Exploring Infantile Epileptic Spasm Syndrome: A Proteomic Analysis of Plasma Using the Data-Independent Acquisition Approach.

This study aimed to identify characteristic proteins in infantile epileptic spasm syndrome (IESS) patients' plasma, offering insights into potential early diagnostic biomarkers and its underlying causes. Plasma samples were gathered from 60 patients with IESS and 40 healthy controls. Data-independent acquisition proteomic analysis was utilized to identify differentially expressed proteins (DEPs). These DEPs underwent functional annotation through Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Gene set enrichment analysis (GSEA) was employed for both GO (GSEA-GO) and KEGG (GSEA-KEGG) analyses to examine the gene expression profiles. Receiver operating characteristic (ROC) curves assessed biomarkers' discriminatory capacity. A total of 124 DEPs were identified in IESS patients' plasma, mainly linked to pathways, encompassing chemokines, cytokines, and oxidative detoxification. GSEA-GO and GSEA-KEGG analyses indicated significant enrichment of genes associated with cell migration, focal adhesion, and phagosome pathways. ROC curve analysis demonstrated that the combination of PRSS1 and ACTB, PRSS3, ACTB, and PRSS1 alone exhibited AUC values exceeding 0.7. This study elucidated the significant contribution of cytokines, chemokines, oxidative detoxification, and phagosomes to the IESS pathogenesis. The combination of PRSS1 and ACTB holds promise as biomarkers for the early diagnosis of IESS.

ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation.

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

Association of FAT1 with focal epilepsy and correlation between seizure relapse and gene expression stage.

PURPOSE: The FAT1 gene encodes FAT atypical cadherin 1, which is essential for foetal development, including brain development. This study aimed to investigate the relationship between FAT1 variants and epilepsy. METHODS: Trio-based whole-exome sequencing was performed on a cohort of 313 patients with epilepsy. Additional cases with FAT1 variants were collected from the China Epilepsy Gene V.1.0 Matching Platform. RESULTS: Four pairs of compound heterozygous missense FAT1 variants were identified in four unrelated patients with partial (focal) epilepsy and/or febrile seizures, but without intellectual disability/developmental abnormalities. These variants presented no/very low frequencies in the gnomAD database, and the aggregate frequencies in this cohort were significantly higher than those in controls. Two additional compound heterozygous missense variants were identified in two unrelated cases using the gene-matching platform. All patients experienced infrequent (yearly/monthly) complex partial seizures or secondary generalised tonic-clonic seizures. They responded well toantiseizure medication, but seizures relapsed in three cases when antiseizure medication were decreased or withdrawn after being seizure-free for three to six years, which correlated with the expression stage of FAT1. Genotype-phenotype analysis showed that epilepsy-associated FAT1 variants were missense, whereas non-epilepsy-associated variants were mainly truncated. The relationship between FAT1 and epilepsy was evaluated to be "Strong" by the Clinical Validity Framework of ClinGen. CONCLUSIONS: FAT1 is a potential causative gene of partial epilepsy and febrile seizures. Gene expression stage was suggested to be one of the considerations in determining the duration ofantiseizure medication. Genotype-phenotype correlation helps to explain the mechanisms underlying phenotypic variation.

Effect of different amounts of bamboo charcoal on properties of biodegradable bamboo charcoal/polylactic acid composites.

Biodegradable composites were prepared from polylactic acid (PLA) and bamboo charcoal (BC) by melt blending and hot pressing. The effects of BC addition on the mechanical properties, water absorption, DMA, TGA, DSC, and CONE of BC/PLA composites were investigated. The microscopic morphology of the composites was analyzed by SEM. The results showed that for BC addition of 40 wt%, the mechanical strength, thermal properties, and flame retardant properties of the composites were improved compared with those of PLA, with a 2.24 % increase in flexural strength and a 1535 % increase (500 °C) in TG mass retention rate. The crystallinity increased by 129.66 %, the peak loss factor decreased by 31.15 %, the time required for combustion was delayed by 168 s, the peak heat release rate decreased by 29.40 %, the carbon residue rate detected by cone calorimetry increased by 48.50 %, and the peak mass loss rate decreased by 48.82 %. The addition of BC enhanced the crystallization capacity of PLA, and improved the thermal properties and flame retardant properties of the prepared composites. The results showed that materials prepared with a BC content of 40 wt% exhibited the best overall performance.

Effects of Reed Biochar Mass Fraction on the Properties of Polypropylene/Reed Char Composites.

Reed charcoal/polypropylene (RC/PP) composites were prepared by melt-blending and molding processes. The effects of RC addition (by mass fraction) on its mechanical properties were investigated and the mechanism characterized. The results showed that RC and PP were physically bonded and formed a mechanical interlocking matrix. The water absorption rate of these composites was <1% at 168 h. As the RC mass fraction increased, the tensile modulus, crystallinity, and energy storage modulus of the composites increased and then decreased, with the tensile modulus reaching a maximum of 679.4 MPa. The thermal decomposition rate peak and starting melt temperature increased by 14.8 and 2.5 °C, respectively, compared to pure PP, and the energy storage modulus reached a maximum of 3752.8 MPa at 40 wt% RC. The addition of RC in appropriate amounts improved the rigidity and thermal stability of these composites.

Recessive PKD1 Mutations Are Associated With Febrile Seizures and Epilepsy With Antecedent Febrile Seizures and the Genotype-Phenotype Correlation.

Objective: The PKD1 encodes polycystin-1, a large transmembrane protein that plays important roles in cell proliferation, apoptosis, and cation transport. Previous studies have identified PKD1 mutations in autosomal dominant polycystic kidney disease (ADPKD). However, the expression of PKD1 in the brain is much higher than that in the kidney. This study aimed to explore the association between PKD1 and epilepsy. Methods: Trios-based whole-exome sequencing was performed in a cohort of 314 patients with febrile seizures or epilepsy with antecedent febrile seizures. The damaging effects of variants was predicted by protein modeling and multiple in silico tools. The genotype-phenotype association of PKD1 mutations was systematically reviewed and analyzed. Results: Eight pairs of compound heterozygous missense variants in PKD1 were identified in eight unrelated patients. All patients suffered from febrile seizures or epilepsy with antecedent febrile seizures with favorable prognosis. All of the 16 heterozygous variants presented no or low allele frequencies in the gnomAD database, and presented statistically higher frequency in the case-cohort than that in controls. These missense variants were predicted to be damaging and/or affect hydrogen bonding or free energy stability of amino acids. Five patients showed generalized tonic-clonic seizures (GTCS), who all had one of the paired missense mutations located in the PKD repeat domain, suggesting that mutations in the PKD domains were possibly associated with GTCS. Further analysis demonstrated that monoallelic mutations with haploinsufficiency of PKD1 potentially caused kidney disease, compound heterozygotes with superimposed effects of two missense mutations were associated with epilepsy, whereas the homozygotes with complete loss of PKD1 would be embryonically lethal. Conclusion: PKD1 gene was potentially a novel causative gene of epilepsy. The genotype-phenotype relationship of PKD1 mutations suggested a quantitative correlation between genetic impairment and phenotypic variation, which will facilitate the genetic diagnosis and management in patients with PKD1 mutations.

AFF2 Is Associated With X-Linked Partial (Focal) Epilepsy With Antecedent Febrile Seizures.

Objective: AFF2 mutations were associated with X-linked intellectual developmental disorder-109 and in males with autism spectrum disorder (ASD). The relationship between AFF2 and epilepsy has not been defined. Method: Trios-based whole-exome sequencing was performed in a cohort of 372 unrelated cases (families) with partial (focal) epilepsy without acquired causes. Results: Five hemizygous missense AFF2 mutations were identified in five males with partial epilepsy and antecedent febrile seizures without intellectual disability or other developmental abnormalities. The mutations did not present in the controls of general populations with an aggregate frequency significantly higher than that in the control populations. Previously, intellectual disability-associated AFF2 mutations were genomic rearrangements and CCG repeat expansion mutations mostly, whereas the mutations associated with partial epilepsy were all missense. Missense AFF2 mutations associated with epilepsy fell into the regions from N-terminal to the nuclear localization signal 1 (NLS1), while ASD-associated missense mutations fell in the regions from NLS1 to C-terminal. Conclusion: AFF2 is potentially a candidate causative gene of X-link partial epilepsy with antecedent febrile seizures. The genotype-phenotype correlation and molecular sub-regional effect of AFF2 help in explaining the mechanisms underlying phenotypic variations.

Improving the effects of ketogenic diet therapy in children with drug-resistant epilepsy.

PURPOSE: To evaluate the retention rate, efficacy, and safety of ketogenic diet therapy for drug-resistant epilepsy in children and compare the results with those of a previous cohort at our institution. METHODS: A total of 634 children with drug-resistant epilepsy were included in this retrospective study. Patients were categorized into two groups. The previous cohort was included as a control group and included 317 children assessed between 2004 and 2011, whereas the current group included 317 children assessed between 2015 and 2019. The control group was provided care as usual, and the current group additionally adopted the goal and long-term management strategy. Outcomes were measured with respect to retention rate, seizure reduction, and adverse reaction. RESULTS: Patient demographics were consistent between both cohorts. Compared to the past ten years, the retention rate significantly increased over time (3 months: 62.8% vs. 82.0%, p <0.001; 6 months: 42.0% vs. 60.6%, p <0.001; 12 months: 24.3% vs. 34.1%, p = 0.007), and the response rate was significantly improved (3 months: 35.0% vs. 55.5%, p <0.001; 6 months: 26.2% vs. 43.2%, p <0.001; 12 months: 18.6% vs. 31.5%, p <0.001). Constipation (n = 79, 24.9%) was the most common side effect in the current cohort. Food refusal and hypoproteinaemia reduced to 3.5% and 0.9%, respectively. CONCLUSION: Goal and long-term management is effective for ketogenic diet therapy, which significantly improved the ketogenic diet retention rate, efficacy, and incidence of adverse reactions. This strategy has promising applicability in ketogenic diet therapy. CLINICAL REGISTRATION: ChiCTR-IIR-16,008,342.

Long-term outcomes of infantile spasms in children treated with ketogenic diet therapy in combination with anti-seizure medications in a resource-limited region.

Objective: Despite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet. Methods: Patients suffering from infantile spasms who had at least 2 years of medical records in the electronic medical record system between January 2014 and August 2022 were included in this study. Patient information was retrospectively reviewed. All patients had received ketogenic diet therapy (mainly classical ketogenic diet therapy). The ketogenic diet therapy was combined with ASMs not used as first-line therapies. The primary endpoint outcome measure was the number of patients with seizure freedom. The secondary measures included the duration of ketogenic diet therapy, choice of ASMs, and patient development at the last visit. Results: A total of 177 patients with infantile spasms were included, and 152 (86%) of them had seizure freedom. The median duration from the first to the last hospital visit was 53.27 months, and the number of visits was 47.00. The median age at the initial hospital visit was 8.00 months, and the median age at initiation of the ketogenic diet was 17.73 months. At the last visit, the proportions of patients with neurodevelopmental delay, developmental epileptic encephalopathy, drug-resistant epilepsy, and generalized seizures increased significantly. The frequently used ASMs were topiramate, valproic acid, levetiracetam, nitrazepam, and vitamin B6 injection, while the recommended first-line drugs corticotropin and vigabatrin were rarely selected. The study duration of 9.5 years was divided into three periods but the prescription of ASMs did not change significantly between these periods. Conclusions: Although the seizure freedom rate was high with ketogenic diet therapy combined with non-standard ASMs, the patients had a significant neurodevelopmental delay at the last visit, which was, however, similar to that of standard treatment. To improve the outcomes of infantile spasms, multicenter clinical trials of the ketogenic diet as a first-line treatment in combination with non-standard ASMs are needed.

Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study.

The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling. We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed. Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy. The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses. Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy.

Genotype-phenotype analysis in Mowat-Wilson syndrome associated with two novel and two recurrent ZEB2 variants.

The current study aimed to analyze the genotype-phenotype relationship in patients with variants of zinc finger E box-binding homeobox 2 (ZEB2), which is a gene encoding a homeobox transcription factor known to be mutated in Mowat Wilson syndrome (MWS). Whole genome sequencing (WGS) was performed in 530 children, of whom 333 had epilepsy with or without developmental delay and 197 developmental delay alone. Pathogenic variants were identified and verified using Sanger sequencing, and the disease phenotypes of the corresponding patients were analyzed for features of MWS. WGS was performed in 333 children with epilepsy, with or without developmental delays or intellectual disability and 197 children with developmental delay alone. A total of 4 unrelated patients were indicated to be heterozygous for truncating mutations in ZEB2. A total of three of these were nonsense mutations (novel Gln1072X and recurrent Trp97X and Arg921X), and one was a frameshift mutation (novel Val357Aspfs*15). The mutations have occurred de novo as confirmed by Sanger sequence comparisons in patients and their parents. All 4 patients exhibited signs of MWS, whereby the severity increased the closer a mutation was located to the amino terminus of the protein. The results suggest that the clinical outcome in MWS depends on the relative position of the truncation in the ZEB2 gene. A number of interpretations of this genotype/phenotype association are discussed in the present study.

Abnormalities of Cortical Thickness in Pediatric Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

OBJECTIVE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common intractable seizure type of pediatric epilepsy, with alterations in the cortex across the whole brain. The aim of this study is to investigate the abnormalities of cortical thickness in pediatric MTLE-HS. METHODS: Subjects were recruited from Shenzhen Children's Hospital between September 2015 and December 2016. MTLE was confirmed by the experienced neurological physician based on International League Against Epilepsy (ILAE) diagnosis criteria, and structural magnetic resonance imaging (MRI) was performed at 3T for quantitative assessment of cortical thickness. A general linear model with age and gender as covariates was used to examine the vertex-wise differences in cortical thickness between 1) left MTLE-HS (LMTLE-HS) and healthy controls (HC), and 2) right MTLE-HS (RMTLE-HS) and HC. The family-wise error corrected significance threshold was set at P < 0.05. Through a combination of probability and cluster-size thresholding, cluster-wise P values were obtained for the resulting clusters. RESULTS: 13 LMTLE-HS, 6 RMTLE-HS, and 20 age-matched HC were finally enrolled in the study. No significant difference in the mean age (LMTLE-HS vs. HC, p=0.57; RMTLE-HS vs. HC, p=0.39) and gender ratio (LMTLE-HS vs. HC, p=0.24; RMTLE-HS vs. HC, p=0.72) was found between MTLE-HS and HC. In LMTLE-HS, cortical thickness was found significantly decreased in the ipsilateral caudal middle frontal gyrus (p=0.012) and increased in the contralateral inferior temporal gyrus (p=0.020). In RMTLE-HS, cortical thickness significantly decreased in the ipsilateral posterior parietal lobe (superior, p<0.001 and inferior parietal gyrus, p=0.03), the anterior parietal lobe (postcentral gyrus, p=0.006), the posterior frontal lobe (precentral gyrus, p=0.04 and the lateral occipital gyrus, p<0.001), and the contralateral lateral occipital gyrus, middle frontal (p<0.0001) and superior frontal gyrus (p<0.001), and pericalcarine cortex (p=0.020). CONCLUSION: We detected significant cortical abnormalities in pediatric MTLE-HS patients compared with HC. These cortical abnormalities could be explained by specific pathogenesis in MTLE-HS, and may finally contribute to understanding the intrinsic mechanism of MTLE-HS.

Voxel-based morphometry analysis and machine learning based classification in pediatric mesial temporal lobe epilepsy with hippocampal sclerosis.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common type of pediatric epilepsy. We sought to evaluate whether the combination of voxel-based morphometry (VBM) and support vector machine (SVM), a machine learning method, was feasible for the classification of MTLE-HS. Three-dimensional T1-weighted MRI was acquired in 37 participants including 22 with MTLE-HS (16 left, 6 right) and 15 healthy controls (HCs). VBM was used to detect the regions of gray matter volume (GMV) abnormalities. The volumes of these regions were then calculated for each participant and used as the features in SVM. The SVM model was trained and tested with leave-one-out cross validation (LOOCV). We performed VBM-based comparison and SVM-based classification between left HS (LHS) and HC as well as between right HS (RHS) and HC. Both GMV increase and reduction were found in the group comparisons with VBM. Using SVM, we reached an area under the receiver operating characteristic curve (AUC) of 0.870, 0.976 and 0.902 for the classification between LHS and HC, between RHS and HC and between HS and HC respectively. The VBM findings were concordant with the clinical findings. Thus, our proposed method combining VBM findings with SVM, were applicable in the classification of padiatric MTLE-HS with high accuracy.

Improving brain function of pediatric acute lymphoblastic leukemia patients after induction chemotherapy, a pilot self-contrast study by fractional amplitude of low-frequency fluctuation.

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.

Meta-analysis of voxel-based morphometry studies of gray matter abnormalities in patients with mesial temporal lobe epilepsy and unilateral hippocampal sclerosis.

We aimed to perform a meta-analysis to systematically determine the most consistent regions of gray matter volume (GMV) abnormality in patients of unilateral mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), and to reveal the difference of GMV abnormality between the patients with left-sided and right-sided MTLE-HS. A comprehensive and systematic search was performed in PubMed for voxel-based morphometry (VBM) studies of MTLE-HS. A total of 12 MTLE-HS studies, including 9 left-sided MTLE-HS (LMTLE-HS) and 8 right-sided MTLE-HS (RMTLE-HS) studies were included. The activation likelihood estimation (ALE) method was applied in our meta-analysis. Compared to the healthy controls, MTLE-HS patients showed significant GMV decrease in the parahippocampal gyrus, left pulvinar and right pyramis. For LMTLE-HS, the most consistent GMV decrease was detected in the left parahippocampal gyrus. For RMTLE-HS, the most consistent GMV decrease was found in the right parahippocampal gyrus. No shared regions of significant GMV reduction were found between LMTLE-HS and RMTLE-HS either. This meta-analysis revealed that MTLE-HS patients had significant GMV reduction even beyond the hippocampus, and the subtypes showed distinct reduction patterns. Our findings, if were further verified with larger samples, would have implications for the clinical diagnosis of MTLE-HS.

Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

OBJECTIVE: Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. METHODS: In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. RESULTS: The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. CONCLUSION: The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia.

[Brain injury after induction chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the changes in brain injury after the induction chemotherapy in children with acute lymphoblastic leukemia (ALL) by cranial MRI. METHODS: The clinical data and cranial MRI results of 62 children with ALL who were hospitalized from March 2014 to June 2015 were analyzed retrospectively. RESULTS: Before chemotherapy, MRI showed bone marrow infiltration of the skull in 33 patients (53%); the children with WBC<20×10(9)/Lhad a significantly lower incidence rate of bone marrow infiltration of the skull than those with WBC≥20×10(9)/L (16 patients/42% vs 17 patients/71%; P<0.05), and the high-risk group had a significantly higher incidence rate of bone marrow infiltration of the skull than the non-high-risk group (71% vs 44%; P<0.05). Before chemotherapy, there were 4 cases (7%) of brain atrophy, and 2 cases (3%) of abnormal signals in the sensory conduction bundle. MRI reexamination in 28 patients after 3 months of chemotherapy showed 3 new cases (11%) of brain atrophy and 1 aggravated case of brain atrophy. CONCLUSIONS: The children with ALL have bone marrow infiltration of the skull, brain atrophy, and abnormal signals in the sensory conduction bundle before chemotherapy, especially bone marrow infiltration of the skull, and some changes in brain injury disappear after treatment.

Importance of spondin 1 and cellular retinoic acid binding protein 1 in the clinical diagnosis of ovarian cancer.

BACKGROUND: Diagnosis of ovarian cancer is often delayed because of subtle symptoms and a lack of a specific, sensitive test useful for the general population. The majority of cases are diagnosed at late stages, after the tumor has metastasized and implanted on many other abdominal organs and cavity surfaces. A paucity of prognostic markers makes it difficult to define which tumors will act aggressively and shorten survival. Hence, it is imperative to have new screening tests for diagnosis of ovarian cancer at earlier stages, prior to metastatic progression. Diagnosis at these early stages will dramatically increase the overall survival of women with ovarian cancer. MATERIAL AND METHODS: Based on previously published literature on proposed molecular cell markers in ovarian carcinoma, we sought to validate the overexpression of two genes (cellular retinoic acid Binding Protein, CRABP-1, and spondin 1) through immunohistochemistry. RESULTS: We verified the overexpression of spondin 1 in ovarian cancer. Expression of cellular retinoic acid Binding Protein, CRABP-1 in whole ovarian cancer tissue sections was higher than in the TMA tissue cores. CONCLUSION: Our results thus demonstrate that spondin 1 is a useful marker for ovarian cancer; additionally, the high percentages of tumors that are positive for spondin 1 make it an ideal target for therapy. CRABP-1 was not expressed at high levels in any subtype of ovarian cancer, making it a poor marker.