Objective To analyze the clinical features and efficacy of different treatments on 5 cases with Landau-Kleffner syndrome (LKS) with poor prognosis.Methods Five patients with LKS who had poor prognosis were enrolled in the Children's Hospital of Fudan University from September of 2008 to December of 2012.The clinical features and findings of video electroencephalograph (VEEG) of these patients were analyzed.In addition,the outcomes of treatments (antiepileptic drug,corticosteroids and ketogenic diet) on LKS who had poor prognosis were studied.The outcome of epilepsy was classified by using the Engel classification scheme and the outcome of electrical status epilepticus during sleep (ESES) was classified by the decrease in spike wave index (SWI).Results All of 5 patients (2 male and 3 female) had auditory agnosia and epileptic seizure.All patients had normal background activity and epileptiform discharges,and the location of epileptiform discharge was mainly from bilateral temporal;3 patients had ESES.Four out of the 5 patients had refractory epilepsy and the other one got seizure free with antiepileptic drug.Four patients received corticosteroids for 6 months.The aphasia disappeared in 1 patient,improved in 1 patient and sustained in the other 2 patients.Three patients who had ESES did not response to corticosteroids.Among 3 patients receiving ketogenic diet,1 patient was seizure free and the ESES disappeared;in another SWI was reduced;the rest one had a significant reduction in seizure.All the patients had improvement in their aphasia and cognition,however they still had cognitive disorder of various degrees.Conclusions The patients who had multiple seizure type or special seizure type may have poor outcome.Most of these patients have refractory epilepsy or persistent ESES.Corticosteroids can improve aphasia and cognition,but the persistence of ESES can make aphasia and cognition worse.Ketogenic diet can be used as an alternative treatment for refractory epilepsy or persistent ESES in LKS.

In recent years,with the improvement of the genetic inspection techniques,some of the epileptic en-cephalopathy whose causes were unknown are associated with genetic factor.The result shows that one kind of epileptic encephalopathy may be associated with a variety of genetic mutations or copy number variation (CNV),one gene muta-tion or CNV also may lead to a lot of epileptic encephalopathy.In addition,the new clinical features and genetic poly-morphism were discovered increased.So that epileptic encephalopathy which named from the disease -causing gene was also increased.This article will summarize the clinical phenotype characteristics,genetic studies and future of the newly discovered CHD2 myoclonus encephalopathy.

There has been great progress in seizure control with the development of antiepileptic drugs,but 30％ of epileptic children are refractory to antiepileptic drugs.In order to control intractable epilepsy and improve neurodevelopment prognosis,the non-drug therapy such as surgery,vagus nerve stimulation and ketogenic diet (KD) can be taken.Despite its indisputable effectiveness,the functioning of the KD has not been explained.Now the antiepileptic mechanism and neuroprotective mechanisms are studied mainly.It is reported that KD is effective in variety of refractory epilepsy,and recent studies have shown that KD promising in the treatment of children with autism.Although KD is effective,it is worth further study that including its mechanism,recipe,clinical application,and so on.

To explore the pathogenic factors and diagnosi s of cerebral palsy (CP) in children, perinatal history, clinical evaluation, im aging and electrophysiological data and parents' attitude for rehabilitation of CP were analyzed and investigated in 50 children with CP retrospectively. The re sults showed that prem ature birth, low birth weight and perinatal asphyxia were the most pathogenic fa ctors induced CP. The common CP types was spastic paralysis, in particular quadr iparesis. Abnormal CT and MRI findings were detected in 68% of CP children. It w as noticed that 44% of CP children were with speech and language disorder, 32% w i th mental retardation, 18% with hearing impairment, 16% with visual impairment a nd 16% with epilepsy. There were 86% parents to accept with physiotherapy on the ir CP children, 68% with acupuncture therapy, 46% with occupational therapy and 100% with speech therapy, respectively. It is suggested that multi-subjec t cooperation will be necessary for the follow-up study of the high- risk infants. The realization of the related-speciality knowledge a nd the enhancement of rehabilitational conception will be helpful for the early diagnosis and intervention of CP patients. The popularization of rehabilitationa l conception will be also important in the parents with CP children.

Objective To summarize the etiological,clinical and imaging characteristics of cerebral venous sinus thrombosis (CVST) in children so as to provide the basis for early diagnosis and prompt treatment.Methods All the medical records including clinical manifestations,laboratory data,neuroimaging changes,treatment and short-term prognosis were analyzed retrospectively in 12 cases of CVST hospitalized in Children' s Hospital of Fudan University from Aug 2008 to May 2012.Results (1) Regarding the etiology:of the 12 cases,the causes of CVST were infection (2/12),intracranial tumor (1/12),nephrotic syndrome (2/12),cryptogenic disease (7/12).Seven out of all 12 cases without definite cause were presented subacute or chronic headache associated with progressive or acute exacerbation.Seven cases had been misdiagnosed.(2)Diagnosis:All 12 cases were made a definite diagnosis as CVST after neuroimaging examination of brain magnetic resonance imaging combined with magnetic angiography venography.(3) Short-term prognosis:all the patients were treated with anticoagulation,and 11 cases improved.Four of 7 cases with cryptogenic disease had different degrees of visual impairment,and no improvement were found after the treatment; One patient died although accepted digital subtraction angiography and balloon catheter technique.Conclusions Cerebral venous sinus thrombosis has no specific clinical manifestations and a high rate of misdiagnosis.Increased consideration and prompt magnetic angiography venography play a key role in the accurate diagnosis.Anticoagulation is safe and effective.

Objective To discuss the diagnosis of refractory epilepsy (RE) in children, and to study the association of the single nucleotide polymorphisms (SNPs) of muhidrug-resistance gene (MDR1) C3435T with pharmaco- resistant epilepsy. Methods Four hundred children with epilepsy were retrospectively or prospectively identified from multiple sources in our hospital in Shanghai and were followed-up for the occurrence of refractory epilepsy. The clinical features of RE regarding age at onset, gender, seizure type, electroencephalogram, neuroimaging, development of central nervous system, etiology and prognosis etcetera were investigated. DNA samples were obtained from 132 patients with epilepsy (70 RE and 62 responsive epilepsy) and 62 health children by DNA extraction kit. Genotype of the C3435T polymorphism was determined by DNA sequence analysis after traditional polymerase chain reaction. The frequency of genotypes and alleles among the three groups was compared by Chi-square test. Results Eighty-three (20.8%) out of total 400 patients were RE. Among them 65 (78.3%) patients failed at least 2 drugs in six months. Forty-two (50.6%) were administered at least 3 drugs on the last follow-up. Medical treatment showed remarkable effective in 6 (7.2%) RE patients, effective in 40 RE patients (48.2%). No effectiveness was seen in another 37 (44.6%) RE patients, however 25 out of 37 presented symptomatic alleviation. Significant difference in genotype (CC, CT, Tr) frequency was neither found between RE and responsive epilepsy patients nor between RE patients and healthy controls. No association between the C3435T polymorphism in the human MDR1 gene and refractory epilepsy was found by logistic analysis. Conclusions Refractory epilepsy could be diagnosed in 6 months after being treated with anti-epilepsy drugs (AEDs) in children with average attack once per month at least and failed more than 2 AEDs. Multiple AEDs were necessary for treatment. No association between the C3435T polymorphism in the human MDR1 gene and refractory epilepsy was found by logistic analysis in this study.

Objective To observation dynamic changes and gender difference of heart rate variability and blood pressure variability in unbonded spontaneously hypertensive rats using Telemetry technology .Method Taking sixteen spontaneously hypertensive rats of 3-month-old in SPF grade, there were implanted TL11M2-C50-PXT device intraperitoneally.Seven days later, respectively monitoring chainless blood pressure and electrocardiogram for 24 h continuously time using telemetry system when 3, 5, 7 months of age in spontaneously hypertensive rats .Analysing 24 h systolic pressure , mean blood pressure , diastolic blood pressure , heart rate variability and blood pressure variability . Result Systolic pressure , diastolic pressure and mean pressure , blood pressure variability increased with age of the moon increased in spontaneously hypertensive rats , moreover female SHR rats of blood pressure variability was significantly lower than that of the male rats .Correlated indexes of heart rate variability had no obvious change Between three to seven month -old in male spontaneously hypertensive rats .But RR interval , SDNN, TP, VLF and HF increased significantly with age of the moon increased in female spontaneously hypertensive rats , moreover the female SHR rats of TP , VLF and HF index of heart rate variability were lower than the male rats .Conclusion With the SHR rats age and blood pressure , blood pressure variability increased , and the female SHR rat variability in blood pressure and heart rate was significantly lower than that of the male .

Objective To explore the feasibility of assessments of functional and environmental factors in children with Duchenne mus-cular dystrophy (DMD) under the frame of International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY). To execute family intervention and to evaluate its effects. Methods A 6-year-and-5-month-old boy with DMD was enrolled to the study. Functional and environmental factors were assessed with the North Star Ambulatory Assessment (NSAA), time tests, hand-held dyna-mometry assessment, body mass index and family interview. Plans of family intervention were settled and executed for one year and at the end of intervention, the boy received all the above assessments to compare the effects of intervention. Results After one-year family inter-vention, the muscle strength was improved or maintained in most muscles except abductors of hip and the body mass index did not change. For the activities, the scores of NSAA increased and maintained, and the result of time tests improved. Otherwise, attitude and execution of parents were improved. Conclusion It is feasible to execute family intervention under the frame of ICF-CY in children with DMD. Both children and their family may benefit from the intervention.

OBJECTIVE: To explore the clinical features and genetic variant in a child with Cerebral creatine deficiency syndrome (CCDS). METHODS: A child who had presented at the Affiliated Children's Hospital of Fudan University on March 5, 2021 was selected as the study subject. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing. The level of creatine in the brain was determined by magnetic resonance spectroscopy. RESULTS: The patient, a 1-year-and-10-month male, had presented with developmental delay and epilepsy. Both his mother and grandmother had a history of convulsions. MRS showed reduced cerebral creatine in bilateral basal ganglia and thalamus. The child was found to harbor a hemizygous splicing variant of the SLC6A8 gene, namely c.1767+1_1767+2insA, which may lead to protein truncation. The variant was not found in the public databases. Both his mother and grandmother were heterozygous carriers for the same variant. CONCLUSION The hemizygous c.1767+1_1767+2insA variant of the SLC6A8 gene probably underlay the CCDS in this child. Discovery of the novel variant has also expanded the mutational spectrum of the SLC6A8 gene.
Humans ; Male ; Amino Acid Metabolism, Inborn Errors ; Brain ; Creatine/genetics* ; Heterozygote ; Mothers ; Nerve Tissue Proteins ; Plasma Membrane Neurotransmitter Transport Proteins/genetics* ; Infant

Objective:To explore the clinical phenotype characteristics of early-onset epileptic encephalopathy (EOEE) caused by sodium channel mutations.Methods:A retrospective study was used.A total of 52 EOEE patients treated in the Department of Neurology, Children′s Hospital of Fudan University and Department of Neurology, Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from June 2016 to June 2019 were recruited.Peripheral blood samples of 52 patients and their parents were collected for analyzing pathogenic mutations by the next generation sequencing and copy number variations of whole exons in family. Chi- square test was used to compare seizure control data among different voltage-gated sodium channel α1 subunit ( SCN1A) mutation types. Results:A total of 35/52 cases (67.3%) were diagnosed as Dravet syndrome, 3/52 cases (5.8%) were West syndrome, and 14/52 cases (26.9%) were non-symptomatic EOEE.The electroencephalogram (EEG) findings showed a large number of multifocal spikes, spike-slow waves, sharp waves, and sharp-slow waves.A total of 45/52 cases (86.5%) showed normal brain magnetic resonance imaging(MRI), 1 case had slightly widened bilateral frontal sulcus, 1 case had widened bilateral temporal pole and frontal top subarachnoid space, and the remaining 5 cases had widened extracerebral space and slightly larger ventricles.Thirteen cases were re-examined with brain MRI, and 3 cases had mild brain atrophy.A total of 43/52 cases (82.7%) were examined with SCN1A gene mutations, of which 28/52 cases (53.8%) were missense mutations, 5/52 cases (9.6%) were nonsense mutations, 7/52 cases (13.5%) were frameshift mutations and 3/52 cases (5.8%) were splice site mutations.A total of 3/52 cases (5.8%) had SCN2A mutations, of which 2/52 cases (3.8%) were missense mutations, and 1/52 case (1.9%) was a frameshift mutation, 1/52 cases (1.9%) carrying the missense mutation of the SCN3A gene.A total of 5/52 cases (9.6%) had missense mutations of the SCN8A gene.After an average of 1-year follow-up, a total of 13/52 cases (25.0%) had more than 1-year control of seizure, of which 6/52 cases (11.5%) with seizure control for more than 2 years, and 4/52 cases (7.7%) with more than 3-year control.Children carrying SCN1A missense mutations were relatively easier to be controlled for seizures than those carrying SCN1A truncation mutations (nonsense mutations+ frameshift mutations) ( P<0.05). In 5 children carrying SCN8A mutations, 2 cases of them had seizures control for more than 1 year after adding Oxcarbazepine, but the improvement of mental motor function was not obvious. Conclusions:In children with EOEE associated with sodium channel gene mutations, SCN1A, SCN2A, SCN3A, and SCN8A mutations were pathogenic factors.Among them, SCN1A was the most common pathogenic gene for EOEE, with the mutation rate of 82.7%.Dravet syndrome was the most common clinical phenotype of EOEE associated with sodium channel gene mutations.Epileptic seizures in children carrying SCN1A missense mutations were easier to be controlled than those with truncated mutation (nonsense mutations + frameshift mutations), suggesting that the gene mutation type was related to the degree of seizures control.Oxcarbazepine was effective in the treatment of EOEE with SCN8A gene mutations, indicating that the combination therapy using anti-epilepsy drugs can be applied to EOEE patients according to the type of gene function.