Progress on adverse reactions and prevention and treatment of ketogenic diet therapy / 国际儿科学杂志

Ketogenic diet(KD)is a formulation diet with a high proportion of fat, low proportion of carbohydrates, appropriate protein and other nutrients, which has been used for centuries in the treatment of refractory epilepsy.In recent years, KD has been shown to be effective in the treatment of other diseases, such as amyotrophic lateral sclerosis, traumatic brain injury, diabetes, obesity, etc.Although KD has a positive effect on the treatment of a variety of diseases, the short-term and long-term adverse reactions caused by the imbalance of its nutritional structure should not be ignored.This article reviews the adverse reactions of KD in the treatment of children with refractory epilepsy and the corresponding prevention and treatment measures, to guide safe and efficient implementation of KD therapy in the clinic.

A case report of Joubert syndrome caused by KIAA0586 gene mutation / 中华实用儿科临床杂志

The main clinical phenotypes, imaging features and genetic test results of a child with Joubert syndrome treated in Shenzhen Children′s Hospital in July 2020 were analyzed retrospectively, and the literature on Joubert syndrome was summarized.The main manifestations of the protester during infancy were respiratory abnormalities and developmental retardation.The brain magnetic resonance imaging (MRI) showed a " molar sign" , which was consistent with the diagnosis of Joubert syndrome.Genetic testing suggested that the protestor carried complex heterozygous variations of KIAA0586 gene.Two variants were not reported previously, one of which was synonymous mutation.The child is the first case of Joubert syndrome caused by KIAA0586 gene in China.Joubert syndrome is a rare congenital brain development malformation characterized by high clinical heterogeneity and MRI molar signs.It may involve multiple systems.Early identification and intervention can improve outcomes.

Clinical, skeletal muscle pathological and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy / 中华实用儿科临床杂志

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

Analysis of clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody-positive myopathy / 中华实用儿科临床杂志

Objective:To explore clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive myopathy.Methods:Two cases of pediatric anti-HMGCR antibody-positive myopathy admitted to the Department of Neurology, Shenzhen Children′s Hospital from January to July 2020 were retrospectively analyzed for their clinical manifestations, creatine kinase (CK), myositis autoantibody, electromyography (EMG), muscle pathology, muscle magnetic resonance imaging (MRI), and treatment information.Results:Both of them were female cases.Case 1 was 3 years and 11 months old and case 2 was 7 years and 9 months old.They used to be healthy without history of statin use.Case 1 showed chronic onset of the disease, and case 2 had a subacute onset.The main clinical manifestations were progressive symmetric proximal muscle weakness accompanied by myalgia.Case 1 developed skin rash but case 2 did not.Significantly increased CK level was detected in both of them, which increased by 27.3-48.0 and 66.7-77.4 times of the upper limit before treatment in case 1 and case 2, respectively.They were diagnosed as muscular dystrophy at the early stage.EMG results suggested myogenic injuries in 2 cases, and muscle MRI showed extensive muscle edema.The muscle pathology of the 2 cases suggested muscle necrosis with a small amount of inflammatory cell infiltration.After diagnosis, both of them were treated with Methylprednisolone combined with intravenous immunoglobulin.CK decreased significantly but remained high, and muscle weakness was improved but did not return to normal.Oral Prednisone was given after discharge and case 2 was additionally medicated with azathioprine.Conclusions:Compared with adult patients, the clinical characteristics of pediatric anti-HMGCR antibody-positive myopathy are mostly similar.However, children patients usually have no history of statins and are more difficult to treat, less effective and worse prognosis.In addition, children patients are more likely to be diagnosed with " muscular dystrophy" at the beginning of illness.Therefore, idiopathic myositis autoantibody should be examined to confirm the diagnosis for children suspected to be " muscular dystrophy" but not confirmed by genetic examination.

Advance in application and efficacy of ketogenic diet therapy in drug-resistant epilepsy caused by gene mutation / 国际儿科学杂志

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

Diagnosis of angiostrongylus eosinophilic meningitis in infants by high-throughput sequencing: 2 cases of reports / 中华实用儿科临床杂志

Infants suffering from angiostrongylus eosinophilic meningitis (AEM) is rare, while AEM can cause severe consequences.The diagnostic value of high-throughput sequencing for AEM was studied by analyzing 2 AEM children (< 2 years old) in the Department of Neurology, Shenzhen Children′s Hospital in 2019.Case 1 mainly pre-sented intermittent fever, vomiting, mental fatigue and bregma bulge.Case 2 mainly manifested intermittent fever, cough, vomiting and convulsion.Due to hypereosinophils in patients′ peripheral blood and cerebrospinal fluid (CSF), and abundant DNA sequences from a cantonensis in CSF and positive antibody test, the patients were diagnosed with AEM.The patients were treated with albendazole to deworm, and small doses of methylprednisolone to reduce inflammation.The clinical characteristics of AEM infant are not typical, and high-throughput sequencing technology can assist the diagnosis of AEM.

Clinical and molecular genetic study on 21 children with lissencephaly / 中华实用儿科临床杂志

Objective:To study the clinical features and molecular genetic mechanisms of children with lissencephaly (LIS), as well as to analyze the relationship between genotypes and phenotypes of the disease.Methods:From October 2016 to December 2017, the clinical data and follow-ups of 21 LIS children were collected in the Department of Neurology, Shenzhen Children′s Hospital.Whole genome sequencing (WGS) was performed for genetic testing.Results:Among these 21 cases, 18 cases developed epilepsy (86%), and 3 cases were seizure free (14%). The onset age of children with epilepsy was relatively young, and 16 cases occurred within 1 year old (89%). Among these cases, 16 were pachygyria (76%), 3 cases were agyria combined with pachygyria (14%) and 2 cases were agyria (10%). Epileptic syndromes included 12 cases of West syndrome (67%), 2 cases of Ohtahara syndrome (11%), 2 cases of other epileptic encephalopathy (11%), and 2 cases of focal epilepsy (11%). Brain magnetic resonance imaging(MRI) demonstrated that most cases were pachygyria, among which diffuse pachygyria was more common (56%, 9/16 cases). The results of WGS: 13 pathogenic or likely pathogenic single nucleotide variants (SNV) and copy number variants (CNV) were detected.The total detection rate was 62%, of which 2 cases were frameshift, 1 case was nonsense and 1 case was missense variants of PAFAH1B1, 6 cases were chromosome 17p13.3 deletion syndrome, thus lea-ding to the whole gene deletion of PAFAH1B1, and 1 case was missense variant of DCX, frameshift variant of KIF2A, and missense variant of PIK3R2, respectively.Totally, 48% (10/21 cases) of the cases were variants or deletions of PAFAH1B1, which resulted in lissencephaly in the parietal-occipital region of the brain.Novel variants were PAFAH1B1: c.1067G>A, PAFAH1B1: c.897delT and KIF2A: c.2225delG. Conclusions:Most cases of LIS accompanied with epilepsy, in which West syndrome was relatively more common.Brain MRI showed that most cases were diffuse pachygyria.The variants and deletions of PAFAH1B1 was the main genetic cause of LIS.The identification of the novel variants expanded the genotypical spectrum of LIS.

Advances in the treatment of West syndrome with hormonal therapies / 国际儿科学杂志

West syndrome is one of the most common refractory epileptic syndromes with onsets mostly in infancy.The prognosis is generally poor.The morbidity rate reported in the literature is 0.2‰ to 0.5‰.Hormonal therapies(Adrenocorticotropic hormone and glucocorticosteroid)are recommended as preferred treatment options for West syndrome.It can effectively control spasms, ameliorate recognition impairment, and improve developmental outcomes.The incidence of side effects after hormonal therapy are high, and irritation, hypertension and infection are frequently reported.In this paper, advances in therapeutic mechanism, usage and dosage, short-term effectiveness, long-term effectiveness, prognosis and adverse effects of hormonal therapies are reviewed.

Examining geographical disparities in the incubation period of the COVID-19 infected cases in Shenzhen and Hefei, China

BACKGROUND@#Current studies on the COVID-19 depicted a general incubation period distribution and did not examine whether the incubation period distribution varies across patients living in different geographical locations with varying environmental attributes. Profiling the incubation distributions geographically help to determine the appropriate quarantine duration for different regions.@*METHODS@#This retrospective study mainly applied big data analytics and methodology, using the publicly accessible clinical report for patients (n = 543) confirmed as infected in Shenzhen and Hefei, China. Based on 217 patients on whom the incubation period could be identified by the epidemiological method. Statistical and econometric methods were employed to investigate how the incubation distributions varied between infected cases reported in Shenzhen and Hefei.@*RESULTS@#The median incubation period of the COVID-19 for all the 217 infected patients was 8 days (95% CI 7 to 9), while median values were 9 days in Shenzhen and 4 days in Hefei. The incubation period probably has an inverse U-shaped association with the meteorological temperature. The warmer condition in the winter of Shenzhen, average environmental temperature between 10 °C to 15 °C, may decrease viral virulence and result in more extended incubation periods.@*CONCLUSION@#Case studies of the COVID-19 outbreak in Shenzhen and Hefei indicated that the incubation period of COVID-19 had exhibited evident geographical disparities, although the pathological causality between meteorological conditions and incubation period deserves further investigation. Methodologies based on big data released by local public health authorities are applicable for identifying incubation period and relevant epidemiological research.

Research progress of ketogenic diet therapy for epilepsy associated with tuberous sclerosis complex / 中华实用儿科临床杂志

Tuberous sclerosis complex (TSC) is a hereditary and multisystemic disease, caused by mutations in the TSC1 or TSC2 gene, with an incidence of about 1/14 000 to 1/6 000.The neurological manifestations of TSC often include epilepsy, developmental delay, mental disorders and loss of neurological function.Among them, epilepsy is the most common manifestation, with an incidence of 80%-90%, 55%-62% of which is drug-resistant epilepsy.Epilepsy in TSC severely affects the clinical prognosis and life quality of patients.At present, epilepsy in TSC can be treated with the inhibitors of mammalian target of rapamycin(mTOR), antiepileptic drugs, ketogenic diet(KD), neuromodulation, palliative or resection operation.Although the exact mechanism of KD in the treatment of epilepsy in TSC is not clearly elucidated yet, it has been demonstrated in some studies that it is related to the inhibition of mTOR signaling pathway and other multiple mechanisms.Meanwhile, the safety and efficacy of KD therapy have been proven in many clinical studies.Therefore, KD is recommended for the treatment of epilepsy in TSC, especially when epilepsy is resis-tant to antiepileptic drugs, is not indicated for surgery or the surgery is ineffective.The research progress of the mechanism and clinical efficacy of KD therapy for epilepsy in TSC would be reviewed in this paper.

Research progress of anti-inflammatory mechanism of ketogenic diet / 中华实用儿科临床杂志

Composed by high fat, low carbohydrate, adequate protein and other nutrients, ketogenic diet (KD) is a kind of diet.KD simulates starvation has fatty acid metabolism to produce ketone body, thus providing energy in liver, and it has various functions such as anti-inflammation.KD has been used in nervous system diseases, but its mechanism is still not very clear.As a result, the review expounds KD mechanism of anti-inflammatory action from the inhibition of pathogenic microorganisms, adjusting intestinal flora, relieving pain and reducing oxidative stress in several aspects.

Application of scalp electroencephalogram in treatment of refractory epilepsy with vagus nerve stimulation / 生物医学工程学杂志

Electroencephalogram (EEG) has been an important tool for scientists to study epilepsy and evaluate the treatment of epilepsy for half a century, since epilepsy seizures are caused by the diffusion of excessive discharge of brain neurons. This paper reviews the clinical application of scalp EEG in the treatment of intractable epilepsy with vagus nerve stimulation (VNS) in the past 30 years. It mainly introduces the prediction of the therapeutic effect of VNS on intractable epilepsy based on EEG characteristics and the effect of VNS on EEG of patients with intractable epilepsy, and expounds some therapeutic mechanisms of VNS. For predicting the efficacy of VNS based on EEG characteristics, EEG characteristics such as epileptiform discharge, polarity of slow cortical potential changes, changes of EEG symmetry level and changes of EEG power spectrum are described. In view of the influence of VNS treatment on patients' EEG characteristics, the change of epileptiform discharge, power spectrum, synchrony, brain network and amplitude of event-related potential P300 are described. Although no representative EEG markers have been identified for clinical promotion, this review paves the way for prospective studies of larger patient populations in the future to better apply EEG to the clinical treatment of VNS, and provides ideas for predicting VNS efficacy, assessing VNS efficacy, and understanding VNS treatment mechanisms, with broad medical and scientific implications.

A resting-state functional magnetic resonance imaging study of altered brain function of benign epilepsy in children with central-temporal spikes / 中华实用儿科临床杂志

Objective:To analyze the brain functional fluctuation of benign epilepsy in children with central-temporal spikes(BECTS) by using ReHo algorithm based on the resting-state brain functional imaging, and to explore the connection of the brain function and changes of the connection pattern, so as to find the damage of the cognitive function of BECTS children in the early stage.Method:s Perspectiveness and simple random selection of 20 BECTS children and 20 healthy control children admitted to Shenzhen Children′s Hospital from January 2015 to December 2017 were conducted for basic information collection and functional magnetic resonance imaging (fMRI) testing in a resting-state.Result:s Significantly lower ReHo value appeared in the default mode network (DMN) area, and the precuneus (voxel=422, t=-5.085 6), cuneus (voxel=85, t=-4.240 3), angular gyrus (voxel=191, t=-4.681 2), cingulate cortex (voxel=313, t=-5.238 2), anterior central gyrus (voxel=12, t=-3.482 7), and supplementary motor area (voxel=1 356, t-6.596 2). The significantly increased ReHo was found in the bilateral cerebellum (voxel=71, t=5.658 2), right superior temporal gyrus (voxel=24, t= 5.184 0), operculum insulae (voxel=337, t=6.814 9), left parietal lobe (voxel=12, t=4.378 7), and inferior parietal lobule (voxel=11, t=3.433 7). Conclusions:Significant impairment of DMN, Wernicke and angular gyrus functions in BECTS children may be one of the mechanisms of cognitive dysfunction.Enhanced sensorimotor area and cortical brain functions near the operculum insulae and central sulcus lead to seizures with typical clinical symptoms.fMRI has a high specificity and sensitivity for evaluating the brain function of children with BECTS, and it can detect the impairment of cognitive function in children with this type of epilepsy at an early stage.

Research progress of ketone bodies in ketogenic diet therapy of epilepsy / 中华实用儿科临床杂志

Ketogenic dietary therapy (KDT) is a kind of formulated diet with high fat,low carbohydrates,and appropriate protein and other nutrients,which is mainly used for the treatment of intractable epilepsy in children.The main metabolic change in the body during KDT is the production of a large number of ketone bodies which can not only provide energy,but also plays an important role in inhibiting the transmission of abnormal excitatory signals in the brain.However,the anti-epileptic mechanism of ketone bodies in KDT is still not very clear.Some clinical studies have found that the level of blood ketone is inconsistent with the effect of epilepsy control.The latest progress of research on the synthesis,monitoring,effective concentration range and the relationship with efficacy of ketone bodies in ketogenic diet therapy are reviewed in this article,in order to provide reference blood ketone range in clinical ketogenic diet.

Research progress of ketone bodies in ketogenic diet therapy of epilepsy / 中华实用儿科临床杂志

Ketogenic dietary therapy (KDT) is a kind of formulated diet with high fat, low carbohydrates, and appropriate protein and other nutrients, which is mainly used for the treatment of intractable epilepsy in children.The main metabolic change in the body during KDT is the production of a large number of ketone bodies which can not only provide energy, but also plays an important role in inhibiting the transmission of abnormal excitatory signals in the brain.However, the anti-epileptic mechanism of ketone bodies in KDT is still not very clear.Some clinical studies have found that the level of blood ketone is inconsistent with the effect of epilepsy control.The latest progress of research on the synthesis, monitoring, effective concentration range and the relationship with efficacy of ketone bodies in ketogenic diet therapy are reviewed in this article, in order to provide reference blood ketone range in clinical ketogenic diet.

Prospective control study of efficacy and safety of ketogenic diet on drug refractory Dravet syndrome / 中华实用儿科临床杂志

Objective@#To investigate the efficacy and safety of ketogenic diet (KD) and antiepileptic drugs(AEDs) in the children with drug refractory Dravet syndrome (DS).@*Methods@#Thirty-two cases of drug refractory DS were enrolled into the Department of Neurology, Shenzhen Children′s Hospital Affiliated to Shantou University Medical School from July 2016 to December 2017, and they were divided into 2 groups: KD group and AEDs group (16 cases for each group), respectively.KD was added to as an additional therapy for KD group, and oral AEDs were administered only in AEDs group.In KD group, oral AEDs were not adjusted for the first 3 months.AEDs could be adjusted within a limited range in 2 groups after 3 months.The clinical efficacy, improvement of cognitive function, retention rate and side effects were observed and compared after 3, 6, 12 months of treatment.The average monthly seizure frequency within 3 months before enrollment was recorded as the baseline.The clinical efficacy was assessed by comparing the seizure frequency of each observation period with the baseline.@*Results@#In KD group, after 3, 6, 12 months′ follow-up, KD the-rapy was maintained in 15, 14, 12 patients.The number of patients whose seizure reduction over 50% was 10, 12, 11 cases, respectively.The number of patients whose seizure reduction over 90% was 7, 9, 10 cases, respectively.The number of patients who were seizure free was 3, 6, 8 cases, respectively.In AEDs group, after 3, 6, 12 months′ therapy, the number of patients whose seizure reduction over 50% was 6, 7, 8 cases, respectively, the number of patients whose seizure reduction over 90% was 3, 3, 4 cases, respectively.The number of patients who were seizure-free was 2, 1, 2 cases, respectively.There was a significant difference in the seizure reduction between 2 groups after 6, 12 months (P<0.05). Furthermore, the incidence of status epilepticus (SE) was significantly reduced in KD group, and non-fever related status epilepticus (NFSE) was preferentially improved.There was a significant difference in the incidence of SE between before and after treatment in the KD group (P<0.05). After 12 months, there was a significant difference in the incidence of SE between 2 groups (P<0.05). After 6, 12 months of treatment, the patients in KD group had significant improvements in adaption, gross motor and language quotients by Gesell Developmental Scale compared to the AEDs group (all P<0.05). Eleven of 12 children who adhered to the therapy for 1 year in KD group had improvement of developmental quotient ≥ 1 grade, however, 7 cases of 16 children in AEDs group had this improvement.The incidence of adverse effect in the KD group and the AEDs group was 37.5%(6/16 cases) and 56.3%(9/16 cases), respectively, and the difference was not significant (P>0.05).@*Conclusions@#KD can not only reduce seizure frequency and relieve SE, but also improve the cognitive function of drug refractory DS.The adverse reaction ratio of KD does not increase significantly compared to AEDs.Therefore, KD is effective and safe therapy for children with drug-resistant DS.

Prospective control study of efficacy and safety of ketogenic diet on drug refractory Dravet syndrome / 中华实用儿科临床杂志

Objective To investigate the efficacy and safety of ketogenic diet (KD) and antiepileptic drugs (AEDs) in the children with drug refractory Dravet syndrome (DS).Methods Thirty-two cases of drug refractory DS were enrolled into the Department of Neurology,Shenzhen Children's Hospital Affiliated to Shantou University Medical School from July 2016 to December 2017,and they were divided into 2 groups:KD group and AEDs group (16 cases for each group),respectively.KD was added to as an additional therapy for KD group,and oral AEDs were administered only in AEDs group.In KD group,oral AEDs were not adjusted for the first 3 months.AEDs could be adjusted within a limited range in 2 groups after 3 months.The clinical efficacy,improvement of cognitive function,retention rate and side effects were observed and compared after 3,6,12 months of treatment.The average monthly seizure frequency within 3 months before enrollment was recorded as the baseline.The clinical efficacy was assessed by comparing the seizure frequency of each observation period with the baseline.Results In KD group,after 3,6,12 months' follow-up,KD therapy was maintained in 15,14,12 patients.The number of patients whose seizure reduction over 50％ was 10,12,11 cases,respectively.The number of patients whose seizure reduction over 90％ was 7,9,10 cases,respectively.The number of patients who were seizure free was 3,6,8 cases,respectively.In AEDs group,after 3,6,12 months' therapy,the number of patients whose seizure reduction over 50％ was 6,7,8 cases,respectively,the number of patients whose seizure reduction over 90％ was 3,3,4 cases,respectively.The number of patients who were seizure-free was 2,1,2 cases,respectively.There was a significant difference in the seizure reduction between 2 groups after 6,12 months (P ＜ 0.05).Furthermore,the incidence of status epilepticus (SE) was significantly reduced in KD group,and non-fever related status epilepticus (NFSE) was preferentially improved.There was a significant difference in the incidence of SE between before and after treatment in the KD group (P ＜ 0.05).After 12 months,there was a significant difference in the incidence of SE between 2 groups (P ＜ 0.05).After 6,12 months of treatment,the patients in KD group had significant improvements in adaption,gross motor and language quotients by Gesell Developmental Scale compared to the AEDs group (all P ＜ 0.05).Eleven of 12 children who adhered to the therapy for 1 year in KD group had improvement of developmental quotient ≥ 1 grade,however,7 cases of 16 children in AEDs group had this improvement.The incidence of adverse effect in the KD group and the AEDs group was 37.5％ (6/16 cases) and 56.3％ (9/16 cases),respectively,and the difference was not significant (P ＞ 0.05).Conclusions KD can not only reduce seizure frequency and relieve SE,but also improve the cognitive function of drug refractory DS.The adverse reaction ratio of KD does not increase significantly compared to AEDs.Therefore,KD is effective and safe therapy for children with drug-resistant DS.

Clinical features and genetic analysis of a case with carnitine palmitoyltransferase 1A deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency.</p><p><b>METHODS</b>Clinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing.</p><p><b>RESULTS</b>Analysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function.</p><p><b>CONCLUSION</b>Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.</p>

Diagnosis and treatment of nonconvulsive status epilepticus in children / 中华实用儿科临床杂志

The Neurocritical Care Society′s Guidelines for the Evaluation and Management of Status Epilepti-cus defines status epilepticus as the epilepsy lasts for 5 minutes or longer,with continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery (returning to baseline) between seizures.Nonconvulsive status epilepticus (NCSE) can be classified into with or without coma/stupor types.The diagnosis of NCSE needs continuous video electroencephalogram monitoring and the indications include:(1) altered mental status appear after seizures,acute brain injury or other unknown causes;(2)efficacy evaluation of seizure therapy is performed to confirm whether nonconvulsive seizures or NCSE is controlled monitoring for 24 to 48 hours;(3)identification of cerebral ischemia.Modified Salzburg consensus criteria for NCSE suggests that the diagnosis of NCSE needs the combination of clinical features and electroencephalograms.Suspected clinical features and signs of NCSE should last at least 10 minutes,and altered EEG of suspected NCSE should last at least 10 seconds.Benzodiazepines is the first choice of treatment in NCSE and antiepileptic drugs are selected if necessary.If the NCSE lasts longer than 60 minutes,anesthetics or other therapies may be administered.

Clinical and genetic analysis of a family with familiar acute necrotizing encephalopathy due to mutation in the RANBP2 gene / 中华实用儿科临床杂志

Objective To analyze the clinical manifestations of familial acute necrotizing encephalopathy (ANE)and to improve the recognition of this disease. Methods The clinical data of a 25 - month - old girl with fa-milial and recurrent ANE with evidence of mutation in the RANBP2 gene were collected and analyzed,and the gene examination of their family members was performed. Results A previously healthy girl experienced recurrent ANE epi-sodes at the ages of 8 months,18 months and 25 months,respectively. At each beginning of each episodes the patient presented with lethargy and tremor of limbs following febrile illness of 3 - 4 days,even developed coma and convulsions in the last time. Brain magnetic resonance imaging showed bilateral and high T2 signal changes in thalamus,cerebellum and hippocampus. Abnormal signals also appeared in the brainstem,claustrum,corpus scallosum and cortex(temporal, parietal and cingulate)also appeared abnormal signals. Spinal MRI showed spinal cord involvement. The girl recovered after her first episode;she could speak but could not walk steadily after the second time;after the third episode,al-though she regained consciousness from coma,she could no longer speak or walk. The patient's sister died of encephali-tis at the age of 18 months. Her paternal uncle had suffered from dysnoesia from meningitis at his 17 months of age. The patient and her grandmother,father,uncle and one of her aunts harbored a mutation(c. 1754C ﹥ T)in RANBP2 gene. Conclusions Familial ANE has typical clinical manifestations and characteristic MRI findings. The patient with recur-rent history,especially with positive family history,should have the mutation in RANBP2 gene detected earlier in order to clarify the diagnosis of ANE.