Normal Brain Research Articles

Diagnosis and Treatment of Spontaneous Intracranial Hypotension: Role of Epidural Blood Patching.

This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Neurobehavioral perspectives on autistic spectrum disorder

Understanding genetics and environmental influences in autism has been explored in greater depth in recent decades. However, the mechanism by which they converge that leads to autism still needs to be explored further. An autism diagnosis in DSM-5 results from a neurodevelopmental disorder hurting normal brain function, affecting communication and social interaction combined with restricted or repetitive patterns of behavior and interests. This paper reviews current work investigating how the underlying mechanism of the brain structure and function relates to the complex and aberrant behavioral manifestations of autism. Mapping this connection can provide us with a better understanding of autism signs and symptoms, making the process of accurate diagnosis more straightforward. As a complex neurobehavioral condition, autistic individuals process the environment and their interactions with others differently from those without autism. So, they make different perceptions and connections between themselves and the environment. Consequently, they will have difficulty communicating, forming relationships, and responding appropriately to their environment. It is this lifelong neurobehavioral dysfunction that prevents autistic individuals from adequately understanding what they perceive and the emotional expression of others. There will be differences in their mental states, how their brains work, and how their thinking processes will be affected by a neurodevelopmental disability.

Molecular landscape of glucose metabolism in glioblastoma and the normal human brain: A narrative review

Abstract Glioblastoma multiforme (GBM) is one of the most aggressive tumors known to occur in the brain. Metabolism is one of the driving factors enabling the successful proliferation of tumor cells, thus increasing the tumor mass. Tumor metabolism is now recognized as a major hallmark of oncogenesis. Since the brain largely relies on its glucose supply for growth, glucose metabolism significantly contributes to oncogenesis in brain cancers. Here, we review the major metabolic pathways seen in normal brain physiology in addition to the Warburg effect, aberrant tricarboxylic acid cycle, and oxidative phosphorylation observed in GBM. We highlight the important differences in glucose metabolism between the normal and cancerous environments. In addition, we provide insights into lactate shuttling, the pentose phosphate pathway, and immune interactions with glucose metabolism, which drive the nutritional pathways in both the normal and cancerous environment.

MAPPING THYROID HORMONE ACTION IN THE HUMAN BRAIN.

Normal brain development, mood, and cognitive functions depend on thyroid hormone (TH) action. However, little is known about how TH mediates its actions in the human brain. This is because of limited access to human brains deprived of TH during fetal and early postnatal life, as well as from adults with altered thyroid status. One way to partially bypass these limitations is by using magnetic resonance imaging and spectroscopy, two neuroimaging techniques that provide detailed, non-invasive information on human brain structure and function. Another way is using human-induced pluripotent stem cells (hiPSCs)-derived three-dimensional in vitro systems, known as brain organoids, which allow for studying fundamental aspects of the early stages of human brain development. This narrative review focuses on neuroimaging and brain organoid studies. Neuroimaging of human brains performed in individuals with different thyroid conditions provides information on the volume, myelination, blood flow, neural activity, and connectivity of different areas. Such studies show that a suboptimal thyroid status can impact human brain development and its normal function throughout life. This is true not only for patients with sporadic congenital hypothyroidism, during pregnancy or early after birth, but also for adult patients with hypo- or hyperthyroidism and for patients carrying mutations that manifest as impaired sensitivity to TH-and even for normal individuals during aging. Studies using brain organoids generated from iPSCs of healthy individuals or patients with thyroid genetic conditions provide insights into how TH can impact the early development of the human cerebral cortex. The developmental alterations in children born to mothers with different degrees of gestational hypothyroidism or who developed hypothyroidism early in life are remarkable, affecting multiple brain regions and pathways, including the cerebral cortex, hippocampus, cerebellum, interhemispheric and corticospinal tracts, and associative nuclei. The data connecting such changes to poor neurological outcomes in adult patients with hypothyroidism represent an objective link between thyroid-specific functional brain alterations and behavior. Growing brain organoids require TH, proving critical for human neuro- and oligodendrogenesis. These models proved useful in screening drugs with potential therapeutics for patients with genetic thyroid diseases.

Identification of Population-Specific Novel Protein Biomarkers and Possible Therapeutic Targets in Gliomas by Proteomics Approach

Abstract Objective To analyze the differential proteomic profile of gliomas in patients from South India and to identify novel protein glioma biomarkers and possible therapeutic targets to tailor the treatment to individual patients. Material and Methods We have prospectively analyzed the differential proteomic profile of 34 patients with glioma imaging characteristics and compared them with that of normal brain tissue. This research was conducted at the Institute of Neurosurgery, Madras Medical College, in technical collaboration with the Indian Institute of Technology, Madras, over 1 year. Statistical Analysis Biological variate analysis (I-ANALYSIS OF VARIANCE (ANOVA)) was used, with p-value less than 0.05 being significant. Results Twenty proteins (10 upregulated and 10 downregulated) were differentially expressed in tumor tissue. The expression of three pro-apoptotic proteins was downregulated and the expression of three anti-apoptotic proteins was upregulated with statistical significance. The cellular functions of the 20 differentially regulated proteins were subjected to pathway analysis revealing significant alterations in heme biosynthesis, deoxyribonucleic acid (DNA) replication, fibroblast growth factor (FGF) signaling, and epidermal growth factor (EGF0 receptor signaling in glioma. Conclusion KRT18, PRS4, and EF1A2 are anti-apoptotic proteins and are significantly upregulated in gliomas. EARS2, COX5A, and LSM3 are pro-apoptotic proteins, and are significantly downregulated in gliomas. This subverts the apoptotic pathways resulting in prolonged cell survival. This study's statistically significant dysregulation of these six proteins was unique, suggesting that they might be considered population-specific biomarkers and possible therapeutic targets for patients from South India. Abnormalities of heme biosynthesis at the proteomic level were identified in this study, which has not been very well studied previously.

CVG-Net: novel transfer learning based deep features for diagnosis of brain tumors using MRI scans

Brain tumors present a significant medical challenge, demanding accurate and timely diagnosis for effective treatment planning. These tumors disrupt normal brain functions in various ways, giving rise to a broad spectrum of physical, cognitive, and emotional challenges. The daily increase in mortality rates attributed to brain tumors underscores the urgency of this issue. In recent years, advanced medical imaging techniques, particularly magnetic resonance imaging (MRI), have emerged as indispensable tools for diagnosing brain tumors. Brain MRI scans provide high-resolution, non-invasive visualization of brain structures, facilitating the precise detection of abnormalities such as tumors. This study aims to propose an effective neural network approach for the timely diagnosis of brain tumors. Our experiments utilized a multi-class MRI image dataset comprising 21,672 images related to glioma tumors, meningioma tumors, and pituitary tumors. We introduced a novel neural network-based feature engineering approach, combining 2D convolutional neural network (2DCNN) and VGG16. The resulting 2DCNN-VGG16 network (CVG-Net) extracted spatial features from MRI images using 2DCNN and VGG16 without human intervention. The newly created hybrid feature set is then input into machine learning models to diagnose brain tumors. We have balanced the multi-class MRI image features data using the Synthetic Minority Over-sampling Technique (SMOTE) approach. Extensive research experiments demonstrate that utilizing the proposed CVG-Net, the k-neighbors classifier outperformed state-of-the-art studies with a k-fold accuracy performance score of 0.96. We also applied hyperparameter tuning to enhance performance for multi-class brain tumor diagnosis. Our novel proposed approach has the potential to revolutionize early brain tumor diagnosis, providing medical professionals with a cost-effective and timely diagnostic mechanism.

Evaluating intraoperative ultrasound (IOUS) in focal cortical dysplasia (FCD) resection surgery: A systematic review

Background: Surgery is the best approach to treating focal cortical dysplasia (FCD)-related epilepsy; yet, it has suboptimal outcomes because distinguishing the boundaries between the FCD region and normal brain tissue intraoperatively poses a challenge. The use of intraoperative ultrasound (IOUS) helps demarcate FCD lesion borders leading to more accurate intraoperative resection. In this review, the use of IOUS for the resection of FCD was evaluated. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Medline, Embase, Cochrane Library, Scopus Library, and Dynamed Library databases were searched, and two independent reviewers examined the articles. The search terms related to “drug-resistant epilepsy” and “intraoperative ultrasound.” The results between January 2008 and April 2022 were abridged for FCD type, ultrasound resolution, extent of lesion resection, correction of brain shift, postoperative neurological deficits, and postoperative seizure freedom (Engel classification). Results: Ten articles were included in the study. The parameters used to assess the efficacy of IOUS in FCD surgery were ultrasound resolution, demarcation of lesion boundaries, correction of brain shift, postoperative neurological deficits, and seizure freedom. Most studies have shown that IOUS produces high-resolution images. Surgery for Type 2 FCD patients had better outcomes than surgery for Type 1 FCD patients due to better visualization by IOUS. Patients were classified as Engel class 1 or class 2 postoperatively. Eight studies found that IOUS was superior to magnetic resonance imaging in brain shift correction. Conclusion: The preliminary results look promising, especially for the international league against epilepsy class 2 FCD. However, there is a need for more high-quality research evaluating the use of IOUS in FCD and comparing it to other intraoperative imaging modalities.

MAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer

Maturation of eukaryotic pre-mRNAs via splicing and polyadenylation is modulated across cell types and conditions by a variety of RNA-binding proteins (RBPs). Although there exist over 1,500 RBPs in human cells, their binding motifs and functions still remain to be elucidated, especially in the complex environment of tissues and in the context of diseases. To overcome the lack of methods for the systematic and automated detection of sequence motif-guided pre-mRNA processing regulation from RNA sequencing (RNA-Seq) data we have developed MAPP (Motif Activity on Pre-mRNA Processing). Applying MAPP to RBP knock-down experiments reveals that many RBPs regulate both splicing and polyadenylation of nascent transcripts by acting on similar sequence motifs. MAPP not only infers these sequence motifs, but also unravels the position-dependent impact of the RBPs on pre-mRNA processing. Interestingly, all investigated RBPs that act on both splicing and 3’ end processing exhibit a consistently repressive or activating effect on both processes, providing a first glimpse on the underlying mechanism. Applying MAPP to normal and malignant brain tissue samples unveils that the motifs bound by the PTBP1 and RBFOX RBPs coordinately drive the oncogenic splicing program active in glioblastomas demonstrating that MAPP paves the way for characterizing pre-mRNA processing regulators under physiological and pathological conditions.

A comprehensive review on role of magnetic resonance imaging in the precise measurement of corpus callosum

Magnetic Resonance Imaging (MRI) has emerged as a powerful and non-invasive imaging technique, playing a pivotal role in neuroimaging research and clinical diagnosis. This comprehensive review explores the significance of MRI in the precise measurement of the corpus callosum, a key structure connecting the two hemispheres of the brain. The corpus callosum plays a crucial role in inter hemispheric communication and is implicated in various neurological and psychiatric disorders. The review begins by elucidating the anatomy and functions of the corpus callosum, emphasizing its importance in facilitating seamless communication between the cerebral hemispheres. Subsequently, the paper delves into the historical evolution of MRI techniques and how advancements have enhanced the visualization and measurement capabilities of the corpus callosum. A detailed examination of various MRI modalities, including structural MRI, diffusion tensor imaging (DTI), and functional MRI, is presented in the context of corpus callosum analysis. Structural MRI provides high-resolution images for accurate morphological assessments, while DTI offers insights into white matter microstructure and fiber tractography, allowing for a more comprehensive understanding of the corpus callosum's integrity. The review also highlights the role of MRI in investigating alterations in the corpus callosum associated with neurological disorders such as multiple sclerosis, epilepsy, and neurodevelopmental disorders. Additionally, the paper explores how functional MRI contributes to understanding the functional connectivity and inter hemispheric interactions mediated by the corpus callosum. Challenges and limitations in the measurement of the corpus callosum using MRI are discussed, including methodological considerations, image artifacts, and potential sources of variability. The review concludes by outlining future directions in corpus callosum imaging research, including the integration of advanced imaging techniques, artificial intelligence, and large-scale multi-center studies to enhance the precision and reliability of measurements.In summary, this comprehensive review underscores the pivotal role of MRI in advancing our understanding of the corpus callosum, providing valuable insights into both normal brain function and pathological conditions. The continual evolution of MRI techniques holds promise for further refining the assessment of the corpus callosum, ultimately contributing to improved diagnostic accuracy and therapeutic interventions in neurological and psychiatric disorders.

Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models.

Antibody-drug conjugates (ADCs) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given the molecular heterogeneity of GBM, bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs, Losatuxizumab vedotin (ABBV-221) and Depatuxizumab mafodotin (Depatux-M), with similar auristatin toxins, were compared in GBM patient-derived xenografts (PDXs) and normal murine brain following direct infusion by convection enhanced delivery (CED). EGFRviii-amplified and non-amplified GBM PDXs were used to determine in vitro cytotoxicity, in vivo efficacy, and bystander activities of ABBV-221 and Depatux-M. Non-tumor bearing mice were used to evaluate pharmacokinetics and toxicity of ADCs using LC-MS/MS and immunohistochemistry. CED improved intracranial efficacy of Depatux-M and ABBV-221 in three EGFRviii-amplified GBM PDX models (Median survival: 125 to >300 days vs 20-49 days with isotype-control AB095). Both ADCs had comparable in vitro and in vivo efficacy. However, neuronal toxicity and CD68+ microglia/macrophage infiltration were significantly higher in brains infused with ABBV-221, with the cell-permeable MMAE, as compared to Depatux-M, with the cell-impermeant MMAF. CED infusion of ABBV-221 into brain or incubation of ABBV-221 with normal brain homogenate resulted in significant release of MMAE, which is consistent with linker instability in the brain microenvironment. EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intra-tumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window.

Characterizing dysregulations via cell-cell communications in Alzheimer’s brains using single-cell transcriptomes

BackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting 44 million people worldwide, leading to cognitive decline, memory loss, and significant impairment in daily functioning. The recent single-cell sequencing technology has revolutionized genetic and genomic resolution by enabling scientists to explore the diversity of gene expression patterns at the finest resolution. Most existing studies have solely focused on molecular perturbations within each cell, but cells live in microenvironments rather than in isolated entities. Here, we leveraged the large-scale and publicly available single-nucleus RNA sequencing in the human prefrontal cortex to investigate cell-to-cell communication in healthy brains and their perturbations in AD. We uniformly processed the snRNA-seq with strict QCs and labeled canonical cell types consistent with the definitions from the BRAIN Initiative Cell Census Network. From ligand and receptor gene expression, we built a high-confidence cell-to-cell communication network to investigate signaling differences between AD and healthy brains.ResultsSpecifically, we first performed broad communication pattern analyses to highlight that biologically related cell types in normal brains rely on largely overlapping signaling networks and that the AD brain exhibits the irregular inter-mixing of cell types and signaling pathways. Secondly, we performed a more focused cell-type-centric analysis and found that excitatory neurons in AD have significantly increased their communications to inhibitory neurons, while inhibitory neurons and other non-neuronal cells globally decreased theirs to all cells. Then, we delved deeper with a signaling-centric view, showing that canonical signaling pathways CSF, TGFβ, and CX3C are significantly dysregulated in their signaling to the cell type microglia/PVM and from endothelial to neuronal cells for the WNT pathway. Finally, after extracting 23 known AD risk genes, our intracellular communication analysis revealed a strong connection of extracellular ligand genes APP, APOE, and PSEN1 to intracellular AD risk genes TREM2, ABCA1, and APP in the communication from astrocytes and microglia to neurons.ConclusionsIn summary, with the novel advances in single-cell sequencing technologies, we show that cellular signaling is regulated in a cell-type-specific manner and that improper regulation of extracellular signaling genes is linked to intracellular risk genes, giving the mechanistic intra- and inter-cellular picture of AD.

Elucidating the impact of parthanatos-related microRNAs on the tumoral immune microenvironment and clinical outcome in low-grade gliomas

Parthanatos, a cell death mechanism triggered by PARP-1 activation, is implicated in oncogenic processes, yet their role in low-grade gliomas (LGG) remains poorly understood. This research investigates Parthanatos-related miRNAs' prognostic and immunomodulatory potential, alongside their influence on therapeutic outcomes in LGGs. Comprehensive miRNA and mRNA profiles of LGG patients were extracted from TCGA and CGGA databases, integrating clinical parameters to identify Parthanatos-associated miRNAs. IHC data validated the expression levels of Parthanatos-related genes in glioma versus normal brain tissues. Protein–protein interaction networks and Spearman correlation analysis facilitated the identification of key miRNAs. Parthanatos-related miRNA indices (PMI) were screened using Lasso and assessed for their accuracy in predicting prognosis, comparing their associated potential molecular functions and heterogeneity of the immune microenvironment. Drug sensitivity was assessed between different groups and optimal therapeutic agents were predicted. Validate the expression levels of key miRNAs by qPCR. Ninety-one miRNAs significantly associated with Parthanatos were screened, through which a PMI prognosis model of nine miRNAs was constructed. The PMI score was able to independently predict the prognosis of patients with LGG, and the nomogram constructed based on the PMI provided a practical tool for clinical prediction of patient prognosis. The proportion of immune response was lower in patients in the high-risk group, and there were significant differences in drug sensitivity between different risk classes, while drugs such as Fasudil were identified as the most promising therapeutic agents for patients in the high-risk group. Our findings highlight the critical role of Parthanatos-associated miRNAs in the progression and treatment of LGG, offering novel insights into their prognostic value and therapeutic potential.

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

BackgroundLncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown.MethodsThe expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay.ResultsWe demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein.ConclusionsOverall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM.Graphical LINC00606 is highly expressed in GBM patients with carcinogenic function and correlated with poor prognosis. LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B.

Discriminating Glioblastoma from Normal Brain Tissue In Vivo Using Optical Coherence Tomography and Angiography: A Texture and Microvascular Analysis Approach

Brain tumors arise from abnormal cell growth in the brain. Glioblastoma, the most common and aggressive type, poses significant challenges for identification during surgery. The primary goal of this study is to identify and differentiate normal brain tissue from glioblastoma tissue using optical coherence tomography (OCT) and OCT angiography (OCTA). These techniques offer a non-invasive way to analyze the morphological and microvascular alternations associated with glioblastoma in an animal model. To monitor the changes in morphology and vascular distribution of brain tissue as glioblastoma tumors grow, time-series OCT and OCTA results were collected for comparison. Texture analysis of OCT images was proposed using the gray-level co-occurrence matrix (GLCM), from which homogeneity and variance were calculated as discriminative parameters. Additionally, OCTA was used to assess microvascular characteristics, including vessel diameter, density, and fractal dimension. The findings demonstrate that the proposed methods can effectively distinguish between normal and cancerous brain tissue in vivo.

Comprehensively evaluating the performance of Elekta high-definition dynamic radiosurgery for hypofractionated stereotactic radiotherapy of multiple brain metastases

PurposeTo evaluate the dosimetric and delivery performance of Elekta high-definition dynamic radiosurgery (HDRS) in hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BMs) by comparison with a conventional single-isocenter noncoplanar volumetric modulated arc therapy (VMAT) technique using the RayStation treatment planning system (TPS). Materials and methodsFrom June 2022 to October 2023, thirty-two patients (a total of 140 BMs) treated with HSRT (30–48 Gy/3-6f) via HDRS-based single-isocenter noncoplanar VMAT (HDRS-VMAT) were retrospectively selected for this study. Each patient was replanned using RayStation TPS-based single-isocenter noncoplanar VMAT (RayStation-VMAT). HDRS-VMAT and RayStation-VMAT plans were compared in terms of the gradient index (GI), conformity index (CI), normal brain tissue (NBT) dose exposure, monitor units (MUs), homogeneity index (HI), delivery accuracy, and beam-on time (BOT). ResultsCompared with the RayStation-VMAT plan, the HDRS-VMAT plan achieved superior CI (1.14 ± 0.09 vs. 1.23 ± 0.12, P < 0.001) and GI (5.23 ± 1.18 vs. 7.83 ± 2.75, p < 0.001) but had greater HI values. Compared with the RyaStation-VMAT plan, the HDRS-VMAT plan also yielded significantly lower NBT dose exposures (V23Gy, V21Gy, V18Gy, V12Gy and Dmean) but at the cost of increased MUs (3659.16 ± 1225.28 vs. 2536.23 ± 785.80, p < 0.001). The difference in BOTs was minimal (<1 min), which was not considered clinically significant. Furthermore, the HDRS-VMAT exhibited a higher gamma passing rate across all criteria (P < 0.001), particularly under stricter criteria (2%/1 mm), achieving an approximately 3% increase. ConclusionCompared with RaySation-VMAT, HDRS-VMAT offers superior target conformity, better NBT sparing, and higher delivery accuracy while maintaining comparable delivery efficiency. This represents a promising approach for HSRT of multiple BMs.

Hydroxylated polychlorinated biphenyls may affect the thyroid hormone-induced brain development during metamorphosis of Xenopus laevis by disturbing the expression of matrix metalloproteinases.

Thyroid hormones are primarily responsible for the brain development in perinatal mammals. However, this process can be inhibited by external factors such as environmental chemicals. Perinatal mammals are viviparous, which makes direct fetal examination difficult. We used metamorphic amphibians, which exhibit many similarities to perinatal mammals, as an experimental system. Therefore, using metamorphic amphibians, we characterized the gene expression of matrix metalloproteinases, which play an important role in brain development. The expression of many matrix metalloproteinases (mmps) was characteristically induced during metamorphosis. We also found that the expression of many mmps was induced by T3 and markedly inhibited by hydroxylated polychlorinated biphenyls (PCBs). Overall, our findings suggest that hydroxylated PCBs disrupt normal brain development by disturbingthe gene expression of mmps.

Comparative analysis of deep learning techniques for accurate stroke detection

Background: The traditional diagnosis of strokes through computed tomography (CT) heavily relies on radiologists’ expertise for accurate interpretation. However, the increasing demand for this critical task exceeds the available radiologist workforce, necessitating innovative solutions. This research addresses this challenge by introducing deep learning techniques to enhance the initial screening of stroke cases, thereby augmenting radiologists’ diagnostic capabilities. Objective: This study aims to compare four techniques for classifying stroke lesions in CT images. Materials and methods: Four distinct models-CNN-2-Model, LeNet, GoogleNet, and VGG-16-were trained using a dataset comprising 1,636 CT images, including 1,111 normal brain images and 525 stroke images. Seventy percent of the images were used to train the most effective deep learning model, and subsequently, these images were utilized to evaluate the performance of each model. The evaluation involved assessing accuracy, precision, sensitivity, specificity, F1 score, false positive rate, and AUC. Results: The evaluation process included a comprehensive statistical analysis of the models’ prediction results. The findings revealed that VGG-16 emerged as the top-performing deep learning model, achieving an impressive accuracy of 0.969, precision of 0.952, sensitivity of 0.952, specificity of 0.978, F1 score of 0.952, false positive rate of 0.022, and AUC of 0.965. Conclusion: In conclusion, deep learning techniques, particularly the VGG-16 model, demonstrate significant promise in enhancing the accuracy of stroke lesion classification in CT images. These findings underscore the potential of leveraging advanced technologies to address the growing challenges in stroke diagnosis and pave the way for more efficient and accessible healthcare solutions.

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis.

Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLA-DRB*10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms.

Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS.

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors, many innate immune and local apoptosis related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early β-amyloid pathology. But microglia are not involved in synapse loss at late β-amyloid stages. Phagocytic microglia also engulfment synapses in complement dependent way in schizophrenia, anxiety and stress. Besides, phagocytic astrocytes engulf synapses in a MEGF10 dependent way during visual development, memory and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminating excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

Abstract PO2-19-01: A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition?

Abstract Background: Estrogen (ER) and Progesterone (PR) receptors are rich in regions of the brain involved in cognitive functions, like the hippocampus and cerebral cortex. Animal models have shown that estradiol regulates neurocognition and plays an important role in the normal brain development. Hormone positive (HR+) breast cancers (BC) comprise 70% of the disease and the standard of care in the post-menopausal group is the use of Aromatase Inhibitors (AI) for at least 5 years. While “chemo brain” is a well-recognized term, neurocognitive changes from estrogen inhibition by AI have not been clearly defined. As neurocognition is multi-faceted, information on specific aspects affected by AI use is unclear. We hope to answer this through our trial. Design: The study is a single arm, self-controlled prospective observational cohort study in which, post-menopausal BC patients who are to be started on AIs will undergo a battery of neurocognitive tests just before starting AI, at 6 months and at 12 months after being on AI. The changes at 6 and 12 months will be compared to baseline. The tests will involve objective [Hopkins verbal learning test revised (HVLT), Controlled Oral Word Association Test from Multilingual Aphasia Examination, Trial Making Test A and B, and Recall and Recognition of Word List encoded from the HVLT] and subjective/patient-reported [The Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog)] components. Tests for anxiety [Generalized Anxiety Disorder (GAD)–7], depression [Patient Health Questionnaire (PHQ)-9] and working memory (Working Memory Tasks from the Wechsler Adult Intelligence Scale) will also be assessed. While the objective tests involve providing patients with specific instructions and asking them to complete the tasks, the FACT Cog questionnaire uses a self-reported 37-item questionnaire enabling assessment of their perceived symptoms. The tests have been summarized in the table. Eligibility criteria: ER/PR+ post-menopausal BC and DCIS patients who are English speaking and are planning to start AIs will be included. Patients who have received hormonal therapy or chemotherapy in the past, those who are scheduled to receive chemotherapy, those who have undergone Whole brain Radiation therapy (RT), those with a premenopausal status, and those having comorbid conditions that could affect cognitive functioning (like any form of dementia or brain metastasis) will be excluded. Specific aims: Our aim is to see if there are progressive neurocognitive changes compared to an age-appropriate baseline and to see if changes to both objective and perceived cognitive changes occur over the course of AI use, in post-menopausal HR+ BC patients. Statistical methods: The T-test and McNemer test will be used. The normal values provided from the test may be used as a standard to justify normal or abnormal values from the collected data. Therefore, a percentage of normal (or abnormal) subjects in each time point can be derived and compared using the McNemar's test. Present accrual and target accrual: 4 patients have been accrued as of June 2023 with a target accrual of 80 patients [80% power to detect a significant change, at a p of 0.05]. Contact information for people with a specific interest in the trial: Dr Abirami Sivapiragasam (abisiva2019@yahoo.com), Dr Sam Benjamin (benjamis@upstate.edu), Dr Prashanth Ashok Kumar (ashokkup@upstate.edu), Amy Bubb (bubbam@upstate.edu). Summary of the neurocognitive tests employed in the trial. Citation Format: Prashanth Ashok Kumar, Erinn McDowell, Amy Bubb, Danning Huang, Susan Sperry, Sam Benjamin, Abirami Sivapiragasam. A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-01.