Analysis of the efficacy and influencing factors of sodium channel blockers in the treatment of focal epilepsy in infants under 6 months of age / 中华儿科杂志

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.

Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China / 中华医学杂志(英文版)

Background@#Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China.@*Methods@#We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test.@*Results@#We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ2 = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study.@*Conclusions@#The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

Diagnosis of intellectual disability/global developmental delay via genetic analysis in a central region of China / 中华医学杂志(英文版)

BACKGROUND@#Advanced technology has become a valuable tool in etiological studies of intellectual disability/global developmental delay (ID/GDD). The present study investigated the role of genetic analysis to confirm the etiology in ID/GDD patients where the cause of the disease was uncertain in central China.@*METHODS@#We evaluated 1051 ID/GDD children aged 6 months to 18 years from March 2009 to April 2017. Data concerning basic clinical manifestations were collected, and the method of etiology confirmation was recorded. Genome-wide copy number variations (CNVs) detection and high-throughput sequencing of exons in the targeted regions was performed to identify genetically-based etiologies. We compared the incidence of different methods used to confirm ID/GDD etiology among groups with differing degrees of ID/GDD using the Chi-square or Fisher exact probability test.@*RESULTS@#We recruited 1051 children with mild (367, 34.9%), moderate (301, 28.6%), severe (310, 29.5%), and profoundly severe (73, 6.9%) ID/GDD. The main causes of ID/GDD in the children assessed were perinatal factors, such as acquired brain injury, as well as single gene imbalance and chromosomal gene mutation. We identified karyotype and/or CNVs variation in 46/96 (47.9%) of cases in severe ID/GDD patients, which was significantly higher than those with mild and moderate ID/GDD of 34/96 (35.4%) and 15/96 (15.6%), respectively. A total of 331/536 (61.8%) patients with clear etiology have undergone genetic analysis while 262/515 (50.9%) patients with unclear etiology have undergone genetic analysis (χ = 12.645, P < 0.001). Gene structure variation via karyotype analysis and CNV detection increased the proportion of children with confirmed etiology from 51.0% to 56.3%, and second-generation high-throughput sequencing dramatically increased this to 78.9%. Ten novel mutations were detected, recessive mutations in X-linked genes (ATPase copper transporting alpha and bromodomain and WD repeat domain containing 3) and dominant de novo heterozygous mutations in X-linked genes (cyclin-dependent kinase like 5, protocadherin 19, IQ motif and Sec7 domain 2, and methyl-CpG binding protein 2) were reported in the study.@*CONCLUSIONS@#The present study indicates that genetic analysis is an effective method to increase the proportion of confirmed etiology in ID/GDD children and is highly recommended, especially in ID/GDD children with uncertain etiology.

The relationship between nutritional status and cognitive function in Alzheimer's disease / 肠外与肠内营养

Objective:To investigate the relationship between nutritional status and cognitive function in patients with Alzheimer's disease (AD),and to provide rationale for clinicians in nutrition intervention of AD patients.Methods:Sixty cases of elderly AD patients and 50 cases with normal elderly control were enrolled from the neurological department.Nutritional status and cognitive function were assessed using the laboratory parameters,mini nutritional assessment method (short-form Mini-Nutritional fine assessment,MNA-SF) and MMSE (Mini-Mental State,Examination,MMSE) survey.Results:Compared with control group,the AD group had significantly different laboratory index and MNA-SF score (P ＜ 0.05).MNA-SF scores were positively correlated with MMSE scores in patients with AD (r =0.59,P ＜ 0.05).Conclusion:The incidence of malnutrition in AD patients is high,and it is related to their cognitive function.The nutritional knowledge should be strengthened among doctors and nurses treating patients with AD.

Clinical features and genome-wide copy number variation analysis in 60 children with early-onset epileptic encephalopathies of unknown cause / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features of early-onset epileptic encephalopathies (EEEs) of unknown cause, and to identify pathogenic microdeletion/microduplication of EEEs by genome-wide analysis of copy number variations (CNVs).</p><p><b>METHODS</b>The clinical data of 60 children diagnosed with unexplained EEEs between July 2012 and April 2013 were obtained and analyzed. Specimens were collected from the selected children and their parents. Single nucleotide polymorphism array was used to detect genome-wide CNVs, and fluorescence in situ hybridization was performed to verify the results and analyze the source of the parents, further to identify suspected pathogenic CNVs of EEEs.</p><p><b>RESULTS</b>Among the 60 children with unexplained EEEs, 34 were diagnosed with West syndrome, 3 with Ohtahara syndrome, 3 with Dravet syndrome, and 20 with unclassified EEEs. In total, 77% of the patients were associated with moderate to severe mental retardation. Head imaging test implied that 35% of the patients had brain dysplasia or astrophy. Among 54 patients, 17% showed microcephalus. After treatment, 28 patients had clinical seizures under control, 16 out of control, 5 dead, and 1 lost to follow-up. Genome-wide analysis of CNVs showed that 7 pathogenic or suspected pathogenic CNVs were present in 5 patients.</p><p><b>CONCLUSIONS</b>EEEs of unknown cause are associated with high phenotypic heterogeneity and poor prognosis. Genome-wide CNVs analysis can demonstrate pathogenic or suspected pathogenic CNVs. This research expands the gene bank of EEEs and improves the understanding about possible etiology of unexplained EEEs. The results provide a reference for genetic counseling regarding reproduction in the patient's family.</p>

Expression and activity change of angiotensin converting enzyme in the placenta of preeclampsia / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of angiotensin converting enzyme (ACE) in the pathogenesis of preeclampsia.@*METHODS@#A cross-sectional study was conducted with 42 pregnant women in the following categories: 30 cases of preeclampsia (mild preeclampsia, n=15; severe preeclampsia, n=15), and normal pregnancy (control group,n=12). The expression and localization of ACE mRNA in the placenta of the 3 groups were respectively examined by in situ hybridization. Ultraviolet radiation colorimetry was used to detect the activity of ACE in the placenta tissue homogenate and the mothers' serum in the 3 groups.@*RESULTS@#The expression of ACE mRNA was found in the endothelial cells of villus and trophoblasts in the placenta. The positive index of ACE mRNA in the placenta of preeclampsia(3.12+/-0.94) was higher than that in the normal pregnancies(1.65+/-0.67) (P<0.05), and there was significant difference between severe preeclampsia and mild preeclampsia (P<0.05). The levels of ACE activity in the placenta tissue homogenate and the maternal serum of preeclampsia were higher than those in the normal pregnancies (P<0.05), and there was significant difference between severe preeclampsia and mild preeclampsia (P<0.05). The placenta tissue homogenate ACE activity was correlated with ACE activity of the maternal serum (r=0.781,P<0.05).@*CONCLUSION@#The expression and activity of local ACE in the placenta tissue may play an important role in preeclampsia and contribute to the development of preeclampsia.

Effect of noninvasive intranasal delivery of nerve growth factor on pyriform cortex of sarin-poisioned rats / 中华神经科杂志

Objective To study the effect of intranasal(IN)delivery of nerve growth factor(NGF) on pyriform cortex of satin-poisoned rats.Methods Sprague-Dawley rats were treated with satin and atropine sulphate, pralidoxime to establish satin-poisoned rat model.Then NGF or saline was administered via the olfactory pathway.24 hours later, damaged and residual healthy neurons were estimated and quantified on pyriform cortex using hematoxylin-eosin(HE)staining and neuronal nuclei antigen(NeuN) immunohistochemistry.Results A massive quantity of degenerating neurons were seen in the pyriform cortex of rats with intranasal saline.And compared to the normal rats, the number of neurons of rats with intranasal saline was significantly reduced by 39.44% [(404.75?25.17)/mm~2].But the number of neurons in rats with intranasal NGF [(651.94?36.02)/mm~2] didn't change significantly compared to the normal rats.Conclusion Intranasal delivery of NGF, reducing the degenerating neurons on pyriform cortex of satin-exposure rats, is a potential treatment for satin intoxication.