 3 with SUCLG1 mutation (c. 916G>T, c. 619T>C, c. 980dupT were novel), 2 with SUCLA2 mutation (c. 851G>A, c.971G>A were novel), and one with RRM2B mutation (c.456-2A>G, c.212T>C were novel). All the cases of hepatic encephalopathy all had POLG mutations (c. 3151G>A, c. 2294C>T, c. 2858G>C, c. 680G>A and c. 150_158delGCAGCAGCA were novel). Two cases of infantile-onset spinocerebellar ataxia had TWNK mutations (c. 1163C>T, c. 1319T>C, c. 1388G>A and c. 257_258delAG were novel). One case of myopathy had TK2 mutations (c.557C>G and c.341A>T were novel). Conclusions: The clinical and genetic features of MDS were heterogeneous. Eighteen novel mutations in six MDS related genes were reported, which expanded the genetic spectrum of MDS in Chinese children.
Assuntos
DNA Mitocondrial/genética , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Succinato-CoA Ligases , Povo Asiático , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/fisiologia , Fenótipo , Estudos Retrospectivos , SíndromeRESUMO
Objective: To summarize the detailed clinical characteristics and genetic features of benign infantile epilepsy with PRRT2 mutation, in order to improve the understanding of the disease. Methods: The clinical data and genetic results of 40 benign infantile epilepsy patients with PRRT2 mutation who were diagnosed and treated in the neurology department of National Center for Children's Health (Beijing) , Beijing Children's Hospital affiliated to Capital Medical University from January 2002 to October 2017 and their affected family members were analyzed. Results: Forty benign infantile epilepsy patients were recruited for this study, with 18 males and 22 females. The age at onset ranged from 3 to 15 months (median: 4.6 months). All patients presented focal seizures with or without secondary generalization. Decreased responsiveness, eyes stare and cyanosis were commonly observed. A cluster of seizures was observed in 20 patients at the beginning of the disease, but interictal clinical conditions were normal. Interictal electroencephalograms were normal in 32 cases but 8 cases showed small amount scattered spike and spike wave. Two patients developed paroxysmal kinesigenic dyskinesia in 30 months and 12 years respectively after the cessation of the seizure. Thirty-four affected pedigree members had a history of paroxysmal episodes in 24 families, including 19 individuals of infantile afebrile convulsion, 6 individuals of paroxysmal kinesigenic dyskinesia during childhood or adulthood, 8 individuals of infantile convulsion and paroxysmal kinesigenic dyskinesia during adulthood, one individual of infantile febrile convulsion. The follow-up time ranged from 6 months to 15 years. Thirty-six patients were treated with antiepileptic drugs and their seizures were easy to control. Four patients stayed seizure free without medication (all <2 years). Seizure stopped in 24 patients within 1 year of age, in 10 patients stopped during 12-24 months and in 2 patients stopped during 24-36 months. All cases had PRRT2 mutations, 7 cases of a complete PRRT2 deletion, 33 cases of PRRT2 heterozygous mutations consisted of 28 frameshift mutations and 5 missense mutations. Of these heterozygous mutations, 30 cases were hereditary mutations while 3 were de novo mutations. Nine family members harbored the same PRRT2 mutations without any symptom. Conclusions: Benign infantile epilepsy with PRRT2 mutation is characterized by early onset of seizure mostly before 6 months, focal seizures with or without secondary generalization, a high incidence of a cluster of seizures, rapid resolution of seizure by antiepileptic drugs and cessation of seizure mostly before 2 years of age. Partial patients may develop paroxysmal kinesigenic dyskinesia increasing with age. Most PRRT2 gene mutations are heterozygous mutations, and a few are the overall deletion of PRRT2 gene.
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Epilepsia Neonatal Benigna , Proteínas de Membrana , Proteínas do Tecido Nervoso , Epilepsia , Epilepsia Neonatal Benigna/genética , Feminino , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética , LinhagemRESUMO
Objective: To investigate the clinical features and diagnostic bases of childhood leukoencephalopathy with cerebral calcifications and cysts (LCC). Methods: The clinical data involving manifestations and laboratory examinations of 4 children with LCC admitted to Beijing Children's Hospital Affiliated to Capital Medical University from 2012 to 2017 were retrospectively summarized. Each patient had a follow-up visit ranging from 4 months to 5 years and 9 months after initial examination. Results: Patients consisted of 2 males and 2 females, whose age of onset was respectively 2 years and 9 months, 6 years and 2 months, 7 years and 10 months, and 5 years and 1 month. The main clinical symptoms of these cases included headache, dizziness, partial seizure and claudication, and two of these cases had insidious onset. Cerebral calcifications and cysts with leukoencephalopathy were detected by neuroimaging in all patients. In addition, multifocal microhemorrhages and calcifications were observed by magnetic susceptibility-weighted imaging (SWI) series in 3 patients. Brain biopsy performed on 1 case disclosed a neuronal reduction in the cerebral cortex, loosening of focal white matter, multifocal lymphocyte infiltration, fresh hemorrhages, and gliosis, as well as angiomatous changes of blood vessels with hyalinized thicken-wall, stenotic or occlusive lumina and calcification deposits. The compound heterozygous mutations of n.*10G>A and n.82A>G in SNORD118 were identified in 1 case by target-capture next-generation sequencing. Sanger sequencing verified that the variant n.*10G>A was a novel mutation and it was of paternal-origin, while the variant n.82A>G was of maternal-origin, which had already been reported to be pathogenic to LCC. Follow-up study had shown continued partial seizure in 1 case and remissive claudication in another, while the remaining 2 cases had a relatively favorable outcome without obvious neurological symptoms at present time. Conclusions: The clinical manifestations of LCC are nonspecific, and the onset of the disease tends to be insidious. The triad neuroimaging findings of cerebral calcifications, cysts and leukoencephalopathy are essential to the diagnosis of the disease, and the signals of microhemorrhages revealed by SWI series provide another eloquent reference for the diagnosis. As biopsy is invasive and usually unavailable in the early stage, gene assessment, instead of pathological data, should be the gold standard in the diagnosis of LCC.
Assuntos
Calcinose , Cistos do Sistema Nervoso Central , Leucoencefalopatias , Calcinose/complicações , Calcinose/diagnóstico , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Estudos RetrospectivosRESUMO
Objective: To assess the reading speed of normally-sighted young Chinese with the International Reading Speed Texts (IReST) Chinese version, and evaluate the normal range of the texts, the equivalence of the ten different texts and the potential clinical value. Methods: Evaluation of diagnostic techniques. Participants aged 18 to 35 years old with junior high school or above education and best corrected visual acuity no less than 0.6 were recruited. Best corrected visions of both eyes and binocular vision were tested, and ocular and nervous system diseases were excluded with slit-lamp microscope and funduscope. All the ten texts were read aloud at a distance of 40cm one by one according to a random sequence for each participant. Reading speeds were calculated based on the reading time measured with a stopwatch and number of characters read correctly. The procedure was repeated once again a week later. Data were collected with Epidata and further analyzed with R software. Data accorded with normal distribution and homogeneity of variance were compared by t-test, or by rank sum test. Results: One hundred and three volunteers aged (26.0±2.8) years old participated in the survey. Among them, 66% were female, 96.1% had college education, 53.4% wear glasses in daily life. The best corrected vision of both distance and near were 1.0 (decimal). For the first test, average reading speed for all the participants and texts was (295±51) characters/min,much faster than the normal range provided by the reading cards. No significant difference was found between different texts, and the biggest variance between texts was 11 characters/min(P>0.05). The average reading speed of the second test was (315±53) characters/min, which was faster than the first one (P<0.05) . No statistic relationship was found between reading speed and age, education level or wearing of glasses. However, women read faster than men, and significant difference was found between male and female volunteers in 5 texts during the first test. Conclusions: Normally-sighted young Chinese readers read faster than the normal range provided by IReST cards. There is significant variance of reading speed between different individuals. Although learning effect due to the repeated tests should be considered, the ten texts are of favorable consistency. IReST can be a useful tool for assessing reading performance, especially for comparing results before and after interventions with different texts. (Chin J Ophthalmol, 2018, 54: 120-124).
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Leitura , Testes Visuais , Adolescente , Adulto , Povo Asiático , Feminino , Humanos , Masculino , Valores de Referência , Microscopia com Lâmpada de Fenda , Adulto JovemRESUMO
In this paper we describe a novel ion source named DUHOCAMIS for multiply charged metal ion beams. This ion source is derived from the hot cathode Penning ion gauge ion source (JINR, Dubna, 1957). A notable characteristic is the modified Penning geometry in the form of a hollow sputter electrode, coaxially positioned in a compact bottle-magnetic field along the central magnetic line of force. The interaction of the discharge geometry with the inhomogeneous but symmetrical magnetic field enables this device to be operated as hollow cathode discharge and Penning discharge as well. The main features of the ion source are the very high metal ion efficiency (up to 25%), good operational reproducibility, flexible and efficient operations for low charged as well as highly charged ions, compact setup, and easy maintenance. For light ions, e.g., up to titanium, well-collimated beams in the range of several tens of milliamperes of pulsed ion current (1 ms, 10/s) have been reliably performed in long time runs.