Search Results (2,594)

Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD’s antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids’ pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid’s potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid’s therapeutic potential for CDD. Full article

Background: The diagnostic accuracy for Parkinson’s disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research point of view. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein, we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with >10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen’s d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. The effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. The PD cohort characteristics (sex, age, disease duration, UPDRS, H & Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. The standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future. Full article

Background: Post-stroke epilepsy can reduce patients’ abilities to carry out various activities of daily living. Despite their importance in preventing the onset of post-stroke epilepsy, the prophylactic administration of antiepileptic drugs is controversial due to a lack of high-level clinical research. In this study, we initiated a prospective interventional study of prophylactic antiepileptic drug administration in patients with a subcortical hemorrhage, who are at the highest risk of developing epilepsy after experiencing a stroke. Methods: The study was conducted in a single-center setting and was a single-arm study with no control group; the case entry period started in November 2023 and is due to end in March 2025. Only cases with a subcortical hemorrhage will be included. The treatment regimen used in this study is 2 mg of perampanel per day. Perampanel will be administered for one year, followed by two years of follow-up, for a total study period of three years. The primary endpoint will be the development of epilepsy. Results: Perampanel administration is expected to reduce the incidence of post-stroke epilepsy in comparison to the results of previous reports on the use of alternative treatments. Conclusions: The results of this study will provide new insights into the prevention of post-stroke epilepsy. The relatively small size of this study makes it difficult to provide strong evidence of the efficacy of perampanel, but it may serve as a basis for larger clinical trials. Full article

Epilepsy remains a disease that affects many people around the world. With the development of new drugs to treat this condition, the importance of therapeutic drug monitoring continues to rise and remains a challenge for the medical community. This review article explores recent advances in the detection of antiepileptic drugs across various sample types commonly used for drug monitoring, with a focus on their applications and impact. Some of these new methods have proven to be simpler, greener, and faster, making them easier to apply in the context of therapeutic drug monitoring. Additionally, besides the classic use of blood and its derivatives, there has been significant research into the application of alternative matrices due to their ease of sample collection and capacity to reflect drug behavior in blood. These advances have contributed to increasing the efficacy of therapeutic drug monitoring while enhancing its accessibility to the population. Full article

Brain endothelial cells (ECs) are essential elements of the blood–brain barrier (BBB), maintaining its integrity through both paracellular junctions and transcellular transport systems. Myosin IIA, a multifunctional protein, plays a significant role in various cellular processes, including cytoskeletal maintenance, cell division, and signal transduction. While Myosin IIA has been implicated in bleeding and ischemic stroke, its role in regulating BBB integrity under physiological conditions remains unclear. In this study, we investigated the impact of Myosin IIA deficiency on BBB integrity using intravenous tracer injections and models of epilepsy. Flow cytometry, Western blot, and real-time PCR were employed to isolate brain cells and assess changes in protein and mRNA levels. Additionally, immunofluorescence staining and electron microscopy were used to explore alterations in protein expression and the structure of BBB. Our results demonstrate that endothelial Myosin IIA deficiency increased BBB permeability and exacerbated symptoms in BBB-related diseases. Mechanistically, we found that Myosin IIA modulates β-catenin transcription and protein interactions. The overexpression of β-catenin in brain endothelial Myosin IIA deficiency mice improved BBB integrity and reduced disease severity. This study establishes Myosin IIA as a critical regulator of BBB integrity and suggests new therapeutic targets for vascular diseases. Full article

Since genetic mutations during brain development play a significant role in the genesis of epilepsy, and such genetically determined epilepsies are the most difficult to treat, there is a need to study the mechanisms of epilepsy development with deletions of various transcription factors. We utilized heterozygous mice (Sip1^wt/fl) with a neuronal deletion of the transcription factor Sip1 (Smad interacting protein 1) in the cerebral cortex. These mice are characterized by cognitive impairment and are prone to epilepsy. It is known that the brain-derived neurotrophic factor (BDNF) has a neuroprotective effect in various neurodegenerative diseases. Therefore, we created and applied an adeno-associated construct carrying the BDNF sequence selectively in neurons. Using in vitro and in vivo research models, we were able to identify a key gen, the disruption of whose expression accompanies the deletion of Sip1 and contributes to hyperexcitation of neurons in the cerebral cortex. Overexpression of BDNF in cortical neurons eliminated epileptiform activity in neurons obtained from heterozygous Sip1 mice in a magnesium-free model of epileptiform activity (in vitro). Using PCR analysis, it was possible to identify correlations in the expression profile of genes encoding key proteins responsible for neurotransmission and neuronal survival. The effects of BDNF overexpression on the expression profiles of these genes were also revealed. Using BDNF overexpression in cortical neurons of heterozygous Sip1 mice, it was possible to achieve 100% survival in the pilocarpine model of epilepsy. At the level of gene expression in the cerebral cortex, patterns were established that may be involved in the protection of brain cells from epileptic seizures and the restoration of cognitive functions in mice with Sip1 deletion. Full article

Background/Objectives: Although the involvement of progressive brain alterations in epilepsy was recently suggested, individual patients’ trajectories of white matter (WM) disruption are not known. Methods: We investigated the disease progression patterns of WM damage and its associations with clinical metrics. We examined the cross-sectional diffusion tensor imaging (DTI) data of 155 patients with unilateral temporal lobe epilepsy (TLE) and 270 age/gender-matched healthy controls, and we then calculated the average fractional anisotropy (FA) values within 20 WM tracts of the whole brain. We used the Subtype and Stage Inference (SuStaIn) program to detect the progression trajectory of FA changes and investigated its association with clinical parameters including onset age, disease duration, drug-responsiveness, and the number of anti-seizure medications (ASMs). Results: The SuStaIn algorithm identified a single subtype model in which the initial damage occurs in the ipsilateral uncinate fasciculus (UF), followed by damage in the forceps, superior longitudinal fasciculus (SLF), and anterior thalamic radiation (ATR). This pattern was replicated when analyzing TLE with hippocampal sclerosis (n = 50) and TLE with no lesions (n = 105) separately. Further-progressed stages were associated with longer disease duration (p < 0.001) and a greater number of ASMs (p = 0.001). Conclusions: the disease progression model based on WM tracts may be useful as a novel individual-level biomarker. Full article

Electroencephalography (EEG) helps to assess the electrical activities of the brain so that the neuronal activities of the brain are captured effectively. EEG is used to analyze many neurological disorders, as it serves as a low-cost equipment. To diagnose and treat every neurological disorder, lengthy EEG signals are needed, and different machine learning and deep learning techniques have been developed so that the EEG signals could be classified automatically. In this work, five ensemble models are proposed for EEG signal classification, and the main neurological disorder analyzed in this paper is epilepsy. The first proposed ensemble technique utilizes an equidistant assessment and ranking determination mode with the proposed Enhance the Sum of Connection and Distance (ESCD)-based feature selection technique for the classification of EEG signals; the second proposed ensemble technique utilizes the concept of Infinite Independent Component Analysis (I-ICA) and multiple classifiers with majority voting concept; the third proposed ensemble technique utilizes the concept of Genetic Algorithm (GA)-based feature selection technique and bagging Support Vector Machine (SVM)-based classification model. The fourth proposed ensemble technique utilizes the concept of Hilbert Huang Transform (HHT) and multiple classifiers with GA-based multiparameter optimization, and the fifth proposed ensemble technique utilizes the concept of Factor analysis with Ensemble layer K nearest neighbor (KNN) classifier. The best results are obtained when the Ensemble hybrid model using the equidistant assessment and ranking determination method with the proposed ESCD-based feature selection technique and Support Vector Machine (SVM) classifier is utilized, achieving a classification accuracy of 89.98%. Full article

Epilepsy is a critical neurological condition characterized by the disturbance of the excitatory neuron network, resulting in recurrent seizures. It is a serious health problem requiring intensive attention. The present study was designed to use bibliometric analysis to assess scientific research output on pharmacogenetics in epilepsy and drug-resistant epilepsy in Morocco during 1969–2024. The main objective of this study was to analyze scientific production and research development and to introduce available solutions to manage the elevating burden of epilepsy. The strategy approach comprised a suitable search scheme to collect publications related to epilepsy using the Scopus database. All the documents retrieved were analyzed to determine several parameters, including the number of publications annually, type of documents, institution and author productivity, and relevant sources. Studies on pharmacogenetics and drug-resistant epilepsy in Morocco are limited. The findings revealed that the number of articles has increased during the last decade. Publications remain scarce, especially on pharmacogenetics and drug-resistant epilepsy, and the most widely available publications include articles on epilepsy, seizures, mental illness, and anticonvulsant agents. Based on the search strategy, a bibliometric analysis identified potential subjects for further study. Consequently, research on epilepsy is essential to fully understand the condition, but it remains insufficient, and further studies are required, particularly on the pharmacogenetics of epilepsy. Full article

Background: Antiseizure medications (ASMs) are crucial for managing epilepsy in children. However, a well-documented side effect of ASMs is their impact on bone health, often due to interference with vitamin D metabolism. This can lead to vitamin D deficiency in children with epilepsy. This study aimed to determine if a daily dose of 400 IU or 1000 IU would maintain adequate vitamin D levels in children with epilepsy. Methods: A phase IV randomized controlled trial enrolled children aged 2–16 years with epilepsy and receiving antiseizure medications. Children were divided into two groups: the monotherapy group, which was defined as children on one antiseizure medication (ASM), and the polytherapy group, which was defined as children receiving two or more ASMs. Eligible children with levels above 75 nmol/L were randomized to receive a maintenance dose of either 400 IU/day or 1000 IU/day of cholecalciferol. Baseline and 6-month assessments included demographic data, anthropometric measurements, seizure type, medications, seizure control, and 25(OH)D level. Results: Out of 163 children, 90 were on monotherapy and 25 on polytherapy. After 6 months of vitamin D maintenance, the proportion of children with 25(OH)D concentration below 75 nmol/L was 75.0% in the 400 IU group and 54.8% in the 1000 IU group. In the monotherapy group, baseline seizure-free children increased from 69% to 83.6% after treating vitamin D deficiency. Conclusion: Daily vitamin D supplementation with 1000 IU may be beneficial for children with epilepsy, particularly those receiving monotherapy, to maintain sufficiency and potentially improve seizure control. Full article

Background: Mental health issues are increasingly prominent worldwide, posing significant threats to patients and deeply affecting their families and social relationships. Traditional diagnostic methods are subjective and delayed, indicating the need for an objective and effective early diagnosis method. Methods: To this end, this paper proposes a lightweight detection method for multi-mental disorders with fewer data sources, aiming to improve diagnostic procedures and enable early patient detection. First, the proposed method takes Electroencephalography (EEG) signals as sources, acquires brain rhythms through Discrete Wavelet Decomposition (DWT), and extracts their approximate entropy, fuzzy entropy, permutation entropy, and sample entropy to establish the entropy-based matrix. Then, six kinds of conventional machine learning classifiers, including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naive Bayes (NB), Generalized Additive Model (GAM), Linear Discriminant Analysis (LDA), and Decision Tree (DT), are adopted for the entropy-based matrix to achieve the detection task. Their performances are assessed by accuracy, sensitivity, specificity, and F1-score. Concerning these experiments, three public datasets of schizophrenia, epilepsy, and depression are utilized for method validation. Results: The analysis of the results from these datasets identifies the representative single-channel signals (schizophrenia: O1, epilepsy: F3, depression: O2), satisfying classification accuracies (88.10%, 75.47%, and 89.92%, respectively) with minimal input. Conclusions: Such performances are impressive when considering fewer data sources as a concern, which also improves the interpretability of the entropy features in EEG, providing a reliable detection approach for multi-mental disorders and advancing insights into their underlying mechanisms and pathological states. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists such as liraglutide are known for their neuroprotective effects in neurodegenerative disorders, but their role in temporal lobe epilepsy (TLE) remains unclear. We aimed to investigate the effects of liraglutide on several biological processes, including inflammation, antioxidant defense mechanisms, mitochondrial dynamics, and function, as well as cognitive and behavioral changes in the TLE model. Methods: Low-dose, repeated intraperitoneal injections of lithium chloride–pilocarpine hydrochloride were used to induce status epilepticus (SE) in order to develop TLE in rats. Fifty-six male Sprague Dawley rats were subjected and allocated to the groups. The effects of liraglutide on inflammatory markers (NLRP3, Caspase-1, and IL-1β), antioxidant pathways (Nrf-2 and p-Nrf-2), and mitochondrial dynamics proteins (Pink1, Mfn2, and Drp1) were evaluated in hippocampal tissues via a Western blot. Mitochondrial function in peripheral blood mononuclear cells (PBMCs) was examined using flow cytometry. Cognitive-behavioral outcomes were assessed using the open-field, elevated plus maze, and Morris water maze tests. Results: Our results showed that liraglutide modulates NLRP3-mediated inflammation, reduces oxidative stress, and triggers antioxidative pathways through Nrf2 in SE-induced rats. Moreover, liraglutide treatment restored Pink1, Mfn2, and Drp1 levels in SE-induced rats. Liraglutide treatment also altered the mitochondrial function of PBMCs in both healthy and epileptic rats. This suggests that treatment can modulate mitochondrial dynamics and functions in the brain and periphery. Furthermore, in the behavioral aspect, liraglutide reversed the movement-enhancing effect of epilepsy. Conclusions: This research underscores the potential of GLP-1RAs as a possibly promising therapeutic strategy for TLE. Full article

Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota–gut–brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut–brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer’s disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer’s neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson–Konovalov disease (WD), multisystem atrophy (MSA), Huntington’s chorea (HC), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut–brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases. Full article

Objectives: To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging (“MRI-negative” or “non-lesional MRI”). Methods: We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities. Results: We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32–100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52–89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28–75% of cases and altered the surgical plan in 5–33% of cases. Conclusions: MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy. Full article

Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant. CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest. This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed. The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD). Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut. Full article