Congenital myasthenic syndrome 22 due to PREPL gene mutation in 2 patients: case report and literature review / 中华实用儿科临床杂志

Clinical data of two patients with congenital myasthenia syndrome type 22 (CMS22) treated at the Children′s Hospital of Fudan University from February 2019 to November 2021 were retrospectively analyzed, and relevant literatures were reviewed.Both patients were female, aged 3 months 18 days and 3 months 26 days, respectively, with typical clinical features of CMS (postnatal onset, skeletal muscle weakness, feeding difficulties, and delayed motor development). Genetic testing revealed that one patient had a homozygous frameshift mutation of the PREPL gene from maternal uniparental disomy c. 1282_1285del(p.F428fs*18), and the other one had a compound heterozygous mutation, including the paternal homozygous frameshift mutation of the PREPL gene and maternal monoallelic nonsense mutation and splicing mutation c. [1501G>T; 2020+ 1G>T], p.[G501*; -]. Two patients were treated with Pyridostigmine bromide at the age of 6 months old and 4 months old, respectively, and the medication last for 15 months and 3 months (still under treatment), respectively.The treatment was effective.Through literature review, 7 English language articles were retrieved, involving 13 cases (2 cases in the presented study were included). The main clinical symptoms of CMS22 included neonatal onset with feeding difficulties and motor development delay, accompanied by cognitive impairment, growth hormone deficiency, and obesity.Genetic testing is favorable to the early diagnosis, early treatment, and symptom relief.

Clinical phenotype and genetic characteristics of patients with typical 16p11.2 microdeletion syndrome / 中华神经科杂志

Objective:To analyze the clinical phenotype, copy number variation, treatment and follow-up characteristics of children with typical 16p11.2 deletion syndrome.Methods:The clinical data of 10 children with typical 16p11.2 deletion syndrome who were treated in the Department of Neurology, Children′s Hospital of Fudan University from August 2011 to December 2021 were retrospectively collected, and their clinical phenotype, copy number variation, treatment and follow-up were summarized.Results:Among the 10 children, 4 are female and 6 are male, all with epilepsy. Nine patients had epilepsy in infancy, and the age of onset was 6.0 (4.0, 8.5) months. Four cases had focal seizures (1 with fever), 4 had generalized tonic-clonic seizures, and 2 had focal seizures with generalized tonic-clonic seizures. Eight cases had cluster seizures (more than 2 to 10 seizures within 24 hours), and 1 case had 1 status epilepticus. Nine children did not show obvious developmental delay at the onset of epilepsy, and 1 child had developmental delay at the onset of epilepsy at 14 months of age. One child had parallel toes at left foot, and 1 had macrocephaly and low limb muscle tone. Genetic testing found that 10 children carried typical 16p11.2 heterozygous deletion, the starting position of the deletion fragment was Chr16:29478119-29675016, the ending position was Chr16:30125670-30206112, and the deletion length was 525-712 kb, all of which were considered pathogenic variants. In the antiepileptic drug treatment, 4 children were treated with oxcarbazepine, 2 with sodium valproate, 2 was switched to oxcarbazepine after levetiracetam was ineffective, 1 with levetiracetam combined with sodium valproate, and 1 with levetiracetam in combination with sodium valproate and ketogenic diet, and all 10 children had no seizures. One patient developed episodic exercise-induced dyskinesia at school age, and the seizures decreased after treatment with oxcarbazepine. Follow-up of 10 children found that 9 children had different degrees of developmental delay (language was significantly affected), 3 cases were combined with autism-like manifestations, and 1 case had poor comprehension, learning difficulties, and repeated grades after entering regular primary schools.Conclusion:The typical 16p11.2 microdeletion syndrome has the deletion of gene fragments in the proximal region of 16p11.2, characterized by drug-responsive cluster seizures with onset in infancy, which may be accompanied by language delay, autism spectrum disorder and nonspecific malformations.

Clinical characteristics and gene analysis of SMC1A gene related disorders / 中华神经科杂志

Objective:To analyze the clinical characteristics and genetic features of SMC1A gene related disorders. Methods:The data of 5 children with SMC1A gene variants were collected from Children′s Hospital of Fudan University from February 2018 to January 2022. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results:Among the 5 patients, 4 are females and 1 is male. Two female cases are siblings. One boy had dysmorphic features, consisting of bilateral ptosis, synophrys, a short nose and upturned nasal tip. He also had patent foramen ovale plus atrial septal defect, unilateral cryptorchidism and microcephaly. Three cases had microcephaly. Two girls had patent foramen ovale, and 2 girls had microcephaly. Four cases had epilepsy, and age at seizure onset ranged from 2 to 52 months. Multiple seizure types were observed, including bilateral tonic clonic seizures in 2 patients, and focal seizures in 3 patients. The seizures in 3 cases were in cluster. All patients had developmental delay, including 1 patient with mild and 4 patients with moderate to severe developmental delay. Three patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 4 patients, including focal discharges in 3 cases and generalized discharges in 1 case. Brain magnetic resonance imaging was normal in 3 patients and showed mild cortical thickening in 1 case. All cases harbored 4 SMC1A gene variants, including 2 missense variants and 2 frameshift variants (c.580_587del, c.2699delG, c.3362G>A, c.1486C>T). Three cases harbored heterozygous SMC1A variants and 2 cases carried somatic mosaic SMC1A variants with 17.5% and 88.1% mosaicism in peripheral blood. The follow-up lasted for 3 months to 4 years. The epilepsy was refractory in 2 cases. During the follow-up, all cases had very slow developmental progress or developmental retardation. All cases had different levels of growth retardation. The scores of Cornelia de Lange syndrome (CdLS) phenotypes in 5 cases were 2-6. One case had the combined phenotypes of atypical CdLS and developmental epileptic encephalopathy (DEE). The phenotype was atypical CdLS in 1 case and DEE in 1 case. The phenotypes of 2 cases with SMC1A missense variants were mild, manifesting as non-refractory epilepsy and moderate to severe developmental delay. Conclusions:All of cases with SMC1A gene variants have developmental delay. Most of the patients have clusters of seizures and some dysmorphisms. The phenotypes of SMC1A gene related disorders are diverse. Except CdLS and DEE, there are some patients with mild phenotype due to missense variants of SMC1A gene.

Clinical diagnosis and treatment of 9 childhood opsoclonus-myoclonus syndrome patients and application of standard rating scale / 中华神经科杂志

Objective:To summarize the clinical features of childhood opsoclonus-myoclonus syndrome (OMS), evaluate severity degree and prognosis using OMS Symptom Severity Standard Rating Scale.Methods:The clinical features,diagnosis, therapeutic regimen and follow-up of 9 children with OMS in Department of Neurology and Oncology Department of Children's Hospital of Fudan University between 2011 and 2019 were retrospectively reviewed. Severity degree and prognosis were evaluated using OMS Symptom Severity Standard Rating Scale.Results:Among the 9 children with OMS, 4 were males and 5 were females. The onset age ranged from 14 months to 5 years, with a median of 17 months. Main symptoms were opsoclonus, myoclonus, ataxia, motor function regression, behavior and mood changes and sleep disorders. Eghit patients were combined with tumor. Seven of them with neuroblastoma were confirmed by surgical pathology, the other one showed spontaneous regression and symptom remission without treatment. Eight patients received hormone combined with intravenous immunoglobulin, of which 3 cases received adrenocorticotropic hormone, while 5 cases received methylprednisolone pulse therapy, with prednisone sequential therapy, decreasing dose gradually. Rituximab was administrated in 3 patients whose annual recurrent time was≥2. Nine patients were divided into 3 groups according to OMS Symptom Severity Standard Rating Scale, 1 of mild degree, 3 of moderate degree, 5 of severe degree. There was no recurrence and sequelae in the mild-degree patient after 3 years follow-up. There was no recurrence and sequelae in 2 of the moderate-degree patients after 1-2 years follow-up. Different degrees of motor, cognitive sequelae were found in 1 of moderate-degree patients and all of severe-degree patients after 1-8 years follow-up.Conclusions:Childhood OMS patients have early onset age. Bad symptom severity before treatment and multiphase course are associated with poor prognosis. OMS Symptom Severity Standard Rating Scale is suitable for estimations of long-term prognosis.

Clinical features and genetic analysis of the early-onset epileptic encephalopathy caused by sodium channel mutations / 中华实用儿科临床杂志

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.

Two cases of Christianson syndrome caused by SLC9A6 gene mutation / 中华神经科杂志

Christianson syndrome is a rare X-linked disease caused by mutations in the SLC9A6 gene. The clinical manifestations are male developmental delay, language disorder, seizures, mental retardation, ataxia, microcephaly and so on. Two cases of male children with Christianson syndrome were reported. The proband was 1 year and 11 months old. Clinical manifestations include microcephaly, global developmental delay, and seizures. The electroencephalogram showed that the central midline region of spikes and slow waves were emitted, and all exons sequencing detected a mutation in the SLC9A6 gene chrX: 135084373 [c.803+1(IVS6)G>A]. The proband′s brother was 4 years and 8 months old. The clinical manifestations were similar. The electroencephalogram showed spikes and spines in the Rolandic area on both sides. Slow waves and spiny slow waves were emitted. Magnetic resonance imaging suggested brain atrophy. The genetic verification results were consistent with the proband. The SLC9A6 gene c.803+1(IVS6) G>A splicing mutation was a pathogenic mutation in this family.

Clinical analysis of nine infants with tyrosine hydroxylase deficiency / 中华神经科杂志

Objective:To explore the clinical characteristics of children with tyrosine hydroxylase deficiency (THD) in order to recognize this disease early as to optimize the treatment to improve the prognosis.Methods:A retrospective analysis was done on the clinical data of nine children with THD who were diagnosed at the Children′s Hospital of Fudan University from May 2018 to May 2020, including name, gender, age, age of onset, age of presentation, age of diagnosis, clinical manifestations, head imaging, tyrosine hydroxylase gene mutation, treatment, follow-up, and other results, which were classified according to Willemsen′s method, and the clinical characteristics were summarized and a literature review was carried out.Results:There were five males and four females with the age at onset ranged from newborn to two years and six months (median three months). The duration of diagnosis ranged from four months to five years and seven months (median nine months). The presenting symptom was motor retardation in seven cases. Clinical symptoms included hypokinesia in eight cases, limb dystonia in five cases, truncal hypotonia in four cases, dysphagia/dysarthria in four cases, oculogyric crises in four cases, tremor in three cases, rigidity in three cases, mask faces in three cases, bilateral ptosis in two cases, hypersalivation/sweating in two cases, diurnal fluctuation in two cases, myoclonic jerks in one case, and status dystonicus in one case. Cranial magnetic resonance imaging was normal in seven cases and non-specific in two cases (backward myelination in one case and bilateral ventricle enlargement and decreased white matter in another one). Eight tyrosine hydroxylase gene variants were found, including four missense variants, two frameshift variants, one shear variants and one nonsense variant, as well as three novel variants [c.1505_1518dup (p.R507Afs *23), c.1128_1138del (p.Q377Gfs *12), c.1058A>G(p.H353R)]. All patients were treated with levodopa and benserazide hydrochloride tables. The initial and maintenance doses of type A were 1.7-8.3 mg·kg -1·d -1 and 4.5-20.0 mg·kg -1·d -1, respectively. The initial and maintenance doses of type B were 1.7-12.5 mg·kg -1·d -1 and 4.6-12.0 mg·kg -1·d -1, respectively. In type A, four patients had dyskinesis which was relieved by decreasing the dose or maintaining the same dose of levodopa. One case of type B had dyskinesis which was self-resolving. Conclusions:Although the clinical manifestations of this disease are varied, the initial symptoms in children with onset within the first year of life are mostly hypokinesia, truncal hypotonia, and dystonia in limbs. It is recommended that children with THD, regardless of clinical type, should start at the minimum dose for easy segmentation in the range of 1.0-5.0 mg·kg -1·d -1, and the maintenance dose can be adjusted according to the individual response of the child. The incidence of dyskinesia of this disease is not low, but most can be treated by decreasing the initial dose and delaying the dosage rate.

A phenotypic and genetic study on β-propeller protein-associated neurodegeneration / 中华儿科杂志

Objective@#To summarize the clinical and genetic features of β-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.

Novel compound heterozygous TBC1D24 mutations in a boy with infantile focal myoclonic epilepsy and literature review / 中华儿科杂志

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.

Analysis of gene mutation of early onset epileptic spasm with unknown reason / 中华儿科杂志

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.

Application of ICF-CY in Family Rehabilitation of Children with Duchenne Muscular Dystrophy / 中国康复理论与实践

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.

Clinical characteristics and genetic researches of CHD2 myoclonus encephalopathy / 中华实用儿科临床杂志

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.

Use of the ketogenic diet as treatment for refractory epilepsy and autism in the paediatric age / 中华实用儿科临床杂志

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.

Clinical features and efficacy of different treatments on 5 cases with Landau-Kleffner syndrome with poor prognosis / 中华实用儿科临床杂志

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.

Clinical analysis of twelve cases with cerebral venous sinus thrombosis in children / 中华神经科杂志

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.

Polymorphism of multidrug-resistance gene in childhood refractory epilepsy / 临床儿科杂志

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.

Exploration for pathogenic factors and diagnosis of cerebral palsy in children / 临床儿科杂志

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.