Factors influencing neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy: a follow-up study of 21 cases / 中华实用儿科临床杂志

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.

Analysis of a family with inherited generalized epilepsy with febrile seizures plus caused by the KCNT2 mutation and literature review / 中华实用儿科临床杂志

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.

Study on the cerebral hemodynamic changes by transcranial Doppler ultrasonography from emergency ;periods to stable periods in severe acute encephalopathy children / 中国小儿急救医学

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.

The factors influencing the prognosis of herpes simplex virus encephalitis / 中华实用儿科临床杂志

Objective To evaluate the factors influencing prognosis and to explore the pathological mechanism in which herpes simplex virus encephalitis(HSE) was one of the severe types of acute viral encephalitis in children and had poor prognosis.Methods Twenty-one children with HSE were diagnosed by the clinical syndrome of focal encephalitis and HSV DNA-PCR positive in cerebrospinal fluid(CSF) from Jan.2012 to Oct.2013,among whom,19 patients were treated with intravenous Acyclovir,30 mg/(kg · d) 48 hours after onset and were followed up for 6 to 24 months.Clinical data were collected including Glasgow Coma Score,the brain magnetic resonance imaging(MRI),and electroencephalography(EEG).All MRI examinations including plain scan and contrast enhancement were carried out at the beginning of admission and 1 month after the onset of symptoms.The clinical outcomes were divided into two levels accoming to the severity of the neurological deficit,then the data were analyzed by using Logistic regression and Fisher's exact probability method.The OR value was calculated.Results Eighteen children survived,of whom 5 cases had no neurological deficit(27.8％),3 cases were left with mild impairment(16.7％),and the above 8 cases were thought to have better outcome.Six cases had moderate impairment (33.3％) and 4 cases had severe impairment(22.2％) and 1 child died,and these 11 cases were thought to have worse outcome.Patients aged between 1 month and 10 years,average (2.03 ± 2.23) years old.The mean GCS score was (9.68 ± 2.65) scores,the GCS of the patients were more than 7except for one death child with 3 scores.The multiple factor analysis showed that EEG,age,GCS and the range and character in MRI were significantly correlative to the prognosis(P ＜ 0.05).The single factor analysis illustrated that age 1-4 years old(OR =30,95％ CI 2.066-366.510,P =0.002),GCS ≤ 10 scores(OR =27.518,95％ C1 2.066-366.510,P =0.004)and the wide necrosis existence involving diffuse white matter or deep nuclei of MRI findings (OR =12,95 ％ CI 1.294-111.323,P =0.017) indicated the worse outcome.Conclusions Age,GCS score,nature and damage degree of MRI lesions are the main important factors affecting the prognosis of children's HSE.HSE in children is apt to involve the cortex such as frontal lobe,parietal lobe even diffuse white matter or deep nuclei,which indicates the poor prognosis.

Recent memory consequences of drug-resistant medial temporal lobe epilepsy and MRI-positive hippocampns / 中华神经科杂志

Objective To assess the effects of MRI-positive and interictal epileptic charges(IEDs) dominance on the memory of the patients with drug-resistant medial temporal lobe epilepsy (MTLE). Methods Fifty right-handed patients(age ranging from 16 to 60 years old)diagnosed as drug-resistant MTLE in our hospital with normal intelligence between September 2006 and April 2007 were investigated. All patients were classified as left MRI-positive(MRI(+)),right MRI(+),MRI(-),bilateral MR[ (+)by high-quality MR[protocol.The EEG was defined as dominant IEDs if≥75%independent IEDs was confined to one temporal lobe in all EEG recordings.Clinical memory scale was administered as memory assessment of MTLE.ANOVA and non-parametric statistics were used to analyze the data in SPSS 12.0. Results The distribution of age,sex,education,occupation,living condition,course,seizure and treat among left MRI(+),right MRI(+),MRI(-),bilateral MRI(+)groups was similar.All scores in the patients with MTLE was significantly lower than normal(P＜0.05).Right MRI(+)MTLE patients had deftcits in nonsense graphics recognition(9.42±7.46)compared to left MRI(+)and MRI(-) groups((16.26±4.43)and(18.26±5.49),F=4.281,P＜0.05).Among MRI(-)patients,left IEDs,right IEDs and bilateral IEDs groups displayed not significantly different impairment in memory. Conclusion Right MRI(+)MTLE has more severe impairment in non-verbal memory,and nonsense graphics recognition can be used to detect the deficit.

A group of children with special benign partial epilepsy:study of clinical features and pathophysiology / 中华神经科杂志

Objective To investigate clinical features and the pathophysiology of 43 children with atypical idiopathic partial epilepsies of childhood(IPEC)that is unclassified according to the International League Against Epilepsy classification.Methods All the children with partial epilepsy of childhood in out hospital were followed up,including those age-related cases with benign process and excluding those with benign epilepsy of childhood with centro-temporal EEG foci,Panayiotopoulos type and Gastaut type.We reviewed their EEGs,seizures and therapeutic data to analyze the semiologieal characters and the interietal activities during they were awake and sleeping.Results The average age of onset of epilepsy was 8.84years old.Frontal absences(43.2%),adversive seizures(47.7%)were more common.Everyday seizures occurred in 38.6%of patients and monthly seizures in 56.8%of patients.Atypical focal(43.2%),multifocal(27.3%),and generalized spike and waves(29.5%),were more predominant in frontal location when they were awake.During sleep,sharp waves generalized or the amplitude increased.At the last follow-up,88.6%of patients were in complete clinical remission and EEG in 22.7%of cases was normal.Among them 2 patients had stopped taking antiepileptic drugs(AEDs)and 6 patients were reducing the doses of AEDs.EEG Was abnormal only in sleep or decreased synchronization.The patients were more responsive to earbamazepine combined with sodium valproate(P<0.01).Conclusion Special partial epileptic syndrome is age-related,having excellent prognosis,which might origin from the frontal lobe.

The syndromic classification of the International League Against Epilepsy (1989): a clinical application study / 中华神经科杂志

Objective To determine the distribution of various epilepsies and epileptic syndromes in the epileptic population treated in epilepsy clinics. Methods Totally 1191 patients with seizures visited between April and September, 2004 in epilepsy center of our hospital were analyzed based on International League Against Epilepsy (1989, ILAE) Classification. Results Of the 1191 cases, partial epilepsies and syndromes were 766 cases (64.3%), generalized epilepsies and syndromes were 240 cases (20.2%), epilepsies and syndromes undetermined whether partial or generalized were 79 cases (6.7%), special syndromes were 16 cases(1.3%),other non-epileptic disorders were 90 cases (7.6%). Symptomatic cases were dominant in partial epilepsies and syndromes, and idiopathic cases were dominant in generalized epilepsies and syndromes. Conclusions Most of epileptic patients might be classified accurately. Treatment should be administered as earlier as possible. The distribution of various epilepsies and epileptic syndromes is regular.