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Objective:To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS + ) caused by the KCNT2 gene mutation and review the literature. Methods:Clinical data of a child with GEFS + and his family members who visited Department of Pediatric Neurology, Guangzhou Women and Children′s Medical Center in May 2019 were collected.DNA samples were collected from the peripheral blood of the proband, his parents, his elder brother, and his maternal grandparents, and genetic analysis and verification were performed using the next-generation sequencing technique.Using " KCNT2" as the key word, literature was retrieved from PubMed, China National Knowledge Infrastructure and Wanfang databases (up to August 2019). Results:The proband was a 3-year-old boy who was admitted to Guangzhou Women and Children′s Medical Center because of frequent epileptic seizures in the past 5 months.He presented with a binocular gaze and experienced 3 to 8 times of extremities myoclonic-spastic epileptic attacks every day.He had a history of 3 times of febrile seizures at the age of 2 years old.His seizures were refractory to Sodium valproate, Topiramate, Nitrazepam and Levetiracetam.His elder brother and mother had a history of childhood febrile seizures.Other members in the family had no history of convulsion.Ictal electroencephalogram showed general 1 Hz high voltage spike-slow waves.A heterozygous nonsense mutation of KCNT2 gene c. 574C>T(p.Q192X) that was never reported previously was detected in the proband, his brother, mother and maternal grandmother.Furthermore, no other family members carried the mutation at the c. 574 locus of the KCNT2 gene.No article in Chinese was found, and 2 articles in a language other than Chinese provided the complete data of 3 sporadic cases.Together with 4 cases in the family studied in this article, there were 7 cases and 4 mutation sites in KCNT2 gene.Of these mutations, there were 3 missense mutations and 1 nonsense mutation.Three sporadic patients presented with early infantile epileptic encephalopathy.The family of this study was characterized with febrile seizures and febrile seizures plus. Conclusions:A de novo mutation and phenotype of the KCNT2 gene is found in a family with GEFS + .It would expand the gene mutation spectrum and provide basis for family genetic counseling. KCNT2 mutation induced GEFS + is refractory to antiepileptic drugs.
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OBJECTIVE@#To provide a basis for genetic counseling and clinical precision therapy by exploring the genetic etiology of a child with recurrent hypoglycemia convulsion accompanied by language retardation.@*METHODS@#Peripheral blood samples were obtained from the proband, his sister and his parents. Whole genomic DNA was extracted and analyzed by the whole exon gene sequencing and confirmed by Sanger sequencing.@*RESULTS@#The proband and his sister were found to carry compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene, which had not been reported in the past, the c.731T>A (p.M244L) site was derived from the maternal heterozygous mutation, while c.928G>A (p.G244S) site from the father heterozygous mutation.@*CONCLUSION@#The compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene were the genetic cause of glycogen storage syndrome type 0 in children, providing basis for family genetic counseling. When the patient had Hypoglycemia often accompanied with convulsions, which was easy to be misdiagnosed as seizures, and the antiepileptic treatment was ineffective. After genetic diagnosis, the seizure can be controlled by improving diet to maintain blood glucose stability.
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Child , Humans , Exons , Glycogen , Heterozygote , Mutation , Pedigree , SiblingsABSTRACT
Objective To investigate the clinical characteristics,treatment and prognosis of relapsed demyelinating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China.Methods Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children's Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively.Results Ten children were included with the age of (6.4 ± 3.6) years old,and male to female ratio was 4 ∶ 6.(1)Clinical phenotype:all children had 24 episodes during follow-up,with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes,ADEM (9/14 times) was the most common,followed by optic neuritis(ON) (3/14 times) and brainstem encephalitis (2/14 times).By the final follow-up,the final diagnosis was multiphasic disseminated encephalomyelitis (MDEM) (6/10 cases),NMOSD (3/10 cases),ADEM-ON (1/10 case),respectively.(2) Laboratory examination:all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1 ∶ 640) (6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group (1 ∶ 320) (4 cases).(3)Imaging changes:25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage,MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis:intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases),mycophenolate mofetil (4/10 cases),IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD,3 cases of MDEM and 1 case of ADEM-ON,including motor dysfunction,learning disability and inattention,symptomatic epilepsy and visual impairment.Conclusions ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients,residual neurological sequelae were related to the type of repeated demyelination.
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Objective@#To investigate the clinical characteristics, treatment and prognosis of relapsed demyeli-nating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China.@*Methods@#Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children′s Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively.@*Results@#Ten children were included with the age of (6.4±3.6) years old, and male to female ratio was 4∶6.(1)Clinical phenotype: all children had 24 episodes during follow-up, with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes, ADEM (9/14 times) was the most common, followed by optic neuritis(ON)(3/14 times)and brainstem encephalitis (2/14 times). By the final follow-up, the final diagnosis was multiphasic disseminated encephalomyelitis(MDEM)(6/10 cases), NMOSD(3/10 cases), ADEM-ON(1/10 case), respectively.(2)Laboratory examination: all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1∶640)(6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group(1∶320)(4 cases). (3)Imaging changes: 25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage, MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis: intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases), mycophenolate mofetil (4/10 cases), IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD, 3 cases of MDEM and 1 case of ADEM-ON, including motor dysfunction, learning disability and inattention, symptomatic epilepsy and visual impairment.@*Conclusions@#ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients, residual neurological sequelae were related to the type of repeated demyelination.
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Objective To analyze the clinical characteristics of epileptic children at early stage,and to explore the high risk factors for children′s refractory epilepsy(RE)in order to provide evidence for the early and timely treatment of RE.Methods A total of 147 epileptic patients with correct diagnosis and reasonable treatment were enrolled.Forty-nine patients were classified as drug non-responsive epilepsy(DNR-EP group).The remaining 98 patients were classified as drug-responsive epilepsy(DR-EP group).With multiple conditional Logistic regression,the clinical characte-ristics between the 2 groups were compared to identify the early predictors for RE.Results Single factor Logistic regression analysis showed that the initial age of onset <1 year,more than 20 seizures before treatment in a week,focal seizures,more than 2 kinds of epileptic seizures,changes in seizure type in the course of disease,neurological impairment,early intellectual disability,abnormal cranial magnetic resonance imaging(MRI),fixed focal abnormalities on video electroencephalogram(VEEG) after seizure-free interval,diffused anomaly of non-epileptic wave in VEEG before treatment,poor response to initial antiepileptic drugs(AEDs) therapy,compliance with the characteristics of epileptic encephalopathy at early stage significantly increased in DNR-EP group.Then multivariate conditional Logistic regression analysis demonstrated that more than 20 seizures before treatment in a week(OR=2.679,P=0.043),more than 2 kinds of epileptic seizures(OR=4.364,P=0.013),fixed focal abnormalities on VEEG after seizure-free interval(OR=3.898,P=0.008),poor response to initial AEDs therapy(OR=2.611,P=0.036),and compliance with the characteristics of epileptic encephalopathy at early stage(OR=6.022,P=0.002) were the risk factors for developing into RE.Conclusions Children are likely to develop into RE if they have more than 20 seizures before treatment in a week,with more than 2 kinds of epileptic seizures,fixed focal abnormalities on VEEG after seizure-free intervals,poor response to initial AEDs therapy,and compliance with the characteristics of epileptic encephalopathy at early stage.
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Objective To evaluate the correlations between the cerebral hemodynamic changes of severe acute encephalopathy with the clinical features from emergency periods to stable periods and the value of transcranial Doppler ultrasonography( TCD)in cerebral function assess. Methods Thirty patients with acute brain diseases by assisted mechanical ventilator from Jun 2014 to May 2015 in PICU were included and followed up to Nov 2015,then grouped by Glasgow Coma Scale( GCS),MRI,prognosis( mental sequelae after half a year). Each subject was examined through the temporal bone window by TCD at emergency peri-ods and stable periods. The systolic cerebral blood flow velocity( sCBFV),and pulsatility index( PI)of bilat-eral middle cerebral artery( MCA),anterior cerebral artery,posterior cerebral artery were analyzed. Multivari-ant analysis of variance,repeated measures analysis of variance was conducted to compare sCBFV and PI of MCA among groups in different clinical periods. The variants included sex,disease diagnosis,prognosis, MRI,GCS,and the first abnormal TCD. The variation within groups was tested via a Hotelling T2 test. All sCBFV and PI of each artery and the D-value of sCBFV between the different periods were compared accord-ing to the prognosis groups. Results (1)Five patients could be lateralized,and their lateralization of MRI focus was consistent with the abnormal sides of sCBFV in the stable periods.(2)The D-value of sCBFV in left MCA between the different periods in the poor prognosis group was significantly higher than that in the good prognosis group[(71. 93 ± 58. 21)cm/s vs.(33. 20 ± 30. 23)cm/s,t = -2. 287,P =0. 033].(3) Multivariant analysis of variance showed that GCS classification and disease diagnosis were significantly cor-related with the cerebral hemodynamic changes respectively(P =0. 042,0. 005,respectively).(4)sCBFV and PI of left MCA reduced significantly in the stable periods than those in the emergency periods( P =0. 002,0. 003,respectivly). Conclusion The cerebral hemodynamic changes by TCD from emergency peri-ods to stable periods are consistent with the clinical status,dynamic evaluation by TCD may facilitate the evaluation of brain dysfunction in the severe acute encephalopathy.
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@#Objective To observe the effects of electro-acupuncture and functional training on gross motor function of children with cerebral palsy. Methods 137 children with cerebral palsy were divided into observation group (n=81) and control group (n=56). The observation group received electro-acupuncture and functional training, and the control group received functional training only. Results The scores of Gross Motor Function Measure (GMFM) increased in both group after treatment (P<0.01), and it was significantly higher in the observation group than in the control group (P<0.01). Conclusion Electro-acupuncture and functional training is superior to functional training in gross motor function.
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Objective To investigate the clinical manifestation of convulsive status epilepticus (CSE) associated with the outcome of children contracted this illness in order to make an effort to prevent and treat those children. Method The patients with CSE admitted from October 1998 to October 2008 were prospectively and consecutively enrolled. All the patients met the diagnostic criteria set by International Anti-epilepsy Union (ILAE) in 1993. The prognosis predictors of outcome were analyzed with the Rank sum test, Chi-square analysis and Logistic regression analysis. Results A total of 169 patients with CSE were enrolled. Of them, 92 patients were from rural areas (54.4% ). The primary cause was central nervous system infection, and the minor ones were a reduction of dose or withdrawal of the antiepileptics, and cerebral hemorrhage. The duration of CSE before treatment was longer in rural patients than in urban residents ( P < 0.01) . The duration of CSE before treatment and the total persistence time of CSE was significantly associated with the mortality 14.2% . The source of patients, the duration before treatment, and respiratory depression were independent prognostic predictor variables of CSE (P < 0.05) .Conclusions The rural patients account for the major ratio of convulsive status epilepticus. Central nervous system infection is the primary cause. The duration before treatment and total persistence time of CSE are highly related to the mortality and morbidity.