Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm / 中国当代儿科杂志

OBJECTIVES@#To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS).@*METHODS@#A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity.@*RESULTS@#Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05).@*CONCLUSIONS@#Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

Newest etiology of infantile spasms syndrome / 中华实用儿科临床杂志

Infantile spasms syndrome (ISs) is a kind of catastrophic epileptic encephalopathy.Epileptic spasms originating in infancy or early childhood, typically accompanied by an electroencephalographic pattern of hypsarrhythmia, and developmental regression are common clinical manifestations.ISs prognosis is primarily determined by its etiology.In recent years, the rapid development of neuroimaging and genetic detection technology has greatly enriched the etiological spectrum of ISs, especially the genetic-related etiology.Likewise, the etiological categorization of ISs has gotten increasingly specific in response to clinical demands.Despite these advances, the etiology of ISs remains complicated and variable, with around one-third of children having unidentified causes.Consequently, more detection methods and studies are still needed to identify other potential etiologies.The etiologic categorization of ISs will be evaluated in this article.

NEXMIF mutations in intellectual disability and epilepsy: A report of 2 cases and literature review / 中南大学学报(医学版)

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.

Phenotype and genotype characteristics of infantile spasm related to UBA5 gene mutation / 中华实用儿科临床杂志

Objective:To analyze the clinical phenotype and genotype characteristics of infantile spasm (IS) associated with UBA5 gene mutation. Methods:Four cases of IS caused by UBA5 gene variation diagnosed at the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were retrospectively analyzed.The clinical manifestations, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), treatment, and follow-up results were summarized. Results:In this study, 4 cases (3 males and 1 female) were clinically diagnosed with IS and carried complex heterozygous variation of UBA5 gene.Genetic analysis confirmed that a total of 6 different mutation sites were found, five of which were unreported.All the 4 cases presented with epileptic spasms at the age of 1 d to 8 months after birth, and 2 cases had focal seizures during the course of disease.The EEG of 4 cases showed hypsarrhythmia and cluster or isolated epileptic spasms were detected.Of the 3 patients who had brain MRI results, 2 cases showed nonspecific abnormalities and 1 case was normal.All the 4 patients had developmental delayed before seizure onset, and regressed to varying degrees and made slow progress after onset.One case had microcephaly, and 3 cases had hypertonia.At the last follow-up, the age of the 4 patients ranged from 7 months to 6 years and 4 months.All 4 patients were treated with multiple antiepileptic drugs, but none of them were under control. Conclusions:Children with IS associated with UBA5 gene variation have an early onset age, often accompanied by developmental delayed, microcephaly, dystonia, and refractory seizures.

Clinical and basic research progress of adrenocorticotropic hormone in treatment of infantile spasm / 中华神经医学杂志

Infantile spasm (IS) is a common epileptic encephalopathy in infancy, characterized by typical epileptic spasm, developmental delay and hypsarrhythmia on interictal electroencephalogram (EEG). Adrenocorticotropic hormone (ACTH) is the first-line treatment medicine for IS. Although ACTH has shown good response to IS and has been widely used, the regime is not identical and the mechanism is still unclear. This paper focuses on the clinical application of ACTH for IS and the anticonvulsant mechanisms of ACTH, in order to provide clinical and theoretical basis for ACTH application.

Tuberous sclerosis in a child

Tuberous Sclerosis (TS) is the most common single gene disorder in children. It has an incidence of 1 in 5800 live births. It is an autosomal dominant genetic multisystemic disease characterized by hamartic development of many organs most notably the brain, heart, kidney, lungs and skin. It results from mutation of TSC1 and TSC2 gene coding for hamartin and tuberin respectively. Most of the newborns are asymptomatic. In infancy, seizures are the most common symptoms with a high incidence of infantile spasm while children between 2- 10 years neurological symptoms are most frequent with epilepsy, mental retardation and autism. Authors report a 4-year-old male child born of grade 3 consanguineous marriage presented with seizures in form of Infantile Spasm and Skin Lesions.

Boonsta-Bosch-Schaff optic atrophy syndrome with infantile spasm: A case and literatures review / 解放军医学杂志

Objective To report a case of Boonsta-Bosch-Schaff optic atrophy syndrome (BBSOAS) with infantile spasm, its clinical features as well as diagnosis and treatment process, and review the relevant literature. Methods Retrospectively analyze the clinical data of a case of BBSOAS with infant spasm patient in the First Medical Center of PLA General Hospital, retrieve the databanks of online human Mendelian genetic database (OMIM), PubMed, CNKI and Wanfang Medical Online, explore the clinical characteristic of BBSOAS with infant spasm patients, the relationship between the phenotype - genotype, and the therapeutic effect. Results The patient was a 9-month-old boy admitted to hospital due to "intermittent convulsions for 4 months". The growth and development of the child delayed, gaze following was poor; fundus examination showed pale optic disc (atrophy, small optic disc), spasm attack, and electroencephalogram indicated hypsarrhythmia. Genetic test found de novo missense mutation in NR2F1 gene c.383G>A (p.YS128tyr), so diagnosed as BBSOAS and Infantile spasms. The spasticity was not controlled and hypsarrhythmia was still existed in electroencephalogram after adrerrmrticotropic hormone (ACTH) and a variety of antiepileptic drugs were administered. Fever occurred 2 weeks after out of hospital oral perampanel, spasms was completely controlled after the febrile retrograde. A total of 9 English references were obtained by searching multiple databases and manual screening, and a total of 46 cases of BBSOAS were found, among which 9 cases were complicated with infantile spasms. All the amino acid changes caused by NR2F1 gene mutation were located in DNA-binding domain, and optic nerve atrophy or/and hypoplasia were observed. Conclusions The new missense mutation of NR2F1 gene c.383G>A that caused BBSOAS and infantile spasm is no literature report before. In case of optic atrophy or hypoplasia associated with spasm in infants and young children, the doctor should consider the possibility of BBSOAS, and do the genetic examination if necessary. Perampanel may be a potential drug for spasm control in such children.

A case report of Kabuki syndrome with infantile spasm and literature review / 解放军医学杂志

Objective Through literature review to retrospectively study the clinical characteristics, treatment and prognosis of Kabuki syndrome with infantile spasm. Methods The clinical data of a case of Kabuki syndrome with infantile spasm hospitalized at the first medical center of Chinese PLA General Hospital in August 2019 were retrospectively analyzed, search on PubMed, CNKI, Wanfang Medical Online and online Mendelian Inheritance in Man (OMIM), to summarize the clinical data of Kabuki syndrome with infantile spasm and to explore its relationship with genotypes. Results A boy, 1 year and 7 months old, was admitted for "growth lag, intermittent convulsions for more than 1 year and 1 month". His growth and development were generally backward, had microcephaly, short stature and spasms, magnetic resonance imaging of brain showed normal, the thyroid hormone and growth hormone levels were normal, genetic analysis revealed a denovo frameshift mutation in KDM6A gene (c.2170-c.2171 delAT, p.I724Ifs∗5), electroencephagram showed hypsarrhuthmia, with a series of convulsions, diagnosed as "infantile spasm; Kabuki syndrome", after treating with ACTH, the spasms was completely controlled, multiple reexamination of EEG significantly improved. A total of 16 English literatures and 1 Chinese literature were obtained. There were 48 children had been diagnosed as Kabuki syndrome with epilepsy, including 6 children as Kabuki syndrome and infantile spasm. Among the above 6 cases, only 2 genetic test results were reported, 1 was missense mutation of KMT2D gene (c.96c >G, p.apsp32glu), and 1 was frameshift mutation of KDM6A gene (c.2515_2518del, p.apsn839valfs). Conclusion The new frameshift mutation of KDM6A gene (c.2170-c.2171delAT) in this child could lead to infantile spasm of Kabuki syndrome. Kabuki syndrome could be associated with infantile spasms. If spasm occurs and accompanied by a special face, Kabuki syndrome needs to be considered, gene sequencing should be performed if necessary, early treatment can completely control infantile spasms in all children with Kabuki syndrome, the abnormal of EEG could back to normal, will have a favorable prognosis.

Progress of genotypes and phenotypes of infantile spasms / 国际儿科学杂志

Infantile spasm is a common type of early epileptic encephalopathy.It is typically featured with the triad of infantile spasms,hypsarrhythmia electroencephalogram and developmental retardation.The causes of infantile spasms include symptomatic,cryptogenic,and unknown factors.With the development of gene diagnosis technology,the number of early epileptic encephalopathy caused by single gene abnormality is increasing gradually.Meanwhile,different genes may present as same phenotype,and vice versa.It provides strong evidence for gene diagnosis and related treatment of the disease.This paper is to summarize the clinical phenotype of infant spasms related ARX,CDKL5,STXBP1,SCN2A,KCNQ2 and TSC gene mutations on the basis of collecting related literature review,which helps to achieve early identification of specific mutations and more specific selection of antiepileptic drugs.

Animal models of infantile spasms / 国际儿科学杂志

Infantile spasms(IS),an age-dependent epileptic encephalopathy seen in infancy,is characterized by unique electro-clinical features and pharmacological reactions.Most conventional antiepileptic drugs are ineffective for IS.Hormonal treatment(including adrenocorticotropic hormone ACTH,and oral steroids)and vigabatrin(VGB) now widely used as first-line treatments for IS,have certain effects on IS,but the effect of these two options on long-term outcomes has not been established.The etiology of IS is variable.It is unclear that how a wide variety of conditions result a common phenotype.Ideal animal models can help to understand pathogenesis of disease and explore new therapies to improve the ultimate outcome.This review summarizes the research status of animal models of IS.

Hippocampal corticotropin releasing hormone mRNA expression and neuroprotective mechanism of adrenocorticotropic hormore in immature rats after N-methyl-D-aspartate induced spasm seizures / 中华神经医学杂志

Objective To study the hippocampal corticotropin releasing hormone (CRH) mRNA expression and neuroprotective mechanism of adrenocorticotropic hormore (ACTH) in immature rats after N-methyl-D-aspartate (NMDA)-induced spasm seizures.Methods Sixty 10-day-old Wistar rats were randomly divided into blank control group,NMDA-induced seizure group and ACTH treatment group (n=20).Rats in the blank control group did not give any treatment;rat models of infantile spasm in the NMDA-induced seizure group and ACTH treatment group were induced by intraperitoneal injection of NMDA (7 mg/kg) for a consecutive 7 d;3 h after NMDA injection,intraperitoneal injection of ACTH 0.5 mg/(kg· d) was performed in the rats of ACTH treatment group,and NMDA-induced seizure group was given an equal volume of saline.By in situ hybridization (ISH),the mean optical density of CRH mRNA-positive neurons in the hippocampus was measured.Results In the ACTH treatment group,the latencies of epileptic seizures one week after treatment were significantly prolonged as compared with those before treatment,and the scores of epileptic seizures one week after treatment were significantly decreased as compared with those before treatment (P＜0.05);the latencies of epileptic seizures were significantly prolonged and the scores of epileptic seizures were significantly decreased in the ACTH treatment group as compared with those in the NMDA-induced seizure group (P＜0.05).The CRH mRNA expression in NMDA-induced seizure group was significantly increased as compared with that in the blank control group (P＜0.05),and the CRH mRNA expression in the ACTH treatment group was significantly decreased as compared with that in the NMDA-induced seizure group (P＜0.05).Conclusion Systemic ACTH has neuroprotective effect via down-regulating the hippocampal CRH mRNA expression.

The efficacy of prednisone in the treatment of infantile spasm and HPA axis mechanism analysis / 国际儿科学杂志

Objective By studying the changes of the seizures of infantile spasm(IS)、EEG and HPA axis function before and after the treatment of prednisone,to explore the efficacy of prednisone in treating infan-tile spasm,the role of HPA axis in the pathogenesis of IS,and elucidate the HPA axis mechanism of prednisone in controling seizure.Methods A total of 30 patients with IS (IS group) and 30 cases of healthy infants and young children (control group) were recruited.Number of seizures、EEG、HPA axis function was detected be-fore and after the treatment of prednisone in patients with infantile spasm.Serum cortisol,ACTH were deter-mined by the chemiluminescence analysis,serum CRH was measured by enzyme-linked immunosorbent assay. Results serum CRH levels of IS group was significantly higher than normal control group(P<0.05).Serum cortisol,ACTH in IS group were no evidently different compared with control group (P>0.05).The average number of daily ictal clusters and the average daily total seizure number positively correlated with CRH respec-tively.After the application of the prednisolone,seizure of 19 cases of the IS were controlled,11 cases were not controlled,18 cases of hyperarrhythmia were completely remited and 12 cases of hyperarrhythmia were not com-pletely remited.The average number of daily ictal clusters and The average daily total seizure number after treat-ment were significantly lower than before treatment(P<0.05);DQ after treatment was higher than DQ before treatment(P<0.05);The pathogenesis was the main influencing factor of the prednisone treatment effect,the length of the disease,the worse the treatment(P<0.05).CRH、cortisol、ACTH after treatment were significantly lower than before treatment(P<0.05).Conclusion Prednisone can effectively control the onset of infantile spasms,and early treatment is better.IS patient has HPA axis dysfunction,and prednisone can regulate HPA axis dysfunction to control spasm.

Comparison of efficacy of adrenocorticotrophic hormone and methylprednisolone on rat models of infantile spasm / 中华实用儿科临床杂志

Objective To compare the efficacy of adrenocorticotrophic hormone (ACTH) and methylprednisolone on the rat models of infantile spasms (IS).Methods The SD rats on postnatal 10 day (P10) were divided into blank group (n =18),control group (n =18) and model group (n =110) according to the random number table method.The rats of model group were prepared by adopting prenatal stress exposure and N-methyl-D aspartate (NMDA) injection.In the model group,after inducing epileptic seizures,the rats were divided into different groups (18 rats in each group) according to the random number table method as following:model group Ⅰ (subcutaneous injection ofACTH,50 IU/kg,at P10:14:00,21:00;P11,P12:7:00,14:00,21:00;P13:7:00),model group Ⅱ (subcutaneous injection of 9 g/L saline),model group Ⅲ (intraperitoneal injection of methylprednisolone,60 mg/kg,at P11,P12,P13:9:00,once per day),model group Ⅳ (intraperitoneal injection of 9 g/L saline) and model group Ⅴ (positive control group,with no drug or saline injection).Three days later,epilepsy was induced again,and the rats of model group were intraperitoneally injected with NMDA (12 mg/kg) at P13 (10:00).The rats of control group were injected intraperitoneally with same volume of 9 g/L saline,but the rats of blank group were not treated.Behaviors of rats with epilepsy seizures were observed and epilepsy scores were given.The expression of corticotropin-releasing hormone (CRH) in the hypothalamus of each group was detected by using immunohistochemistry and fluorescence quantitative polymerase chain reaction.The learning and memorizing capacity of the rats were measured by Y-maze experiment.Results There was no death in the model group after the onset of seizure.In the model group Ⅰ,13 cases were attacked(72.22％),and 14 cases were attacked in the model group Ⅲ (78.78％).The level of attack was decreased.The buckling state was not observed in model group and Ⅲ,but the latency period of epilepsy was prolonged and the epilepsy scores were significantly decreased.There were no significant differences of onset latency [(2 369.38 ± 628.70) s vs.(1 922.93 ± 462.36) s] and epilepsy score [(2.15 ± 1.14) scores vs.(2.07 ± 0.83) scores] between the 2 groups (all P ＞ 0.005).The rats of model group Ⅱ,Ⅳ,Ⅴ were all attacked completely and presented buckling state.There was no onset or death in blank group and control group.The number of CRH positive cells and CRH mRNA relative expression of each model group were higher than those in the blank group and control group.The number of CRH positive cells and CRH mRNA expression of model group Ⅰ and Ⅲ were lower than those in model group Ⅱ,Ⅳand Ⅴ,and the differences were significant (all P ＜ 0.002 4).There was no significant difference in the number of CRH-positive cells(39.12 ± 5.98 vs.41.48 ± 7.61) and CRH mRNA relative expression (1.92 ± 0.16 vs.2.06 ± 0.39) between model group Ⅰ and Ⅲ (all P ＞ 0.002 4).No significant difference was found between blank group and control group,or among model group Ⅱ,Ⅳ and Ⅴ (all P ＞ 0.002 4).There were no significant differences in the learning capacity among all groups (F =2.196,P ＞ 0.002 4).The correct response rate after 24 hours of the model group was lower than the blank group and control group,and ACTH and methylprednisolone pretreatment did not influence the memorizing capacity (P ＞ 0.002 4).Conclusion The effect of pretreatment of ACTH is similar to that of methylprednisolone in the rat model of IS.

Efficacy and retention rate of ketogenic-diet treatment in infantile spasm / 中华实用儿科临床杂志

Objective To explore the effectiveness and compliance of ketogenic-diet(KD) treatment for infantile spasm(IS).Methods Ninety-eight IS patients who were treated with KD in Wuhan Children's Hospital from March 2009 to June 2015 were analyzed by using retrospective case-control study,the patients were divided into 4 groups:newly diagnosed IS patients group (group A,including 24 patients),one antiepileptic drug (AEDs) failure IS patients (group B,including 28 patients),two and more AEDs failure IS patients (group C,including 29 patients),and two or more AEDs combined with ACTH failure IS patients(group D,including 17 patients).The spasm-free andretention rates after 3,6 and 12 months KD treatment were compared among these groups.Results Overall retention rate was 80.6％ (79/98 cases),69.4％ (68/98 cases),and 42.9％ (42/98 cases)at 3,6,12 months,respectively.The 3-month retention rate in group A,B,C and D was 83.3 ％ (20/24 cases),78.6％ (22/28 cases),82.7％ (24/29 cases) and 76.4％ (13/17 cases) respectively,and there was no significant difference among these groups (P ＞ 0.05).The 6-month retention rates in each group was 75.0％ (18/24 cases),67.9％ (19/28 cases),68.8％ (20/29 cases) and 65.0％ (11/17 cases) in sequence,and there was also no significant difference among these groups(P ＞0.05).The 12-month retention rate was 54.2％ (13/24 cases),21.4％ (6/28 cases),48.3％ (14/29 cases) and 52.9％ (9/17 cases) in group A,B,C and D in sequence,the 12-month retention rate of group B was significantly lower than that of other 3 groups,and the differences were statistically significant(x2 =5.973,4.508,4.727,all P ＜ 0.05),and there was no significant difference among the A,C,D groups (all P ＞ 0.05).The spasm-free rate at 3,6,12 months of KD treatment was 19.4％ (19/98 cases),20.4％ (20/98 cases),30.6％ (30/98 cases).The 3-month spasm-free rate in A,B,C,D groups were as follow:41.7％ (10/24 cases),14.3％ (4/28 cases),10.3％ (3/29 cases),11.8％ (2/17 cases),respectively.The 3-month spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant (x2 =10.238,9.219,6.697,all P ＜ 0.05),but there was no significant difference among the B,C,D groups (all P ＞ 0.05).The 6-month spasm-free rates were 41.7％ (10/24 cases),14.3％ (4/28 cases),13.8％ (4/29 cases),and 11.8％ (2/17 cases) in group A,B,C and D in order,and the spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant(x2 =4.924,5.249,4.298,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).The 12-month spasm-free rates were 54.2％ (13/24 cases),21.4％ (6/28 cases),24.1％ (7/29 cases),and 23.5 ％ (4/17 cases) in group A,B,C and D,and the spasm-free rate in group A was significantly higher than that in other 3 groups,and the differences were statistically significant(x2 =8.354,7.923,4.364,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).Conclusions The spasm-free rate of KD therapy for newly-diagnosed IS is higher than that of IS patients whose drug-therapy failed.KD therapy may be the top priority for IS patients and part of those patients whose drug-therapy failed can still get seizure-free with KD diet.

Glucose transport 1 deficiency presenting as infantile spasms with a mutation identified in exon 9 of SLC2A1 / 소아과

Glucose transport 1 (GLUT-1) deficiency is a rare syndrome caused by mutations in the glucose transporter 1 gene (SLC2A1) and is characterized by early-onset intractable epilepsy, delayed development, and movement disorder. De novo mutations and several hot spots in N34, G91, R126, R153, and R333 of exons 2, 3, 4, and 8 of SLC2A1 are associated with this condition. Seizures, one of the main clinical features of GLUT-1 deficiency, usually develop during infancy. Most patients experience brief and subtle myoclonic jerk and focal seizures that evolve into a mixture of different types of seizures, such as generalized tonic-clonic, absence, myoclonic, and complex partial seizures. Here, we describe the case of a patient with GLUT-1 deficiency who developed infantile spasms and showed delayed development at 6 months of age. She had intractable epilepsy despite receiving aggressive antiepileptic drug therapy, and underwent a metabolic workup. Cerebrospinal fluid (CSF) examination showed CSF-glucose-to-blood-glucose ratio of 0.38, with a normal lactate level. Bidirectional sequencing of SLC2A1 identified a missense mutation (c.1198C>T) at codon 400 (p.Arg400Cys) of exon 9.

Effect of N-methyl-D-aspartate-induced infantile spasms on serum corticosterone and adrenocorticotropic hormone levels and hippocampal CRHmRNA expression in young rats / 中华神经医学杂志

Objective To study the effect ofN-methyl-D-aspartate (NMDA)-induced seizures on corticosterone and adrenocorticotropic hormone (ACTH) levels and hippocampal CRHmRNA expression in young rats.Methods Wistar rats at P11 were used in our study and randomly divided into NMDA-induced seizure group (n=20) and control group (n=20); P11 rats of NMDA-induced seizure group received intraperitoneal injection of 7 mg/kg NMDA; normal saline was given to the control group;three h after that,the behavioristics changes were observed,and epilepsy rating was performed.And then,these rats were sacrificed; corticosterone and ACTH levels were determined using radio immunoassay;oligonucleotide CRH mRNA probe was labeled with in situ hybridization.Results The levels of corticosterone and ACTH in the control group ([7.95±0.92] ng/mL and [64.17±6.15] pg/mL) were obviously higher than those in the NMDA-induced seizure group ([13.34 ±2.18] ng/mL and [115.9 ± 16.8] pg/mL),with significant differences (t=10.198,P=0.000; t=12.91,P=0.000).In situ hybridization of CRH mRNA showed that the rate of CRH mRNA-positive cells in the hippocampus of control group was 15％ (3/20),which was significantly lower than that in the NMDA-induced seizure group (60％; x2=8.640,P=0.003).Conclusion serum corticosterone,ACTH and hippocampal CRH mRNA levels in NMDA-induced seizure rats are significantly increased,indicating that pituitary-adrenal axis is activatedby NMDA-induced seizures in young rats.

Estrategia de evaluación genética en el Síndrome West / A strategy of genetic assessment in West’s syndrome

Introducción: La epilepsia ocupa el segundo lugar entre las enfermedades neurológicas de la infancia y produce afectaciones en las esferas afectiva, cognitiva y social de quienes la padecen, así como en su contexto familiar. Objetivo: diseñar una estrategia para la evaluación genética del Síndrome West. Material y método: se realizó un estudio descriptivo, transversal en pacientes con diagnóstico de Síndrome West atendidos en el Centro Provincial de Genética Médica de Pinar del Río desde el primero de enero del 2010 al 31 de Agosto del 2011. Resultados: predominó el Síndrome West en el sexo masculino, con debut de los síntomas entre 4 y 6 meses. Se obtuvo una alta correspondencia entre el diagnóstico de la enfermedad y la identificación de antecedentes prenatales positivos. La amenaza de aborto, el parto pretérmino y la hipoxia neonatal fueron las causas perinatales más atribuidas al desarrollo de la enfermedad. El examen físico dismorfológico fue positivo en la mayoría de los pacientes y aportó elementos que ofrecieron el diagnóstico en casos sin etiología definida. Las pruebas metabólicas y cromosómicas, resultaron útiles en la identificación etiológica del Síndrome West. Se diseñó una estrategia de evaluación genética para los pacientes con Síndrome West. Conclusiones: la caracterización del Síndrome West según los protocolos de estudio, facilitó el manejo de forma integral, permitió identificar las causas responsables del trastorno y se diseñó la estrategia para la evaluación genética de los niños con esta enfermedad.

Introduction: epilepsy occupies the second place among neurological diseases in childhood and it provokes affectations in the emotional, cognitive and social spheres of epilepsy sufferers, as well as in their familial context. Objective: to design a strategy of genetic assessment in West’s syndrome. Material and method: a descriptive and cross-sectional study was conducted in patients suffering from West’s syndrome attended at Provincial Medical Genetics Center in Pinar del Rio from January 1, 2010 - August 31, 2011. Results: West’s syndrome prevailed in male sex and the onset of symptoms by 4 and 6 months. A high correspondence was found between diagnosis of the disease and the identification of positive prenatal history. Threatened abortion, preterm labor and neonatal hypoxia were the perinatal causes ascribed to the development of the disease. Dysmorphological physical examination was positive in the majority of patients and it provided elements that helped with diagnosis of cases without presenting a definite etiology. Metabolic and chromosomal tests were valuable to perform the etiological identification of West’s syndrome. A strategy to carry out the genetic assessment for West’s syndrome patients was designed. Conclusions: West’s syndrome characterization following the protocols of study eased a comprehensive management which allowed the identification of causes and the design of a strategy to complete the genetic assessment of children suffering from this disease.

Rapamycin in tuberous sclerosis patient with infantile spasm: a case report and literature review / 中华神经医学杂志

Objective To analyze the clinical features of tuberous sclerosis (TS) patient with infantile spasm and investigate its treatment efficacy with rapamycin. Methods The clinical manifestations of a tuberous sclerosis patient with infantile spasm before and after the treatment with rapamycin were retrospectively analyzed; and the related literature was reviewed. Results Dermatological abnormalities were evidcnt in the child and mainly shown as hypomelanotic macules.His neurological abnormalities included infantile spasm and backward psychomotor development.Head MRI and CT had abnormal changes.Treatment with rapamycin 3 months later disclosed improvement in many ways: the convulsion seizure of the patient decreased apparently, and MRI showed decreased subependymal tuber size; meanwhile,the intellectual development of the patient improved obviously,and there was no adverse reaction. Conclusion Rapamycin,enjoying good effect,would be a new and safety method to treat TS patients with infantile spasm.

Refractory seizures with global developmental delay: A rare cause.

Aicardi syndrome is a genetic disorder characterized by the triad of infantile spasm in flexion, callosal agenesis and ocular abnormalities (chorioretinal lacunae, coloboma of optic disc). We report a typical case of Aicardi syndrome with all the classical features.

Long-term outcomes of infantile spasms / 소아과

PURPOSE: The aims of this study were to investigate the long-term outcomes in children with infantile spasms (IS) and to identify the prognostic factors influencing their neurodevelopment. METHODS: We retrospectively evaluated seventy two children over five years old who were treated for IS at Asan Medical Center, Seoul, Korea, between 1994 and 2007. Forty-three children were contacted by telephone or medical follow-up to assess their current neurodevelopmental status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence interval (95% CIs) of risk factors for unfavorable outcomes. RESULTS: The mean follow-up duration for these 43 children was 7.2+/-1.5 years (range, 4.5 to 13.0 years). Of these, 13 (30.2%) had cryptogenic and 30 (69.8%) had symptomatic IS. Eleven (25.6%) children were initially treated with adrenocorticotrophic hormone (ACTH) therapy, with a mean treatment lag of 1.3+/-1.9 months (range; 0.1 to 7.0 months). Eighteen (41.8%) children clinically responded to initial treatment, as shown by EEG response. Overall, 22 (51.2%) children had at least moderate neurodevelopmental disorders and 2 (4.8%) died. In univariate analysis, etiology (symptomatic) and poor electroclinical response to initial treatment were related to long-term unfavorable outcomes. In multivariate analysis, response to primary treatment was the sole significant independent risk factor with a high OR. CONCLUSION: Overall prognosis of children with IS was poor. Electroclinical non-responsiveness to initial treatment was related to unfavorable long-term outcomes, indicating that initial control of seizures may be important in reducing the likelihood of poor neurodevelopment.