Analysis of clinical phenotype and genotype of children with centronuclear myopathy and follow-up study / 中华实用儿科临床杂志

Objective:To investigate the phenotype, genotype and clinical course of centronuclear myopathy(CNM) in children.Methods:Clinical data of patients with CNM in the Department of Pediatrics, Peking University First Hospital from October 2008 to December 2018 were collected.The clinical, pathological and genetic data of 9 children with CNM were retrospectively analyzed.The patients were followed up from 8 months to 8.6 years [(4.4±3.1) years].Results:(1)Clinical phenotype: there were 6 males and 3 females with onset age ranging from 1 d to 10 years.Generalized muscle weakness or motor retardation was the main complaint in 8 cases, while elevated muscle enzymes presented in 1 case.Varying degrees of skeletal muscle weakness were noted on examination in all patients, with facial muscle involvement in 4 cases.Six patients were followed up.No deterioration in motor function was noted, while 2 patients had improvement.There was no significant cardiac involvement in all 6 patients.Scoliosis occurred in 4 patients.Restrictive ventilator disorder developed in 2 out of the 5 patients who underwent pulmonary function tests.(2)Genotype: 8 out of 9 patients underwent gene test, confirmed gene diagnosis in 4 patients including: DNM2 gene (c.1856C>T, c.1893+ 1G>A was novel) de novo heterozygous mutation in 2 cases, RYR1 gene (c.2044C>G, c.6823G>A, both were novel) compound heterozygous mutation in 1 case, and TTN gene (c.107377+ 1G>A, c.2106_2107 insAAGCTGTA was novel) compound heterozygous mutation in 1 case. Conclusions:The course of centronuclear myopathy is relatively static, with more frequent involvement of facial muscles than myocardium.This study enriched the gene mutation spectrum of centronuclear myopathy (4 novel mutations).

Clinical analysis of neuromyelitis optica spectrum disorders in childhood / 中华儿科杂志

Objective@#To explore clinical features and the effect of treatment of neuromyelitis optica spectrum disorders (NMOSD) in childhood.@*Methods@#Children who were hospitalized in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2018 and meeting diagnostic criteria of NMOSD proposed by the International Panel for NMOSD Diagnosis in 2015 were summarized and followed up. The basic information, symptoms of each attack, locations and patterns of new lesions, features of cerebrospinal fluid, serologic markers, treatments and outcomes in these patients were analyzed. Thirty-three children were included in the study, with 13 males and 20 females. The median age of onset was 6.83 (4.25, 8.75) years. Compared aquaporin-4 immunoglobulin G (AQP4-IgG) associated NMOSD with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) associated NMOSD. Mann-Whitney U test was used for continuous variables and Fisher test for categorical variables in comparison between AQP4-IgG and MOG-IgG associated NMOSD. Wilcoxon test was used for annualized relapse rate (ARR) before and after adding disease-modifying drugs.@*Results@#Optic neuritis (39% (13/33) in initial attacks and 49% (62/127) in total attacks) and myelitis (36% (12/33) in initial attacks and 26% (33/127) in total attacks) were the top two symptoms in both the initial attacks and all 127 attacks during follow-up. There was 42% (37/89) of brain magnetic resonance imaging (MRI) scans in acute phase showing new lesions in supratentorial white matter, with 43% (16/37) showing acute disseminated encepha lomyelitis (ADEM)-like or leukodystrophy-like patterns. AQP4-IgG was detected in 30% (10/33) patients, and MOG-IgG was detected in 55% (11/20) patients, with no combined positive case. In 20 patients treated with rituximab, two were treated after the initial attack. In the other 18 patients, the median annualized relapse rate decreased from 1.86 (1.52, 2.60) before treatment to 0.28 (0, 1.13) during treatment (Z=-3.376, P=0.001). Compared with AQP4-IgG associated NMOSD (10 cases), fever of unknown origin (8/40 vs. 0/33, P=0.007) was more common, area postrema syndrome (0/40 vs. 4/33, P=0.038) was fewer, cell count of cerebrospinal fluid (49.0 (17.5, 115.0) ×106/L vs. 5.5 (3.0, 15.8)×106/L, Z=-3.526, P=0.000) was higher in MOG-IgG associated NMOSD (11 cases).@*Conclusions@#In childhood-onset NMOSD, optic neuritis and myelitis were top two symptoms. Childhood-onset NMOSD has high proportion of positive MOG-IgG. Lesions in supratentorial white matter are common. Rituximab could significantly decrease ARR of NMOSD in childhood. However, more studies should be conducted to explore the optimal treatment strategy in different antibody associated NMOSD.

Application of high-dose Diazepam in epileptic children with electrical status epilepticus during sleep / 中华实用儿科临床杂志

Objective To explore the therapeutic effects and adverse reaction of high-dose Diazepam (DZP) in patients with electrical status epilepticus during sleep (ESES).Methods Nine patients in the Outpatient of the Department of Pediatrics,Peking University First Hospital from October 2016 to May 2017 with ESES were treated with high-dose DZP.Oral DZP was administered in a dose of 0.75-1.00 mg/kg(maximum:40 mg) during the first night followed by 0.5 mg/(kg · d) (maximum:20 mg) from the second night for 1-3 months and tapered over next 1-3 months.The seizures,electroencephalogram (EEG) changes and adverse reactions were observed before and after DZP treatment.Results Six of 9 patients were male and 3 were female.The age of onset was ranged from 1 year and 6 months to 10 years.Benign childhood epilepsy with central temporal spike was diagnosed in 5 cases,epileptic encephalopathy with continuous spike-and-wave during sleep in 1 case,and ESES related epilepsy in 3 cases.Age of onset DZP treatment ranged from 4 years and 4 months to 12 years,and the duration of DZP treatment was ranged from 1 to 5 months (1 case only for the first night).The follow-up interval was 6-12 months.The efficiency of DZP on seizures:intent effective in 5 patients,effective in 2 patients and ineffective in 2 patients,and the effective rate was 78％ (7/9 cases).The efficiency of DZP on EEG (1 month after DZP treatment):intent effective in 2 patients (EEG normalized),effect in 3 patients and no effect in 2 patients,and the effective rate was 71％ (5/7 cases),while 2 patients did not receive EEG examination.Four of 7 patients (57％) with intent effect and effective of DZP on seizures had seizures relapse during drug reduction and after drug withdrawal,and the EEG deteriorated simultaneously.Adverse reactions of DZP included 3 patients (33％) with adverse reactions,bed-wetting in 2 patients and snoring on the first night in 1 patient who withdrew DZP later.Conclusions The high-dose of DZP has a certain effect on seizures control and ESES suppression in patients with ESES,but also has a certain recurrence rate.The adverse reactions are mild and self-limiting.High-dose DZP treatment could be a choice for refractory patients with ESES to alleviate disease.

Clinical and electroencephalogram features of neuronal ceroid lipofuscinosis / 中华实用儿科临床杂志

Objective To summarize the clinical and electroencephalogram features of neuronal ceroid lipofus-cinosis (NCL). Methods A retrospective analysis of the clinical phenotypes and electroencephalogram features of pa-tients diagnosed with NCL in Department of Pediatrics,Peking University First Hospital from February 2000 to August 2015 were conducted. Results Among the 30 patients,18 were male and 12 were female. The age of onset was between 9 months to 7 years old. The first symptoms included seizure in 22 patients,psychomotor developmental delay or regre-ssion in 7 cases,and visual loss in 1 case. Clinical manifestations included psychomotor regression in 29 cases,epilepsy in 28 cases,visual impairment in 19 cases,ataxia in 20 patients,and positive pyramidal tract sign in 13 cases. Twenty-one patients accepted fundus oculi examination. Seven patients were found with macular degeneration,8 cases with optic nerve atrophy,2 cases with retinal pigment degeneration,and 8 patients were normal. Brain atrophy were found in all 30 cases,including diffuse brain atrophy in 14 cases,only cerebellar atrophy in 6 cases,and cerebral atrophy with periven-tricular T2W high signal in 10 cases. Video electroencephalogram(EEG)examination was performed in 27 patients and their backgrounds were diffuse slow waves. Seven patients didn't have physiological vertex sharp waves or sleep spin-dles. Generalized epileptiform discharges were captured in 6 cases,focal epileptiform discharges in 15 cases. Both of generalized and focal epileptiform discharges were captured in 6 cases. Generalized slow wave burst in 4 cases,and in-termittent photic stimulation evoked epileptiform discharges in 3 cases. Ten patients were observed with clinical sei-zures,including 4 cases of myoclonic episodes,3 cases of atypical absences,3 cases of focal seizures,1 case of atonic and one of tonic spasms. Peripheral blood enzyme examination was taken in 13 patients,among whom 8 patients were identified with tripeptidyl peptidase 1 (TPP1)deficiency and 1 patient with palmitoyl protein thioesterase 1 (PPT1) deficiency. Twenty-eight patients accepted skin and/or muscle electron microscope examination. Osmiophilic granular was found in 2 cases,curvilinear bodies in 15 cases,fingerprint profiles in 2 cases,curvilinear and linear bodies in 1 case,fingerprint profiles and osmiophilic granular in 1 case. NCL-related gene detection was conducted in 3 patients, with 1 patient identified with CLN6 compound heterozygous mutations and 2 patients with TPP1 homozygous mutations. Thirty patients were classified into 3 groups based on the onset age,enzymatic examination results and pathological examination of skin and muscle,including 5 cases of infantile NCL,20 cases of late-infantile NCL,and 5 cases of juvenile NCL. Conclusions The clinical features of NCL included multiple types of epileptic seizures (among which myoclonus was the most common type),psychomotor developmental delay or regression,vision loss,ataxia,and positive pyramidal tract sign. Its MRI was characterized with brain atrophy. EEG showed diffuse slow wave activity,with focal and/or generalized epileptiform discharges. Specific enzyme examination,and skin or muscle pathology or gene test could help to make diagnosis.

A case report of childhood Farber′s disease and literature review / 中华儿科杂志

Objective@#To explore the clinical features, diagnosis, treatment and the prognosis of Farber disease by case report and literature review.@*Method@#The clinical information of a case with farber′s disease diagnosed in October 2015 at Peking University First Hospital was collected and analyzed, including clinical manifestation, electrophysiology, magnetic resonance imaging, pathology, treatments and prognosis.ASAH1 gene mutational analysis was conducted in the patient and her parents.By using "Farber′s disease, ASAH1" as keywords, literature was searched from Pubmed, CHKD and HGMD database from January 1951 to January 2016.@*Result@#The girl, 2 years 2 months old, was sent to our hospital in October 2015, with complains of "joint swelling for 17 months, development regress of intelligence and movement for 11 months, intermittent seizures for 2 months" .The clinical manifestation of the patient was characterized by painful and deformed joints, subcutaneous nodules, progressive hoarseness, and the progressive neurological system deterioration.Joints swelling and deformity behave as the first symptoms.A series of electroencephalogram showed slow background and spike wave.Visual evoked potential was significantly abnormal.Brain magnetic resonance imaging (MRI) showed hypomyelination and progressive diffuse brain atrophy.Histology of subcutaneous nodule showed proliferation of the connective tissue with hyalinization, cholesterol crystal like changes, and a large number of foamy cell infiltration.Compound heterozygous mutations of ASAH1 gene, c. 304_305 ins A (p.T102Nfs14) and c. 314T>C (p.L105p), were found in the patient, and the former is inherited from her mother, the latter from her father.Antiepileptic treatment and other symptomatic treatments were delivered to the patient, but the effectiveness was poor.One reference from China hownet and 35 references from Pubmed have reported a total of 26 cases.Twenty out of 26 patients (77%) had the onset under 1 year of age.By region, there were 12 patients (12/26, 46%) from India, and the others around world.Among these 12 indian patients, 10 lack of complete clinical data.Among the rest 16 patients, 4 patients′ parents were consanguineous; 8 patients with the main clinical manifestation of painful and deformed joints, subcutaneous nodules, and hoarse cry; 4 patients with hepatic failure and impaired spleen; 5 patients with rapid neurological deterioration; 1 patient with bone destruction; 7 patients under liver and skin biopsies, pathologically showing a large number of foam cells and "Farber bodies" . There are 33 genetic mutations, and 45% (15/33) mutations are concentrated in ASAH1 exon 6-10.@*Conclusion@#Farber disease is a rare autosomal recessive disease caused by deficiency of lysosomal acid ceramidase.Histopathology of granulomatous tissue plays an important role in the early diagnosis.

Peripheral nerve injury in LAMA2-related congenital muscular dystrophy patients / 中华儿科杂志

Objective@#To explore the injury pattern and features of peripheral nerve in congenital muscular dystrophy patients caused by LAMA2 gene mutation.@*Method@#Seventeen patients genetically or molecular pathologically diagnosed as LAMA2-related congenital muscular dystrophy were recruited in Peking University First Hospital between 2002 and 2015. All the patients received nerve conduction velocity (NCV) and needle electromyography tests. Clinical and laboratory examination data of the patients was retrospectively analyzed. The correlation between the NCV and disease course was determined by Pearson correlation analysis. Additionally, one patient underwent a sural nerve biopsy.@*Result@#Among these 17 identified patients (13 male and 4 female), all of them were diagnosed as congenital muscular dystrophy, and all of them underwent electrophysiological examination at ages between 1 month to 6 years. Electromyogram indicated seventeen patients of myogenic damage, of whom 10 cases were complicated with reduced NCV. Twenty-six of 95 analyzed nerves showed NCV slower than the normal average of contemporary in 17%-47%. Correlation analysis between NCV and the disease course indicated that NCV of median nerves, ulnar nerves, tibial nerves and common peroneal nerves were negatively associated with the disease course (r=-0.737, -0.771, -0.540 and -0.682, respectively; all P<0.05). Sural nerve biopsy revealed peripheral neuropathy changes of myelin.@*Conclusion@#There is peripheral nerve injury in LAMA2-related muscular dystrophy patients. It mainly manifests as demyelinating lesions. Moreover, the NCV of peripheral nerve will decrease with the increase of the course of the disease.

Diagnosis and therapy of congenital myopathies / 中华实用儿科临床杂志

Congenital myopathies are a group of genetic muscle disorders with a relatively non-progressive clinical course,characterized by weakness and hypotonia of varying severity,morphologically recognized by specific structural abnormalities within the myofibers.The diagnosis of congenital myopathies mainly based on characterized clinical manifestation and histological features on muscle biopsy.The genetic basis of many different forms of the congenital myopathies has been identified,while there are still more genes to be discovered.Until now,the main management of congenital myopathies was to alleviate complications arising from weakness of various muscle groups.

TK2-related mitochondrial DNA depletion syndrome:two cases report and review of literature / 中华实用儿科临床杂志

Objective To study the clinical characteristics,muscle pathological features,diagnosis and prognosis of TK2-related mitochondrial DNA depletion syndrome(MDS).Methods Clinical and laboratory data of 2 cases of TK2-related myopathic MDS were reported.And data of previously reported 58 TK2-related MDS cases were reviewed.Results Total 60 patients consisted of 35 male and 25 female.The age of onset ranged from the birth to the age of 74 years old,and 54 of the patients were attacked at the age younger than 3 years old.Muscle weakness and hypotonia were detected in all patients,with 40 patients(including the newly diagnosed 2 cases) manifested as pure myopathic form,and 20 patients with other multiple organs involvement.Serum creatine kinase was mildly increased (211-6 500 IU/L) in 53 patients.Elevated serum lactic acid level (2.3-12.0 mmol/L)was observed in 24 patients.Muscle biopsy was available from 55 patients,and ragged red fibers and/or cytochrome C oxidase (COX)-negative fibers were detected in 48 out of them.Nine out of 11 patients received electronic microscope study showed proliferation of abnormal mitochondria.Respiratory chain enzymatic activities in skeletal muscle were reduced in 31 out of 33 patients.Marked mtDNA content reduction was observed in 36 out of 41 patients (4％-25％ of age-and tissue-matched controls).A total of 42 TK2 mutations were found in 60 patients,including 2 novel mutations c.923A ＞ G and c.619-2A ＞ T in this study.Conclusions The most common clinical manifestations of TK2-related MDS are severely,rapidly progressing myopathy with infantile or early childhood onset.As the detection rate of characteristic pathologic features in muscle is high,muscle biopsy is important for the diagnosis of TK2-related MDS.

Efficacy of methylprednisolone therapy for electrical status epilepticus during sleep in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of methylprednisolone for electrical status epilepticus during sleep (ESES) in children.</p><p><b>METHOD</b>The clinical and EEG data of 82 epilepsy patients with ESES, which included benign childhood epilepsy with centro temporal spikes (BECT) variants, epilepsy with continuous spikes and waves during slow sleep (CSWS) , Landau-Kleffner syndrome (LKS) collected from department of pediatrics, Peking University First Hospital were analyzed from July 2007 to September 2012. During ESES period, all patients received methylprednisolone treatment for three courses, which included methylprednisolone intravenous infusion for three days, followed by oral prednisone for four days every time. After three courses, prednisone [1-2 mg/(kg × d)] were taken by all patients for 6 months. The ESES phenomenon and seizures were observed before and after treatment. The efficacy of corticosteroid on ESES suppression, seizure control of three epilepsy syndrome were analyzed.</p><p><b>RESULT</b>Thirty-nine cases were male and 43 cases were female. The epilepsy syndromes included 49 patients diagnosed as benign childhood epilepsy with centrotemporal spike (BECT) variants, 27 patients diagnosed as epilepsy with continuous spikes and waves during slow sleep (CSWS), and 6 patients diagnosed as LKS. Age of onset ranged from 1 year and 4 months to 11 years. The age of ESES newly monitored was from 2 years to 10 years and 8 months. The total effective rate of corticosteroid was 83% (68/82) for ESES, BECT variants was 82% (40/49), CSWS was 81% (22/27), LKS was 100% (6/6). There was no statistically significant difference in effective rates between the front two (χ² = 0.09, P > 0.05). The seizures were improved in the first month after methylprednisolone treatment in 3 epilepsy syndromes. The recurrence rate of BECT variants was 47% (23/49) , CSWS was 59% (16/27) , LKS was 50% (3/6) after 1 year follow up. There was no association between disease parameters, including age at seizure onset, duration of ESES and the treatment effect of ESES examined by Kruskal-Wallis method (χ² = 3.585, 0.932, P > 0.05).</p><p><b>CONCLUSION</b>Methylprednisolone was effective for improving ESES and seizures in 3 epilepsy syndromes combined with ESES. There was no significant correlation between age at seizure onset, duration of ESES and treatment effect of ESES.</p>

Study on concordance of ictal and interictal epileptiform activity in patients with tuberous sclerosis complex / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the relationship between the ictal onset zone and dominant interictal epileptiform foci in tuberous sclerosis complex (TSC) patients.</p><p><b>METHOD</b>Clinical data of 20 patients with TSC which had epileptic seizures during Video-EEG monitoring was assessed. Consistency and dominance of focal interictal epileptiform activity and the ictal onset zone were identified. Concordance between interictal and ictal findings was analyzed.</p><p><b>RESULT</b>Of the 20 patients, 7 were female, and 13 were male. The age of epilepsy onset was from 15 d to 6 years. The Video-EEG monitoring age was from 6 months to 11 years. Family history was found in three cases. Abnormality in neuroimaging existed in 17 of 18 patients who were examined. Interictal EEG showed hypsarrhythmia in 3 patients, multifocal epileptiform activity with a dominant focus in 12 patients, both focal and generalized discharges in 2 patients, and only focal discharges in 3 patients. The seizures types during EEG monitoring included epileptic spasms, partial seizure, atypical absence, and generalized or focal myoclonic seizure. The most common seizure type was partial seizure and then epileptic spasms. EEG in 4 patients with epileptic spasms showed ictal generalized discharges and interictal hypsarrhythmia or generalized discharges. Clinical manifestation of epileptic spasms was asymmetric in 3 patients. Lateralization and location of interictal and ictal discharges were consistent in 2 of the 3 patients, while only lateralization consistency in 1 of the 3 patients. Partial seizures as the only seizure type were monitored in 13 patients. Of the 13 patients, lateralization and location of interictal and ictal discharges were inconsistent in 2 patients (15%), consistent in 8 patients (62%), lateralization or location consistent in 2 patients (15%). One case could not be analyzed because of uncertainty of lateralization and location of seizure onset.</p><p><b>CONCLUSION</b>In the majority of patients with TSC, multifocal interictal epileptiform activity is present, in which a most dominance of focal epileptiform activity could be found. For some epileptic seizures or the majority of partial seizures, the ictal onset zone is concordant with the dominance of focal interictal epileptiform foci. The concordance might have positioning reference significance for preoperative evaluation of epilepsy surgery.</p>

Clinical, molecular pathological and genetic analyses of a Chinese family with congenital muscular dystrophy type 1A / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze and characterize the clinical, molecular pathological and genetic features of a Chinese family with congenital muscular dystrophy type 1A (MDC1A).</p><p><b>METHODS</b>Clinical data of the proband and her family members were collected. Immunohistochemistry staining was performed on muscular biopsy tissues with anti-merosin, alpha-dystroglycan, beta-dystroglycan and dystrophin antibodies. Genomic DNAs from the patient and her parents were extracted using standard procedures from the peripheral blood leukocytes. PCR and DNA direct sequencing were employed to analyze all of the 65 exons of the LAMA2 gene to determine the gene mutation, and the relationships between genotype and phenotype were analyzed.</p><p><b>RESULTS</b>The proband presented with delayed motor development and a myopathic face. Her midrange elevated serum creatine kinase (CK) levels and white matter signal intensity changes are consistent with MDC1A, and was clinically diagnosed as MDC1A. The immunohistochemistry analysis for the proband exhibited complete loss of merosin staining. Further test with PCR detected a homozygous mutation of c.817A>T in exon 5, while her parents were heterozygotes for the mutation.</p><p><b>CONCLUSION</b>The authors have defined the clinical manifestation of the Chinese family with MDC1A. The proband carried a homozygous nonsense mutation c.817A>T, and her parents were heterozygous carriers, consistent with autosomal recessive inheritance.</p>

Effect of naloxone on remote seizure susceptibility / 北京大学学报(医学版)

Objective : To evaluate the effect of low dose naloxone on remote seizure susceptibility after repeated febrile seizures(FS) in developing age. Methods: Warm water induced rat FS model was developed in this study.Forty nine SD rats were randomly divided into two groups: normal control group( n =10) and hyperthermic seizure group( n =39).The latter was further divided into FS control group( n =13) and naloxone treated group( n =26). The dose of naloxone was different in the two naloxone treated groups(13/each group). One group dose was 1 mg/kg, and the other 2 mg/kg. Each rat of hyperthermic seizure groups was induced to have 7 febrile seizures at the interval of 1 day. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone treated group, while the rats of other groups were injected with 0.9% sodium chloride. After the seventh stimulation, all rats were left un stimulated for 2 months, then re stimulated. Re stimulated seizureincidence rate, seizure duration and seizure grade in different groups were observed and compared with each other. Hippocampal mossy fiber sprouting was detected by Timm stain. Results: In naloxone treated group, the rats'seizure duration and seizure grade [(5.66?2.78) min,(2.97? 1.18)] significantly decreased ( t =5.035, P

Hypertension and erythromelalgia as prominent manifestations of mercury intoxication / 北京大学学报(医学版)

SUMMARY Mercury intoxication is a rare cause of severe hypertension. A case of mercury intoxication presented with severe hypertension and erythromelalgia was reported. A 10-year-and-5-month-old girl presented with recurrent rash and painful hands for 2 months, with seizure attack and episodic loss of consciousness for one hand half months. The girl was found to have red painful hands, a blood pressure 170/120 mm Hg(1 mm Hg=0.133 kPa), tachycardia and hypokalemia (2.83-3.25 mmol/L, reference value 3.5-5.5 mmol/L). An extensive investigation ensued. Elevated renin-angiotensin and aldosterone were demonstrated in plasma. Cranial MRI T2 weighed images showed widespread white matter signal abnormalities, which particularly involved parietal, occipital and frontal lobes. With hypertension controlled, white matter signal abnormalities weakened. Other symptoms included insomnia, nausea and paroxysmal abdominal pain. The girl was found to have a raised concentration of mercury in urine (0.171 mg/L, reference value

Alteration of hydrogen sulfide/cystathionine-?-synthase system in rats with recurrent febrile seizures / 北京大学学报(医学版)

Objective: To study the alteration of hydrogen sulfide (H_2S)/ cystathionine-?-synthase (CBS) system during recurrent febrile seizures (FS) in the hippocampus of developing rats. Methods: The rats were randomly divided into control group (n=8) and hyperthermia-treated group (n=22). Which was subdivided into FS group (n=8) and H group(no seizure occurred, n=9) according to whether seizures occurred. The plasma level of H_2S was detected by the spectrophotometer. The expression levels of CBS gene and protein were examined by in situ hybridization and immunohistochemistry respectively. Results: The plasma levels of H_2S were increased significantly in FS group compared with those of control group or H group. The expression levels of CBS gene and protein were enhanced in FS group compared with those of control group or H group. Conclusion: The expression levels of H_2S/ CBS system were up-regulated during recurrent FS.