Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients.

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

Individual-based morphological brain network changes in children with Rolandic epilepsy.

OBJECTIVE: To investigate the local cortical morphology and individual-based morphological brain networks (MBNs) changes in children with Rolandic epilepsy (RE). METHODS: Based on the structural MRI data of 56 children with RE and 56 healthy controls (HC), we constructed four types of individual-based MBNs using morphological indices (cortical thickness [CT], fractal dimension [FD], gyrification index [GI], and sulcal depth [SD]). The global and nodal properties of the brain networks were analyzed using graph theory. The between-group difference in local morphology and network topology was estimated, and partial correlation analysis was further analyzed. RESULTS: Compared with the HC, children with RE showed regional GI increases in the right posterior cingulate gyrus and SD increases in the right anterior cingulate gyrus and medial prefrontal cortex. Regarding the network level, RE exhibited increased characteristic path length in CT-based and FD-based networks, while decreased FD-based network node efficiency in the right inferior frontal gyrus. No significant correlation between altered morphological features and clinical variables was found in RE. CONCLUSIONS: These findings indicated that children with RE have disrupted morphological brain network organization beyond local morphology changes. SIGNIFICANCE: The present study could provide more theoretical basis for exploring the neuropathological mechanisms in RE.

Systematically altered connectome gradient in benign childhood epilepsy with centrotemporal spikes: Potential effect on cognitive function.

OBJECTIVE: Benign childhood epilepsy with centrotemporal spikes (BECTS) affects brain network hierarchy and cognitive function; however, itremainsunclearhowhierarchical changeaffectscognition in patients with BECTS. A major aim of this study was to examine changes in the macro-network function hierarchy in BECTS and its potential contribution to cognitive function. METHODS: Overall, the study included 50 children with BECTS and 69 healthy controls. Connectome gradient analysis was used to determine the brain network hierarchy of each group. By comparing gradient scores at each voxel level and network between groups, we assessed changes in whole-brain voxel-level and network hierarchy. Functional connectivity was used to detect the functional reorganization of epilepsy caused by these abnormal brain regions based on these aberrant gradients. Lastly, we explored the relationships between the change gradient and functional connectivity values and clinical variables and further predicted the cognitive function associated with BECTS gradient changes. RESULTS: In children with BECTS, the gradient was extended at different network and voxel levels. The gradient scores frontoparietal network was increased in the principal gradient of patients with BECTS. The left precentral gyrus (PCG) and right angular gyrus gradient scores were significantly increased in the principal gradient of children with BECTS. Moreover, in regions of the brain with abnormal principal gradients, functional connectivity was disrupted. The left PCG gradient score of children with BECTS was correlated with the verbal intelligence quotient (VIQ), and the disruption of functional connectivity in brain regions with abnormal principal gradients was closely related to cognitive function. VIQ was significantly predicted by the principal gradient map of patients. SIGNIFICANCE: The results indicate connectome gradient disruption in children with BECTS and its relationship to cognitive function, thereby increasing our understanding of the functional connectome hierarchy and providing potential biomarkers for cognitive function of children with BECTS.

An efficient biosensor using a functionalized microneedle of Cu2O-based CoCu-LDH for glucose detection.

Glucose detection with small and micro volume sampling has recently received increasing attention in monitoring personal health. Herein, a cauliflower-type cluster of Cu2O nanoparticles (NPs) was directly deposited on the tip surface of a stainless steel acupuncture needle electrode (ANE) by electrochemical deposition, and then this pre-formed cuprous basis was used to further prepare the neatly arranged CoCu-layered double hydroxide (CoCu-LDH) nanosheets that interconnected to form nano-sized pores in the range from 100 to 500 nm. The microstructure and spectral characteristics of the surface modification materials were comprehensively characterized by FE-SEM, EDS, XRD, FT-IR and TEM. Cu2O-based CoCu-LDH composites with special morphology had been proven to accelerate the rate of electron transport and provide more available active centers, and moreover, the mixed valence of Cu/Co induced an excellent synergism for the electrocatalytic oxidation of glucose. As a result, CoCu-LDH/Cu2O/ANE as a sensitive glucose probe exhibited two wider linear ranges of 0.03-0.40 mM and 0.40-6.00 mM, with sensitivities of 116.13 µA mM-1 and 52.08 µA mM-1, respectively, and the detection limit as low as 0.46 µM (S/N = 3). The response time only took 3 s and it kept working stably in the interference of ascorbic acid (AA), dopamine (DA), uric acid (UA), and Cl-. In the stability test, the CoCu-LDH/Cu2O/ANE sensor exhibited a stable monitoring sensitivity after 15 days. Finally, the CoCu-LDH/Cu2O/ANE sensor had been successfully applied to glucose analysis in human serum, proving that our design was an attractive strategy for developing a portable, minimally invasive, and low-cost non-enzymatic electrochemical glucose sensing platform.

Structural and functional changes in drug-naïve benign childhood epilepsy with centrotemporal spikes and their associated gene expression profiles.

Benign epilepsy with centrotemporal spikes (BECTS) is a common pediatric epilepsy syndrome that has been widely reported to show abnormal brain structure and function. However, the genetic mechanisms underlying structural and functional changes remain largely unknown. Based on the structural and resting-state functional magnetic resonance imaging data of 22 drug-naïve children with BECTS and 33 healthy controls, we conducted voxel-based morphology (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) analyses to compare cortical morphology and spontaneous brain activity between the 2 groups. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging spatial correlation analyses were applied to explore gene expression profiles associated with gray matter volume (GMV) and fALFF changes in BECTS. VBM analysis demonstrated significantly increased GMV in the right brainstem and right middle cingulate gyrus in BECTS. Moreover, children with BECTS exhibited significantly increased fALFF in left temporal pole, while decreased fALFF in right thalamus and left precuneus. These brain structural and functional alterations were closely related to behavioral and cognitive deficits, and the fALFF-linked gene expression profiles were enriched in voltage-gated ion channel and synaptic activity as well as neuron projection. Our findings suggest that brain morphological and functional abnormalities in children with BECTS involve complex polygenic genetic mechanisms.

Abnormalities of hemispheric specialization in drug-naïve and drug-receiving self-limited epilepsy with centrotemporal spikes.

PURPOSE: Self-limited epilepsy with centrotemporal spikes (SLECTS) is a pediatric benign epilepsy but often accompanied by subsequent (in adulthood) functional changes such as language, which are thought to have distinct areas of hemispheric lateralization and functional differentiation. This study aimed to explore hemispheric specialization measured by resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity in drug-naïve and drug-receiving SLECTS. METHODS: Hemispheric specialization was quantified in three groups of children, including 21 drug-naïve patients (DNP) with SLECTS, 34 drug-receiving patients (DRP) with SLECTS and 36 demographically matched typical development (TD). RESULTS: Compared with the TD group, both the DNP and DRP groups exhibited significantly higher specialization in the left superior temporal gyrus, right parahippocampus, left putamen, and right caudate. The DNP group exhibited significantly higher hemispheric specialization in the right precentral gyrus and right inferior temporal gyrus, while the DRP group demonstrated significantly higher hemispheric specialization in the left postcentral gyrus and right hippocampus than the TD group. Furthermore, bilateral cerebellum_6 showed opposing hemispheric specialization trends in the two patient groups. Further meta-analytical mapping demonstrated that hemispheric specialization-related differential brain regions are primarily involved in language processing. CONCLUSION: Our findings showed that children with SLECTS had altered hemispheric specialization, mainly in language processing regions, suggesting both abnormal intrahemispheric segregation and interhemispheric integration in these children.

Disrupted functional connectivity patterns of the left inferior frontal gyrus subregions in benign childhood epilepsy with centrotemporal spikes.

Background: Benign epilepsy with centrotemporal spikes (BECTS) is one of the most common pediatric epileptic syndromes. Recent studies have shown that BECTS can lead to significant language dysfunction. Although research supports the role of the left inferior frontal gyrus (LIFG) in BECTS, it is unclear whether the subregions of the LIFG show different change patterns in patients with this syndrome. Methods: Using resting-state functional magnetic resonance imaging (fMRI) data in a group of 49 BECTS patients and 49 healthy controls, we investigated whether the BECTS patients show abnormal connectivity patterns of the LIFG subregions. Results: Compared with healthy controls, the BECTS patients exhibited higher connectivity between the following: the inferior frontal sulcus (IFS) and the right anterior cingulate cortex (ACC), and the ventral area 44 (A44v) region and the left hippocampus/parahippocampus. Also, a decreased connectivity was found between the IFS and the left inferior temporal gyrus (ITG). No other significant differences in functional connectivity were found in the other 4 functional subregions of the LIFG in the BECTS. Conclusions: These findings provide evidence for BECTS-related functional connectivity patterns of the LIFG subregions and suggest that different subregions may be involved in different neural circuits associated with language function in the BECTS.

Abnormal percent amplitude of fluctuation and functional connectivity within and between networks in benign epilepsy with centrotemporal spikes.

BACKGROUND: Benign epilepsy with centrotemporal spikes (BECTS) is one of the most common childhood epilepsy syndromes. The neural basis of BECTS is still poorly understood. This study aimed to further investigate the possible neural mechanisms of BECTS by comparing percent amplitude of fluctuation (PerAF) of resting-state functional magnetic resonance imaging (RS-fMRI) signal of each brain voxel and connectivity within and between related networks in children with BECTS and healthy controls (HCs). METHODS: Firstly, we used PerAF method to investigate brain functional alteration and defined the regions of interest (ROIs) where children with BECTS exhibited significant PerAF alterations compared to HCs. We then divided these ROIs into different networks based on previous findings and investigated alterations of functional connectivity within and between networks in children with BECTS. Receiver operating characteristic (ROC) curve was employed to assess the reliable biomarker for distinguishing children with BECTS from HCs based on the intergroup PerAF differences. RESULTS: Children with BECTS showed decreased PerAF in the left middle frontal cortex (MFC), right precentral gyrus, left precuneus (PCUN), bilateral posterior cingulate cortex (PCC), left angular gyrus, left inferior parietal lobule (IPL), right supplementary motor area (SMA) and left primary somatosensory cortex (S1) compared to HCs. The IPL and PCC exhibited higher classification power by ROC analysis. Moreover, our findings exhibited increased Intra-network connectivity in the default mode network (DMN), and increased inter-network connectivity of the sensorimotor network (SMN) with Broca's area and DMN. CONCLUSIONS: Our study investigated the abnormal PerAF and functional brain networks in children with BECTS, which might provide new insights into the pathological mechanisms of BECTS.

Prediction of Communication Impairment in Children With Bilateral Cerebral Palsy Using Multivariate Lesion- and Connectome-Based Approaches: Protocol for a Multicenter Prospective Cohort Study.

BACKGROUND: Bilateral cerebral palsy (BCP) is the most common type of CP in children and is often accompanied by different degrees of communication impairment. Several studies have attempted to identify children at high risk for communication impairment. However, most prediction factors are qualitative and subjective and may be influenced by rater bias. Individualized objective diagnostic and/or prediction methods are still lacking, and an effective method is urgently needed to guide clinical diagnosis and treatment. The aim of this study is to develop and validate an objective, individual-based model for the prediction of communication impairment in children with BCP by the time they enter school. METHODS: A multicenter prospective cohort study will be conducted in four Chinese hospitals. A total of 178 children with BCP will undergo advanced brain magnetic resonance imaging (MRI) at baseline (corrected age, before the age of 2 years). At school entry, communication performance will be assessed by a communication function classification system (CFCS). Three-quarters of children with BCP will be allocated as a training cohort, whereas the remaining children will be allocated as a test cohort. Multivariate lesion- and connectome-based approaches, which have shown good predictive ability of language performance in stroke patients, will be applied to extract features from MR images for each child with BCP. Multiple machine learning models using extracted features to predict communication impairment for each child with BCP will be constructed using data from the training cohort and externally validated using data from the test cohort. Prediction accuracy across models in the test cohort will be statistically compared. DISCUSSION: The findings of the study may lead to the development of several translational tools that can individually predict communication impairment in children newly diagnosed with BCP to ensure that these children receive early, targeted therapeutic intervention before they begin school. TRIAL REGISTRATION: The study has been registered with the Chinese Clinical Trial Registry (ChiCTR2100049497).

Connectome-based prediction of brain age in Rolandic epilepsy: a protocol for a multicenter cross-sectional study.

BACKGROUND: Rolandic epilepsy (RE) is a common pediatric idiopathic partial epilepsy syndrome. Children with RE display varying degrees of cognitive impairment. In epilepsy, age-related neuroanatomic and cognitive changes differ greatly from those observed in the healthy brain, and may be defined as accelerated brain aging. Connectome-based predictive modeling (CPM) is a recently developed machine learning approach that uses whole-brain connectivity measured with neuroimaging data ("neural fingerprints") to predict brain-behavior relationships. The aim of the study will be to develop and validate a CPM for predicting brain age in patients with RE. METHODS: A multicenter, cross-sectional study will be conducted in 5 Chinese hospitals. A total of 100 RE patients (including 50 patients receiving anti-epileptic drugs and 50 drug-naïve patients) and 100 healthy children will be recruited to undergo a neuropsychological test using the Wechsler Intelligence Scale. Magnetic resonance images will also be collected. CPM will be applied to predict the brain age of children with RE based on brain functional connectivity. DISCUSSION: The findings of the study will facilitate our understanding of developmental changes in the brain in children with RE and could also be an important milestone in the journey toward developing effective early interventions for this disorder. TRIAL REGISTRATION: The study has been registered with Chinese Clinical Trial Registry (ChiCTR2000032984).

Surface-based morphometry study of the brain in benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: The study aimed to explore cortical morphology in benign childhood epilepsy with centrotemporal spikes (BECTS) and the relationship between cortical characteristics and age of onset and intelligence quotient (IQ). METHODS: Cortical morphometry with surface-based morphometry (SBM) was used to compare changes in cortical thickness, gyrification, sulcal depth, and fractal dimension of the cerebral cortex between 25 BECTS patients and 20 healthy controls (HCs) with two-sample t-tests [P<0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical morphological changes and age of onset and IQ, which included verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were investigated with Spearman correlation analysis (P<0.05, uncorrected). RESULTS: The BECTS patients showed extensive cortical thinning predominantly in bilateral frontal, temporal regions, and limbic system. Cortical gyrification increased in the left hemisphere and partial right hemisphere, and the decreased cortical gyrification was only in the left hemisphere. The increased sulcal depth was the left fusiform gyrus. There are no statistically significant differences in the fractal dimension. Correlation analysis revealed the negative correlation between age of onset and cortical thickness in the right precentral gyrus. It also revealed the negative correlation between the age of onset and cortical gyrification in the left inferior parietal gyrus. Also, there was negative correlation between VIQ and cortical gyrification in the left supramarginal gyrus of BECTS patients. CONCLUSIONS: This study reveals aberrant cortical thickness, cortical gyrification, and sulcal depth of BECTS in areas related to cognitive functions including language, attention and memory, and the correlation between some brain regions and VIQ and age of onset, providing a potential marker of early neurodevelopmental disturbance and cognitive dysfunction in BECTS.

Teratoma of the adrenal gland: clinical experience and literature review.

Teratoma originates from pluripotent cells of two or more than two germ cell layers, and most of them are benign. Teratomas are found in the ovaries and testes. Retroperitoneal teratoma is rare, especially adrenal teratoma. Here, we describe a rare case of a 17-year-old woman who was diagnosed with pulmonary tuberculosis and a right adrenal mass at the age of eight. So, she received anti-tuberculosis treatment. Nine years later, chest X-rays showed prior lesions in both lungs, and abdominal CT showed the mass in the right adrenal gland was larger than before, during this period she had no clinical symptoms. She underwent retroperitoneal laparoscopic adrenalectomy, and the pathological diagnosis was a mature teratoma of the right adrenal gland. During a one-year follow-up, the patients recovered well without any discomfort. Thirty-two cases were found in the literature review, among which no patients had a history of pulmonary tuberculosis. Adrenal teratoma is often seen in females and the left adrenal gland. The imaging features of adrenal teratoma can be cystic, solid, and cystic solids. Mature fat and calcification can be seen in most teratomas. Comprehensive analysis of clinical features and imaging characteristics can enhance the diagnostic confidence of radiologists in adrenal teratoma.

Angiomyolipoma of the adrenal gland: clinical experience and literature review.

Angiomyolipomas, a type of benign mesenchymal tumor originating from perivascular epithelioid cells, are composed of mature adipose tissue, smooth muscle, and thick-walled vessels. With fewer than 20 cases reported in English literature, adrenal angiomyolipoma is extremely rare. In these cases, the patient is usually asymptomatic and the tumor is found incidentally. Adrenal angiomyolipoma has never been reported in association with lung cancer. A 62-year-old man presented with an enlarged mass in the left adrenal gland. The mass had persisted for two years previously and was first discovered during a routine follow-up CT examination after lung cancer resection in 2016. Subsequently, partial left adrenal resection was performed. Postoperative histopathology confirmed a benign angiomyolipoma comprising adipose tissue, blood vessels, and smooth muscle cells. At three months follow-up, the patient was alive and had experienced no recurrence after the operation. Eighteen cases were identified on literature review, among which no patients had a history of lung cancer. These cases occurred more often in females and lesions mostly located on the right side. All of the reported cases were nonfunctional, ranging in size from 0.2 to 16 cm (95% of the masses exceeding 4 cm). In this case report, we consider a rare case of a patient with an adrenal angiomyolipoma with a history of lung cancer. Adrenal angiomyolipoma should be considered as one of the differential diagnoses of adrenal metastasis for patients with a history of primary tumors.

CT and MRI of adrenal gland pathologies.

Besides ultrasound and nuclear medicine techniques, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used to examine adrenal lesions in both symptomatic and asymptomatic patients. Some adrenal lesions have characteristic radiological features. If an adrenal nodule is discovered incidentally, determining whether the lesion is benign or malignant is of great importance. According to their biological behavior, lesions can be divided into benign (mainly: adenoma, hyperplasia, pheochromocytoma, cyst, hemorrhage, cystic lymphangioma, myelolipoma, hemangioma, ganglioneuroma, teratoma) and malignant (mainly: metastases, adrenal cortical carcinoma, neuroblastoma, lymphoma) conditions. In this paper, we review CT/MRI findings of common adrenal gland lesions.

Purification of Protein Disulfide-isomerase from Human Liver and Preparation of Its Antiserum.

Protein disulfide-isomerase has been isolated from human liver. The preparative procedure involved heat treatment, (NH(4))(2)SO(4) precipitation, CM-Sephadex C50 and DEAE-fast flow chromatography. The enzyme was homogenous and had a molecular mass of 60 kD or 120 kD as determined by sodium dodecy1 sulphate electro-phoresis and gel filtration respectively, indicating that the enzyme was a 120 kD dimmer with a subunit with molecular mass of 60 kD. The enzyme activity was as high as 830 U/g.protein as measured by the reactivation of "scrambled" ribonuclease. The antiserum of high titer was prepared by immunizing New Zealand rabbit with a mixture of the protein disulfide-isomerase and adjuvant.