Clinical analysis of developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep: A single tertiary care center experience in China.

PURPOSE: To analyze the electroclinical features of patients with developmental and/or epileptic encephalopathy with spike-and-wave activation in sleep (DEE/EE-SWAS) and study the efficacy of different therapies on seizure control, electroencephalogram (EEG) improvements of electrical status epilepticus during sleep (ESES), and cognition outcomes. METHODS: Patients with DEE/EE-SWAS who underwent at least one follow-up EEG 3 months after therapy were retrospectively enrolled. The demographic and clinical characteristics of the patients were analyzed. Variables that influenced the outcomes were evaluated using logistic regression models. RESULTS: In total, 87 patients (47 males) were included. The median age at ESES recognition was 81.0 months (IQR 64.0, 96.0). Forty-six patients were diagnosed with self-limited focal epilepsies (SeLFEs) before ESES recognition, 24 with developmental and epileptic encephalopathies with spike-and-wave activation in sleep (DEE-SWAS), and 17 with other epilepsies. Steroids, benzodiazepines, and antiseizure medications (ASMs) were the initial treatment options for ESES. Patients with structural etiologies or slow EEG backgrounds at the time of ESES recognition were less likely to respond to treatment than other patients. However, only children with slow EEG backgrounds had lower odds of response in logistic regression models. Children with clinical or EEG response showed improvements in cognition. CONCLUSION: Steroids, benzodiazepines, and ASMs are effective treatments for patients with DEE/EE-SWAS. Children with structural etiologies or slow EEG backgrounds at the time of ESES recognition may have a poor long-term prognosis. The efficacy of seizure reduction and EEG improvement is associated with cognitive improvement.

Effects of partial substitution of chemical fertilizer with organic manure on the activity of enzyme and soil bacterial communities in the mountain red soil.

Introduction: The partial substitution of chemical fertilizer with organic manure takes on a critical significance to enhancing soil quality and boosting sustainable agricultural development. However, rare research has studied the effects of partial substitution of chemical fertilizer with organic manure on soil bacterial community diversity and enzyme activity in maize field in the mountain red soil region of Yunnan. Methods: In this study, four treatments were set up in which chemical fertilizer (the application rates of N, P2O5 and K2O were 240, 75 and 75 kg·ha-1, respectively) was substituted by 10% (M10), 20% (M20), 30% (M30) and 40% (M40) of organic manure with equal nitrogen, as well as two control treatments of single application of chemical fertilizer (M0) and no fertilization (CK). The maize (Zea mays L.) crop was sown as a test crop in May 2018. The effects of partial substitution of chemical fertilizer with organic manure on soil physicochemical properties, soil bacterial community diversity and enzyme activity were studied. Results: The activities of Cellulase (CBH), Invertase (INV) and ß-glucosidase (BG) increased with the increase of organic manure substitution ratio. The activities of ß-1,4-N-acetylglucosaminidase (NAG), Urease (URE), and leucine aminopeptidase (LAP) also had the same trend, but the highest activities were 159.92 mg·g-1·h-1, 66.82 mg·g-1·h-1 and 143.90 mg·g-1·h-1 at 30% substitution ratio. Compared with CK and M0 treatments, Shannon index increased notably by 82.91%-116.74% and 92.42%-128.01%, respectively, at the organic manure substitution ratio ranging from 10% to 40%. Chao1 and ACE index increased significantly at the organic manure substitution ratio ranging from 10% to 30%. Proteobacteria was the dominant phylum in all treatments, the relative abundance of Proteobacteria decreased as the organic manure substitution ratio increased. Redundancy analysis showed that microbial biomass C was the main factor affecting the bacterial community composition under partial replacement of chemical fertilizer treatment, while Actinobacteria was the main factor affecting the enzyme activity. In addition, the maize yield of M30 and M40 treatments was significantly higher than that of CK and M0-M20 treatments, and the yield of M30 treatment was the highest, reaching 7652.89 kg·ha-1. Conclusion: Therefore, the partial substitution of chemical fertilizer with organic manure can improve soil biological characteristics, while increasing bacterial community diversity and soil enzyme activity. Therefore, a thirty percent organic manure substitution was determined as the optimal substitution ratio for maize farmland in the mountain red soil area of Yunnan, China.

Effects of nitrogen fertilizers on the bacterial community diversity and the weathering of purple mudstone in Southwest China.

Introduction: Rock weathering is crucial in the development of soil. Yet the role of bacteria in the fine particle-forming process of purple mudstone is not fully understood, especially under nitrogen fertilization. Methods: In this study, the particles (0.25 mm to 1 mm) of purple mudstone from Penglai Group (J3p) were selected as the test material. Two nitrogen fertilizers, i.e., urea (U) and ammonium bicarbonate (AB), and four application levels (0, 280, 560, and 840 N kg∙ha-1) with 18 replications were designed in an incubation experiment. The weathering indices and bacterial community structure of the purple mudstone particles were investigated after 120 days of incubation. Results: The results showed that the weathering indices of purple mudstone particles in the AB treatment were higher than that in the U treatment at the same fertilization levels and a reducing trend was observed with increasing nitrogen fertilizer levels under the same nitrogen fertilizer application types. The diversities of the bacterial community were extremely significantly altered by nitrogen fertilizer application (p < 0.01). The effect of the nitrogen fertilizer application level on the beta diversity of the bacterial community (R2 = 0.34) was greater than that of the nitrogen fertilizer application type (R2 = 0.20). Through stepwise regression analysis, the positive effects of nitrification of Nitrobacter (Nitrolancea) (R2 = 0.36), the Phosphorous-dissolving bacteria (Massilia) (R2 = 0.12), and N-NO3- (R2 = 0.35) on the weathering indices of J3p purple mudstone particles could be observed. Structural equation modelling indicated that nitrogen fertilizer application level affects the abundance of the dominant species at the genus level (Nitrolancea and Massilia), and key environmental factor (N-NO3-), which in turn accelerated the weathering indices (59%). Discussion and Conclusion: Our findings imply that the enhancements of nitrification of Nitrobacter (Nitrolancea) and of phosphorus solubilization of Phosphorous-dissolving bacteria (Massilia) by nitrogen fertilization are the key factors affecting the weathering indices of J3p purple mudstone particles.

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus.

AIMS: Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics. METHODS: Ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann-Whitney U test corrected by Benjamini-Hochberg and partial least squares discriminant analysis (PLS-DA). RESULTS: The PLS-DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS-DA with R2 Y = 0.992 and Q2 = 0.798). A total of 49 prognosis-related metabolites were identified. Of these metabolites, 20 including glutamyl-glutamine, 3-iodothyronamine, and L-fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl-glutamine and 3-iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis. CONCLUSIONS: This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established.

Acidic condition accelerates cation release from purple rock in Southwestern China.

In spite of the fact that rock weathering performs an essential task in the evolution of the Earth's surface, the quantitative assessment between pH and rates of chemical weathering remain unclear. This study aims to characterize the chemical weathering rate of purple rocks and then develops a model to calculate the release rates of cations (K+, Na+, Ca2+ and Mg2+) under various pH conditions. Two types of purple rock were sampled from the Shaximiao Group (J2s) and Penglaizhen Group (J3p), and a series of laboratory experiments were performed by soaking the purple rocks in solutions with pHs from 2.5 to 7.0, over 24 treatment cycles. The results showed that the release rates of cations apparently increased as the pH decreased. The release of Ca2+ was the dominant process of chemical weathering in J3p under various pH treatments, while K+ and Na+ were remarkably high in J2s (with the exception of the pH 2.5 treatment). Quantitative analysis revealed that the rate of cation release was significantly related to the H+ concentration (p < 0.001) and the air temperature (p < 0.001). The relationship between cation release and acidity was found to be an exponential function. Our results suggested that solution acidity serves as an important driving force for cation release rates from purple rocks and that environmental acidification would enhance rock weathering.

Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis.

Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms. Methods: One hundred and seventeen autistic children and 119 healthy children were recruited from research centers of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA), and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analyzed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis. Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine, and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine, and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine [area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726], creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668), and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism. Conclusions: Urinary amino acid metabolites were significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

LAY ABSTRACT: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.

High genetic burden in 163 Chinese children with status epilepticus.

PURPOSE: This study aimed to investigate the genetic aetiology in Chinese children diagnosed with status epilepticus (SE). METHODS: Next-generation sequencing, copy number variation (CNV) analysis, and other genetic testing methods were conducted for children with SE lacking an identifiable non-genetic aetiology. Furthermore, the phenotype and molecular data of patients with SE were retrospectively analysed. RESULTS: Among children with SE lacking an identifiable non-genetic aetiology, 73 out of 163 children (44.8 %) were found to have causative variants associated with SE including 66 monogenic mutations in 22 genes and 7 CNVs. Based on the American College of Medical Genetics and Genomics scoring system, the monogenic variants included 64 pathogenic/likely pathogenic and 2 uncertain significance variants. SCN1A gene mutations (n = 32) were the most common cause, followed by TSC2 (n = 5), CACNA1A (n = 5), SCN2A (n = 4), SCN9A (n = 2) and DEPDC5 (n = 2) gene mutations. Sixteen mutations were identified in single genes. Furthermore, 51 (77.3 %) monogenic mutations were de novo. Age at SE onset < 1 year (odds ratio [OR] = 2.70, 95 % confidence interval [CI]: 1.25-5.83, p = 0.012) and co-morbidity of intellectual disability (OR = 3.36, 95 %CI: 1.61-6.99, p = 0.001) were independently associated with pathogenic genetic variants. CONCLUSION: This study identified genetic aetiology in 44.8 % of patients with SE, which indicates a high burden of genetic aetiology among children with SE in China. Our findings highlight the importance for genetic testing of children with SE that lacks an identifiable non-genetic aetiology.

The role of Hipk2-p53 pathways in arsenic-induced autistic behaviors: A translational study from rats to humans.

Previous studies have associated the risk of autism spectrum disorder (ASD) with increased exposures to metals and metalloids such as arsenic. In this study, we used an animal-to-human translational strategy to identify key molecular changes that potentially mediated the effects of arsenic exposures on ASD development. In a previously established rat model, we have induced autistic behaviors in rat pups with gestational arsenic exposures (10 and 45 µg/L As2O3 in drinking water). Neuronal apoptosis and the associated epigenetic dysregulations in frontal cortex were assayed to screen potential mediating pathways, which were subsequently validated with qPCR, western blotting, and immunohistochemistry analyses. Furthermore, the identified pathway, along with serum levels of 26 elements including arsenic, were characterized in a case-control study with 21 ASD children and 21 age-matched healthy controls. In animals, we found that arsenic exposures caused difficulties of social interaction and increased stereotypic behaviors in a dose-dependent manner, accompanied by increased neuronal apoptosis and upregulation of Hipk2-p53 pathway in the frontal cortex. In humans, we found that serum levels of Hipk2 and p53 were 24.7 (95%CI: 8.5 to 43.4) % and 23.7 (95%CI: 10.5 to 38.5) % higher in ASD children than in healthy controls. ASD children had significantly higher serum levels of 15 elements, among which arsenic, silicon, strontium, and vanadium were positively associated with both Hipk2 and p53. Results from both the rat arsenic exposure and human case-control studies suggest a likely role of Hipk2-p53 pathway in ASD development induced by exposures to environmental pollutants such as arsenic.

Prevalence of Autism Spectrum Disorder in China: A Nationwide Multi-center Population-based Study Among Children Aged 6 to 12 Years.

This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder (ASD) in Chinese children. We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling. The Modified Chinese Autism Spectrum Rating Scale was used for the screening process. Of the target population of 142,086 children, 88.5% (n = 125,806) participated in the study. A total of 363 children were confirmed as having ASD. The observed ASD prevalence rate was 0.29% (95% CI: 0.26%-0.32%) for the overall population. After adjustment for response rates, the estimated number of ASD cases was 867 in the target population sample, thereby achieving an estimated prevalence of 0.70% (95% CI: 0.64%-0.74%). The prevalence was significantly higher in boys than in girls (0.95%; 95% CI: 0.87%-1.02% versus 0.30%; 95% CI: 0.26%-0.34%; P < 0.001). Of the 363 confirmed ASD cases, 43.3% were newly diagnosed, and most of those (90.4%) were attending regular schools, and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity. Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.

[Autism spectrum disorder-like symptoms in the population with intellectual disability aged 6 to 18 years].

OBJECTIVE: To investigate the incidence of autism spectrum disorder (ASD)-like symptoms in the population with intellectual disability (ID). METHODS: The students with ASD or ID, aged 6-18 years, who studied in a special school in Shanghai from January to June, 2017, as well as the typically developing (TD) population of the same age, who studied in a general school in Shanghai during the same period, were enrolled. Social Responsiveness Scale (SRS) was completed by their parents or other guardians, and the ASD-like symptoms were evaluated. RESULTS: A total of 69 subjects with ASD, 74 subjects with ID and 177 TD subjects were enrolled. The ID group had a significantly higher SRS-positive rate than the TD group (47.3% vs 1.7%; P<0.001) and a significantly lower SRS-positive rate than the ASD group (47.3% vs 87.0%; P<0.001). The total score of SRS was 114±26 in the ASD group, 80±24 in the ID group and 38±19 in the TD group. The ID group had a significantly higher total score of SRS than the TD group (P<0.05), and the score on the subscale of social cognition showed the most significant difference between the two groups (Cohen's d=2.00). There were no significant differences in the total score of SRS and the scores on each subscale of SRS between the mild-to-moderate ID and severe-to-extremely severe ID groups (P>0.05), and there was no significant correlation between SRS score and IQ (P>0.05). CONCLUSIONS: The ID population aged 6-18 years has more ASD-like symptoms than the general population, and ASD screening and intervention should be performed for the ID population as early as possible.

The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.

There is still no comprehensive description of the general population regarding clinical features and genetic etiology for co-occurring epilepsy and autism spectrum disorder (ASD) in Chinese children. This study was a retrospective study of children diagnosed with epilepsy and ASD from January 1st, 2015, to May 1st, 2018, at the Children's Hospital of Fudan University. A total of 117 patients met the inclusion criteria, and 103 subjects were eligible. Among them, 88 underwent genetic testing, and 47 children (53.4%) were identified as having pathogenic or likely pathogenic variants: 39 had single gene mutations (83.0%, 39/47), and eight had copy number variants (17.0%, 8/47), with SCN1A (14.9%, 7/47) and MECP2 (10.6%, 5/47) gene mutations being the most common. Mutations in other genes encoding voltage-gated ion channels including SCN2A, CACNA1A, CACNA1H, CACNA1D, and KCNQ2 were also common, but the number of individual cases for each gene was small. Epilepsy syndrome and epilepsy-associated syndrome were more common (P = 0.014), and higher rates of poly-therapy (P = 0.01) were used in the positive genetic test group than in the negative group. There were no statistically significant differences in drug-refractory epilepsy, ASD severity, or intellectual disability between the positive genetic test group and the negative genetic group. These data strongly indicate the need for ASD screening in children with epilepsy with voltage-gated ion channel gene variants for better diagnosis and early intervention.

Reliability and validity of the translated Chinese version of Autism Spectrum Rating Scale (2-5 years).

BACKGROUND: Early autism screening is of great value, but there is lack of a screening tool of early age (2-5 years) in China. The Autism Spectrum Rating Scale (ASRS, 2-5 years) is a newly developed autism screening tool in the USA. This study aimed to evaluate the reliability and validity of the translated Chinese version of ASRS (C_ASRS) in Chinese children population before its application in China for early autism screening. METHODS: Caregivers of general children aged 2-5 years from 17 kindergartens and autism spectrum disorder (ASD) cases from five special education schools in five cities were recruited to complete the C_ASRS. 1910 valid questionnaires from kindergarteners and 192 from ASD cases were included for analyses. RESULTS: The item reliability (Cronbach's alpha) was more than 0.80 in the screening scale and DSM-5 scale, and 0.51-0.81 in the treatment scale. ASD cases scored higher on total score and most subscales compared to the kindergarteners (Cohen's d ranging from 1.34 to 3.37). C_ASRS showed good discriminatory validity with an area under the receiver operating characteristic curve of 0.850 (95% confidence interval: 0.819-0.881). The cutoff ≥ 60 achieved sensitivity of 65.63% and specificity of 85.63% in discriminating autism children from the general population. CONCLUSION: The results indicate that C_ASRS (2-5 years) could be used as an early level-2 screening tool for autism screening in China and should be further revised for level-1 screening.

Cross-Cultural Revision and Psychometric Properties of the Chinese Version of the Autism Spectrum Rating Scale (2-5 Years).

Background: No sufficient biomarkers are available for early identification of autism in the general population. Currently, the diagnosis of ASD depends on behavioral assessments. A useful screening tool can help to detect early autistic symptoms and provide children an early opportunity for ASD-related interventions. This research aimed to assess cross-cultural adaptation and psychometric properties of the autism spectrum rating scale (ASRS) under the Chinese cultural environment. Methods: Participants were recruited from 17 kindergartens and 5 special education schools across five cities (Shanghai, Guangzhou, Changsha, Chengdu, and Harbin) in China. A total of 2,181 kindergarten children and 207 ASD cases participated in this study. Mplus 7.03 was utilized to conduct exploratory factor analysis, followed by adaptive modifications to construct the revised Chinese version of the ASRS (RC_ASRS). Results: The result showed that 62 items comprised a two-factor structure; Factor 1 (social communication, SC) included 21 items, and Factor 2 (unusual behavior, UB) included 41 items. Cronbach's alpha ranged from 0.87 to 0.91 within the RC_ASRS. The total score and the SC and UB scores were significantly higher in ASD cases than in kindergarten samples (Cohen's d ranged from 0.82 to 2.72). The total RC_ASRS score showed an area under the curve (AUC) of 0.95 (95% CI: 0.93-0.97). With a total score cut-off ≥ 60, the RC_ASRS is an excellent tool to identify ASD cases from Chinese kindergarten children (sensitivity = 88.6%, specificity = 84.5%). Conclusions: The RC_ASRS has excellent psychometric properties and is a reliable, useful tool for early ASD screening among Chinese children.

Performance of the Autism Spectrum Rating Scale and Social Responsiveness Scale in Identifying Autism Spectrum Disorder Among Cases of Intellectual Disability.

The Autism Spectrum Rating Scale (ASRS) and the Social Responsiveness Scale (SRS) have been widely used for screening autism spectrum disorder (ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability (ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6-18 years from special education schools, and 402 typically developing (TD) children in the same age span from a community-based population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales (P < 0.05) but higher than TD children (P < 0.05). Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS (area under the curve (AUC) = 0.709, sensitivity = 77.0%, specificity = 52.1%, positive predictive value (PPV) = 82.2%) and the SRS (AUC = 0.742, sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%). The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree.

Assessment of the neuropsychiatric comorbidities in Chinese children with epilepsy using the MINI-KID tool.

This study aimed to assess neuropsychiatric comorbidities and analyze risk factors in Chinese children with epilepsy. Children with epilepsy aged between 6 and 16 years from the Children's Hospital of Fudan University were included. Children with asthma and typically developing children were matched for age and gender, and served as control groups. Neuropsychiatric disorders were assessed by interviewing the parents or guardians using the Mini International Neuropsychiatric Interview for children (MINI-KID) (parent version). Basic information and clinical data were also collected using an author designed questionnaire. Multiple logistic regression analysis was done to identify the risk factors associated with neuropsychiatric comorbidities. In this study, 140 children with epilepsy, 70 children with asthma and 70 typically developing children were recruited. Neuropsychiatric disorders were significantly more common in children with epilepsy (41.4%) as compared with the asthma group (15.7%) and the control group (10.0%). Of the 58 children with epilepsy who had neuropsychiatric comorbidities, only 29.3% had been diagnosed before our study. Multivariate analysis revealed that a younger age at seizure onset (OR=0.877, 95%CI: 0.773∼0.996), seizures occurring more than once monthly during the past year (OR=3.526, 95%CI: 1.177∼10.562), polytherapy (OR=2.632, 95%Cl: 1.066∼6.501) were all significantly associated with neuropsychiatric comorbidities in children with epilepsy. In conclusion, children with epilepsy are more likely to have neuropsychiatric comorbidities, and up to 70% of them were undiagnosed. Early screening, diagnosis and treatment of neuropsychiatric comorbidities in children with epilepsy may improve the long-term prognosis.

Motor patterns of the small intestine explained by phase-amplitude coupling of two pacemaker activities: the critical importance of propagation velocity.

Phase-amplitude coupling of two pacemaker activities of the small intestine, the omnipresent slow wave activity generated by interstitial cells of Cajal of the myenteric plexus (ICC-MP) and the stimulus-dependent rhythmic transient depolarizations generated by ICC of the deep muscular plexus (ICC-DMP), was recently hypothesized to underlie the orchestration of the segmentation motor pattern. The aim of the present study was to increase our understanding of phase-amplitude coupling through modeling. In particular the importance of propagation velocity of the ICC-DMP component was investigated. The outcome of the modeling was compared with motor patterns recorded from the rat or mouse intestine from which propagation velocities within the different patterns were measured. The results show that the classical segmentation motor pattern occurs when the ICC-DMP component has a low propagation velocity (<0.05 cm/s). When the ICC-DMP component has a propagation velocity in the same order of magnitude as that of the slow wave activity (∼1 cm/s), cluster type propulsive activity occurs which is in fact the dominant propulsive activity of the intestine. Hence, the only difference between the generation of propagating cluster contractions and the Cannon-type segmentation motor pattern is the propagation velocity of the low-frequency component, the rhythmic transient depolarizations originating from the ICC-DMP. Importantly, the proposed mechanism explains why both motor patterns have distinct rhythmic waxing and waning of the amplitude of contractions. The hypothesis is brought forward that the velocity is modulated by neural regulation of gap junction conductance within the ICC-DMP network.