To discover novel multi-functional antiepileptic agents, nipecotamide was hybridized with salicylaldehyde, paeonol, vanillin and cinnamaldehyde to generate a series of N-substituted nipecotamide derivatives. Biological screening revealed that compound 11c exhibited remarkable scavenging activities against ABTS (2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulfonic acid)) radical (scavenging IC50: 92.0 μM), DPPH (1,1-Diphenyl-2-picrylhydrazyl) radical (scavenging IC50: 70.9 μM), and superoxide anion radical (inhibition percentage: 48.4 %). Additionally, electrophysiological results showed that compound 11c demonstrated potent inhibitory effects on abnormal electrical discharges. Furthermore, compound 11c displayed the capacity to relieve H2O2-induced oxidative damage and LPS-induced neuroinflammation at the cellular level. Besides, compound 11c could cross the blood-brain barrier, alleviate the symptoms of epilepsy induced by pentylenetetrazole and pilocarpine effectively, and mitigate oxidative damage caused by sodium nitrite in mice. Therefore, compound 11c possesses symptomatic-treatment and disease-modification properties for epilepsy. These results highlighted that compound 11c was a highly promising candidate for further development as an antiepileptic agent.

Oxidative stress (OS) resulting from high levels of free radicals contributes to the initiation and progression of epilepsy. Temporal lobe epilepsy (TLE) is associated with alteration in the structure and function of the hippocampus and is modeled in mice using kainic acid (KA). In this study, the neuroprotective effect of ellagic acid (EA) on KA-induced epilepsy in mice was evaluated. Sixty male Swiss albino mice were assigned to six groups: I received normal saline (NS; 10 ml/kg, intraperitoneally (i.p.)); II, received KA (15 mg/kg, i.p.); III, received diazepam (20 mg/kg, i.p.) and KA (15 mg/kg, i.p.); IV-VI, received EA (10, 20 and 40 mg/kg, i.p.), and KA (15 mg/kg, i.p.). Treatments were done 30 min before KA injection. Seizure (latency, duration, activity) and mortality were monitored for 2 h post-injection. OS was evaluated by measuring MDA, NO, and GSH levels and CAT, SOD, and GPx activities. Levels of TNF-α in the brain tissue were measured. Furthermore, a histological examination of the hippocampus was carried out. RESULTS: showed that EA pretreatment caused a decline in seizure activity score and duration compared to the KA-treated group. EA pretreatment reduced mortality in KA-treated mice. EA suppressed the generation of MDA and NO; whereas it preserved GSH and the activity of GPx, SOD, and CAT. Additionally, EA exerted anti-inflammatory effects by reducing TNF-α level. Histopathologically, EA reduced KA-induced neuronal damage. EA demonstrated protective effects against KA-related epilepsy and brain damage. Due to its anti-inflammatory and radical scavenging properties, EA may be considered a potential therapeutic option in epilepsy.

To explore the functions and potential regulatory mechanisms of chemokine and chemokine receptor (CCR)-related genes in epilepsy.

CCRs were identified as candidate genes and their causal relationship with epilepsy was rigorously evaluated via Mendelian randomization analysis. Subsequently, single-cell RNA sequencing (scRNA-seq) data were analyzed to identify and classify cell clusters into distinct types based on cellular annotation. Differential expression analysis was conducted to pinpoint key genes by overlapping the candidate gene set with differentially expressed genes (DEGs). Furthermore, potential therapeutic drugs for epilepsy were predicted, offering novel avenues for disease management and treatment.

In total, 6395 DEGs were identified across the six cell clusters. After their intersection, CCRL2, XCL2, CXCR5, CXCL1, and CX3CR1 were pinpointed as key genes. Microglia, T cells, B cells, and macrophages have been emerged as critical cells. Furthermore, CXCL1 was regulated by hsa-miR-570-3p and hsa-miR-532-5p. Notably, CXCR5, CXCL1, and CX3CR1 were associated with 27 drug compounds. This comprehensive study leveraged scRNA-seq and transcriptomic data to elucidate the roles of CCR-related genes in epilepsy. Notably, CCRL2, XCL2, CXCR5, CXCL1,and CX3CR1 were identified as key genes implicated in epilepsy, whereas microglia, T cells, B cells, and macrophages were recognized as critical contributors to the development of epilepsy.

Regulating the expression of CCRL2, XCL2, CXCR5, CXCL1, and CX3CR1, along with the activity of these immune cells may offer therapeutic potential for the alleviation of epilepsy.

Epilepsy is often marked by paroxysmal seizures that disrupt the brain's sensory, motor, and psychosocial functions. The underlying pathology is generally believed to involve an imbalance between excitatory and inhibitory neurotransmission. However, a less explored but significant contributor to epilepsy is the collapse of the brain's metabolic and bioenergetic systems. The breakdown of the brain's bioenergetic system leads to the activation of various detrimental downstream signaling cascades that ultimately result in oxidative stress, neuroinflammation, and reduced autophagic flux, all of which impair neuronal-glial communication and precipitate epileptic attacks. This highlights the pressing need for a therapeutic agent to address these complex challenges. Researchers have identified adenosine monophosphate kinase (AMPK) as a potential solution. AMPK acts as the body's primary stress sensor, activated in response to the deficiency of growth factors and nutrient starvation to restore energy homeostasis. AMPK activation also maintains the intricate communication between neurons and glial cells, preserving synaptic plasticity integrity, mitigating mitochondrial damage, and dampening inflammatory signaling cascades. Despite demonstrating significant efficacy in managing a range of peripheral and neurological disorders, the role of AMPK in neurotransmission and epilepsy remains unexplored. This review explores the multifaceted molecular roles of AMPK beyond its traditional metabolic regulatory functions, suggesting that targeting AMPK could provide a novel avenue for drug development in epilepsy treatment.

Epilepsy is one of the most common and severe chronic brain diseases, affecting up to 70 million people worldwide. Neuroinflammation plays a central role in the progression of the disease. The Nod-Like Receptor Protein 6 (NLRP6) inflammasome assembles with apoptosis-associated speck-like protein (ASC) to cleave pro-caspase-1 into caspase-1, thus forming the NLRP6 inflammasome. This process promotes the maturation and release of downstream interleukins (IL)-18 and IL-1β, exacerbating pathological processes in various diseases. In this study, we demonstrated significantly enhanced NLRP6 expression in the cortex and hippocampus of epileptic mice, suggesting a role for the inflammasome in epilepsy. Immunofluorescence staining further revealed that NLRP6 was predominantly expressed in hippocampal neurons of these mice. Additionally, knockdown of NLRP6 reduced susceptibility to epilepsy, alleviated post-seizure neuronal damage, and decreased levels of pro-inflammatory cytokines, including IL-18, IL-1β, and IL-6. Conversely, NLRP6 overexpression produced opposite effects, which were effectively reversed by treatment with the caspase-1 inhibitor VX765. To the best of our knowledge, this is the first study to demonstrate a link between NLRP6 and the activation of the caspase-1/IL-1β/IL-18 signaling pathway in a kainic acid (KA)-induced epilepsy mouse model. Administration of VX765 alleviated pathological alterations and exerted neuroprotective effects. These findings suggest that NLRP6 plays a critical role in the initiation and progression of epilepsy.

Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASySs). Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated.

This retrospective cohort study evaluated incidence and risk factors for ASyS during CAR T-cell therapy. We included patients treated at Mayo Clinic in Minnesota, Florida, and Arizona who underwent CAR T-cell therapy for hematologic malignancies from October 2019 to November 2023. Pretreatment demographics, clinical information, type of CAR T-cell therapy, neuroimaging, laboratories during treatment, and clinical features during admission were analyzed. Data on treatment and prevalence of seizures, EEG, and survival at the last follow-up were assessed. T-tests and nonparametric testing were performed on categorical and continuous data, respectively. Multivariable analysis was also performed.

We included 180 patients (mean age 62.3 years, 57.2% women) with 8 (4.4%) developing ASyS at a mean of 8.0 ± 5.3 days after therapy. Earlier onset of cytotoxic release syndrome (odds ratio [OR] 1.81, 95% CI 0.62-2.99, p = 0.007), higher grade immune effector cell-associated neurotoxicity syndrome (ICANS) (OR -1.43, 95% CI -1.86 to -1.00, p < 0.001), focal neurologic deficits (OR 7.15, 95% CI 1.60-32.14, p = 0.007), and cefepime (OR 0.58, 95% CI 0.51-0.65, p = 0.022) exposure were significantly associated with a higher risk of ASyS. A multivariable model accounting for age and sex fit best using the lowest minimum immune effector cell encephalopathy score and highest ICANS grade (R2 = 0.555, χ2 = 28.507, p < 0.001). ASyS was associated with death at the last follow-up (OR 0.48, 95% CI 0.41-0.56, p = 0.007), although short-term outcomes were not affected by ASyS. Nonprotocolized antiseizure medication (ASM) prophylaxis did not affect ASyS incidence.

This study suggests a low risk of ASyS because of CAR T-cell therapy, with certain risk factors that may be predictive of ASyS and lack of a definitive and direct association of ASyS with outcomes. The current approach to ASM prophylaxis should be reconsidered when ICANS is encountered. This study is limited by its retrospective nature and the use of ASM prophylaxis in all patients with ICANS, which requires further study to assess its necessity.

Millions of people worldwide suffer from epilepsy, a persistent neurological illness characterized by recurring seizures. Despite advances in anti-epileptic medications, a significant number of patients continue to have insufficient seizure control and have side effects. Nanotechnology has emerged as a promising alternative for increasing medicine delivery and therapeutic effects in recent years. The anti-epileptic potential of nanoparticles produced from herbal medicines such as berberine-loaded zein/hyaluronic acid composite, Cannabis sativa extract-loaded nanoliposomes and nanostructured lipids, nanostructured lipid vehicle-carried safranal, and cryptolepine solid-lipid NPs is reviewed in this work, which makes use of the synergistic effects of nanotechnology and natural substances. The manuscript presents an overview of the mechanisms underlying the anti-epileptic effects of these nanoparticles, ranging from regulating neurotransmitter systems and ion channels to lowering oxidative stress and inflammation. Preclinical studies using animal models of epilepsy have shown that herbal medicine nanoparticles can reduce seizure activity, prolong seizure latency, and improve cognitive function. The findings presented in this manuscript highlight the remarkable potential of herbal medicine nanoparticles as a novel approach to the management of epilepsy. Continued research and development in this field have the potential to revolutionize epilepsy therapy and improve the quality of life for people suffering from this debilitating condition.

BID-Ozo, a mitochondrial-targeted fluorescence probe to detect endogenous ozone (O3) was developed. A significant increase in intracellular O3 was observed in PC12 cells stimulated with high concentrations of glutamate (Glu), which is used to model epilepsy.

Epilepsy is a complex neurological disorder characterized by recurrent seizures affecting millions of people worldwide. Despite advances in drug therapy, a significant proportion of patients remain resistant to conventional antiepileptic drugs (AEDs) due to challenges such as impermeability of the blood-brain barrier (BBB), multidrug resistance, and multifaceted epileptogenesis. Nanotechnology offers promising strategies to overcome these barriers by enhancing drug delivery across the BBB, improving target specificity and minimizing systemic side effects. This review explores recent advances in different innovative strategies of nanodelivery systems for epilepsy therapy, and we will discuss the design principles, mechanisms of action and therapeutic efficacy of these nanodelivery systems. In addition, we discuss the challenges and limitations that hinder the clinical translation of nanomedicine-based therapies for epilepsy. We emphasize the need for personalized and multidisciplinary approaches as well as the importance of continued research and interdisciplinary collaboration in order to translate these innovative strategies into effective therapies. Ultimately, the use of nanotechnology has the potential to enhance seizure control, reduce the burden of epilepsy, and improve the quality of life of patients affected by this complex neurological disorder. Nanotechnology-based drug delivery systems may usher in a new era of precision medicine for epilepsy treatment.

Seizures in the context of brain tumors are a relatively common symptom, with higher occurrence rates observed in glioneuronal tumors and gliomas. It is a serious burden that can have a significant impact on the quality of life (QoL) of patients and influence the disease's prognosis. Brain tumor‑related epilepsy (BTRE) is a challenging entity because the pathophysiological mechanisms are not fully understood yet. Nonetheless, neuroinflammation is considered to play a pivotal role. Next to neuroinflammation, findings on the pathogenesis of BTRE have established that certain genetic mutations are involved, of which the most known would be IDH mutations in gliomas. Others discussed more thoroughly in the present review include genes such as PTEN, TP53, IGSF3, and these findings all provide fresh and fascinating insights into the pathogenesis of BTRE. Treatment for BTRE presents unique challenges, mainly related to burdens of polytherapy, debated necessity of anti‑epileptic prophylaxis, and overall impact on the QoL. In fact, there are no established anti‑seizure medications (ASMs) of choice for BTRE, nor is there any protocol to guide the use of these medications at every step of disease progression. Treatment strategies aimed at the tumor, that is surgical procedures, radio‑ and chemotherapy appear to influence seizure control. Conversely, some ASMs have also shown antitumor properties. The present review summarizes and retrospectively analyzes the literature on the pathogenesis and management of BTRE to provide an updated comprehensive understanding. Furthermore, the challenges and opportunities for developing future therapies aimed at BTRE are discussed.

Numerous epidemiological and pathophysiological arguments suggest a bidirectional link between late-onset epilepsy and Alzheimer's disease. However, the temporal and causal relationship between the pathophysiological processes underlying these two conditions remains unclear. It is likely that these connections are complex, requiring consideration of various scenarios of causality and reciprocity. In the absence of targeted therapies that effectively address the progression of both diseases, specific measures can be taken to improve patient care. These include screening for cognitive disorders in patients with late-onset epilepsy, detecting subclinical EEG activity in patients with Alzheimer's disease, and identifying and managing cardiovascular risk factors in both populations. Looking ahead, it is evident that global population aging and the potential demographic surge in these two patient groups will necessitate greater efforts to raise awareness and enhance the training of physicians and healthcare professionals in the emerging field of "epileptogeriatrics".

Disease-modifying treatments with anti-epileptic effects are currently unavailable and urgently required for temporal lobe epilepsy (TLE). Combined therapy targeting multiple mechanisms may offer a promising anti-epileptic strategy, given the complex processes underlying epileptogenesis.

This study evaluates the effects of Edaravone Dexbroneol, a combination of Edaravone and Dexborneol in 4:1, on rat and mouse TLE models and an in vitro epileptiform activity model.

The Pilocarpine-induced rat TLE model and the Kainic acid-induced mouse TLE model were used to assess the in vivo effect of Edaravone and/or Dexbornel. Primary neurons were utilized to evaluate the in vitro effect of drugs using calcium imaging, electrophysiological and biochemical analyses, as well as RNA sequencing.

Treatment of Edaravone Dexbornel during the latent period significantly alleviated epileptic seizures in rodents, mitigated cognitive impairment, and inhibited neuronal loss and astrocytic activation. In vitro, Edaravone Dexborneol inhibited the action potentials and protected primary hippocampal neurons from Mg2+-free-induced neurite injury. All these effects were significantly more pronounced in the group treated with the Edaravone Dexborneol mixture compared to either drug used individually. Furthermore, Edaravone can significantly inhibit Mg2+-free-induced calcium oscillations in primary neurons, probably by promoting the deactivation of NMDA receptors. RNA sequencing and RT-PCR analysis revealed that synergetic regulation of lipid metabolism, oxidative stress, apoptosis, and calcium signaling probably underlay the neuroprotective effect of Edaravone Dexbornel on epileptic neurons.

Edaravone Dexborneol exhibits antiepileptic effects and may fill the gap in disease-modifying treatments for TLE.

Epilepsy is a brain disorder characterized by alterations in the neuronal environment that predispose individuals to spontaneous and recurrent epileptic seizures. One of the major challenges in recent years has been the accurate diagnosis and appropriate pharmacological management of the condition. When seizures are not well controlled, individuals may develop status epilepticus, a condition with an unfavorable prognosis that requires immediate attention and treatment. Furthermore, approximately 30 % of patients are refractory to conventional treatments. In this study, we evaluated the effects of prednisolone in an acute animal model of epileptic seizures induced by pentylenetetrazole (PTZ) at doses of 1 mg/kg and 5 mg/kg. We analyzed the severity of epileptic seizures and the modulation of pro-inflammatory cytokines in treated animals. Four treatment groups were used: saline solution, diazepam (2 mg/kg), prednisolone (1 mg/kg), and prednisolone (5 mg/kg). The animals were treated, and after 30 min, PTZ (60 mg/kg) was administered. Levels of the cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus and prefrontal cortex. Animals treated with prednisolone exhibited less severe epileptic seizures compared to the saline group, along with reduced levels of pro-inflammatory cytokines, particularly in the prefrontal cortex. Some animals were also assessed using EEG. Consistent with our previous studies, prednisolone demonstrated an anticonvulsant effect at doses of 1 mg/kg and 5 mg/kg in the acute PTZ-induced seizure model.

Epilepsy is a common and severe neurological disease characterized by spontaneous and recurrent seizures. Although anti-seizure treatments are effective for most patients, approximately 30% remain pharmacoresistant. Moreover, uncontrolled seizures are associated with increased health risks and shortened life expectancy in individuals with refractory epilepsy. Preclinical studies play a crucial role in drug discovery, and the zebrafish (Danio rerio) have been successfully employed for this purpose. In this study, we utilized the zebrafish PTZ-induced seizure model to evaluate the effects of two peptides on seizure responses: Tripeptide (p-BTX-I) and the CX2 (a Cx43derivated peptide). Zebrafish larvae at 6 days post-fertilization were pre-treated with these peptides at various concentrations, depending on their experimental groups, 24h prior to seizure induction. We assessed seizure frequency, quantified swimming activity, measured transcript levels of genes related to inflammation and apoptosis (il1b, tnfa, cox1, cox2a, il6, casp3a, casp9, baxa, bcl2a, and c-fos), and analyzed the biodistribution of both peptides. Our results indicate that the Tripeptide exhibited anti-inflammatory and anti-apoptotic effects, particularly through reducing the expression of il1b and casp9. CX2 pre-treatment significantly downregulated inflammatory markers (il1b, il6, tnfa, and cox1). Biodistribution analysis confirmed that the CX2 peptide reached the zebrafish brain, suggesting a direct role in modulating seizure-related pathways. Our findings demonstrate that Tripeptide and CX2 peptides can modulate gene expression and mitigate molecular response associated with epileptic seizures in the zebrafish brain. These peptides thus represent promising candidates for future research aimed at developing novel anti-epileptic therapies. However, additional studies are required to evaluate their long-term efficacy, elucidate underlying mechanisms of action, and explore potential translational applications.

Epilepsy is a complex neurological disorder characterized by recurrent seizures, which are driven by multifaceted pathophysiological mechanisms, including oxidative stress and neuroinflammation. Despite advancements in anti-seizure medications (ASMs), a significant proportion of patients remain resistant to treatment, highlighting the need for novel therapeutic strategies. This review focuses on the Kelch-like ECH-associated protein 1 (Keap1) / Nuclear factor erythroid 2-related factor 2 (Nrf2) / Antioxidant Response Element (ARE) / Heme Oxygenase-1 (HO-1) axis as a promising target for neuroprotection in epilepsy. We explored the intricate interactions between Keap1 and Nrf2 under homeostatic conditions and how oxidative stress disrupts this balance, triggering Nrf2 activation. This review details the subsequent process of Nrf2 nuclear translocation, its binding to AREs, and the induction of cytoprotective gene expression, which collectively orchestrate a robust cellular defense response. Special emphasis is placed on HO-1, a key effector of Nrf2-mediated neuroprotection, highlighting its enzymatic function and protective mechanisms, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Additionally, the review examines HO-1's role in mitigating seizure-induced neuronal damage. However, challenges remain, including variability in therapeutic responses, gaps in long-term clinical validation, and the need for standardized protocols. Future research should focus on biomarkers for personalized treatment, advanced imaging, and genetic tools to explore the Keap1/Nrf2/ARE/HO-1 axis in greater depth. Future studies should focus on overcoming the challenges of translating preclinical findings into clinical applications and exploring the long-term effects of targeting this pathway in epilepsy treatment.

Pericytes in the central nervous system are essential for maintaining blood-brain barrier function, regulating blood flow, modulating immune responses, and interacting closely with surrounding cells of the neurovascular unit to support brain homeostasis. Increasing evidence has highlighted their involvement in age-related neuroinflammation, where their dysfunction may contribute to sustained inflammatory states associated with neurodegenerative disorders. Here, we compared inflammatory responses to lipopolysaccharide (LPS) in primary cerebral pericytes from neonatal and adult mice and adult humans. Our findings indicate that neonatal mouse pericytes display heightened inflammatory activation, with elevated levels of ICAM-1 and several cytokines, compared to adult mouse pericytes reflecting a more reactive phenotype. In contrast, adult mouse pericytes exhibited a significantly reduced cytokine release profile, suggesting lower responsiveness. Notably, while cytokine secretion patterns in adult human pericytes, in part, mirrored those in neonatal mouse pericytes, nitric oxide production, which was observed in mouse pericytes, was absent in the human cells. These results underscore species- and age-dependent variations in cellular behavior, emphasizing the importance of utilizing human brain cell systems when conducting research on neuroinflammation. Understanding these distinctions is vital for designing accurate studies and developing targeted therapies for neuroinflammatory conditions.

The potential therapeutic value of cynarin, a phenolic compound derived from artichoke, in treating epilepsy has not yet been reported. The present study evaluated the effects of cynarin on a kainic acid (KA)-induced seizure rat model and its potential mechanism. Cynarin was administered through oral gavage at a dosage of 10 mg kg-1 daily for 7 days before the induction of seizures with KA (15 mg kg-1) via intraperitoneal injection. The results showed that pretreatment with cynarin effectively attenuated the KA-induced seizure score and electroencephalogram (EEG) changes and prevented neuronal loss and glial cell activation in the hippocampi of KA-treated rats. In addition, pretreatment with cynarin dramatically prevented the aberrant levels of high mobility group box 1 (HMGB1), toll-like receptor-4 (TLR4), p-IκB, p65-NFκB, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) induced by KA administration in hippocampal tissues. Additionally, KA substantially increased hippocampal glutamate levels and decreased cerebral blood flow, which were significantly alleviated by pretreatment with cynarin. The observed effects of cynarin were comparable to those of the antiepileptic drug carbamazepine (CBZ). Furthermore, there was no significant difference in the serum AST, ALT, creatinine, or bilirubin levels between the cynarin-treated rats and the control rats. Cynarin has a neuroprotective effect on a rat model of seizures induced by KA, reducing seizures, gliosis, inflammatory cytokines, and glutamate elevation and increasing cerebral blood flow. Thus, cynarin has therapeutic potential for preventing epilepsy.

The objective of this study is to systematically review the clinical studies investigating the use of steroids in adult epilepsy.

This systematic review utilized Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) to examine literature on the use of steroids in adult epilepsy. Three databases, Embase, PubMed and Medline, were searched and clinical studies fitting the inclusion and exclusion criteria were included for review.

There were 4333 articles retrieved after duplicates were removed and 16 met the inclusion criteria. Three of these studied corticosteroid use in seronegative autoimmune epilepsies. There was one study that examined the use of corticosteroids in adult-onset Rasmussen's Encephalitis. There were three studies which described the use of neurosteroids in various forms of adult epilepsy. The remaining 9 studies were pertaining to the use of corticosteroids in refractory status epilepticus.

Steroids show favorable outcomes in many forms of adult epilepsy. Yet, there is a paucity of data supporting implementation of this treatment in practice. High-level evidence such as Randomized-Controlled Trials investigating the use of corticosteroids in adult epilepsy are required, particularly those examining seronegative autoimmune epilepsy and refractory status epilepticus given the prevalence of these conditions and lack of treatment options.

Epilepsy, characterized by repeated seizures often without a known cause, is initially treated with anti-seizure medications. However, about one third of patients do not become seizure-free with medication. Steroids, known for their anti-inflammatory effect, are now being trialed as a seizure treatment for difficult to control seizures because uncontrolled seizures are thought to cause inflammation in the brain. However, the use of steroids as a treatment for uncontrolled seizures has not been researched widely. This article reviews studies exploring the use of steroids in adult epilepsy and finds that there is some evidence that steroids may be able to improve seizures in some cases. Yet, further research is needed to better understand the effect and benefits of steroids in managing epilepsy.

Tuberous sclerosis complex (TSC) is a monogenetic disorder associated with sustained mechanistic target of rapamycin (mTOR) activation, leading to heterogeneous clinical manifestations. Epilepsy and renal angiomyolipoma are the most important causes of morbidity in adult people with TSC (pwTSC). mTOR is a key player in inflammation, which in turn could influence TSC-related clinical manifestations. Reliable biomarkers are lacking to monitor and predict evolution and response to treatment for epilepsy in pwTSC. Inflammation has been implicated in epileptogenesis in non-TSC-related epilepsy. We aimed to characterize the relation between markers of neuroglial activation/injury, markers of peripheral inflammation, and active epilepsy in pwTSC to identify accessible biomarkers and potential new therapeutic targets.

We performed a cross-sectional study to investigate markers of central nervous system (CNS) (neurofilament light [NfL] and glial fibrillary acidic protein [GFAP]) and peripheral (45 cytokines) inflammation in the peripheral blood of pwTSC (n = 46) vs age- and sex-matched healthy controls (HCs) (n = 26). In pwTSC, markers associated with active epilepsy (n = 23/46) were compared to non-TSC epilepsy controls (n = 18). Observations on markers of neuroglial activation/injury (GFAP, NfL) were confirmed in an independent TSC cohort (n = 45; 69% with active epilepsy).

We report that TSC is characterized by elevated serum levels of marker of astrogliosis (GFAP), pro-inflammatory molecules (interleukin 1β [IL-1β], CXCL8) and trophic factor (epidermal growth factor [EGF]) compared to HCs and to non-TSC-related epilepsy controls. Among pwTSC, renal angiomyolipoma presence and size was associated with IL-15. It is notable that active epilepsy in pwTSC was associated with higher levels of GFAP compared to pwTSC without epilepsy, which was confirmed in an external validation cohort, and with elevated levels of pro-inflammatory cytokines (IL-17A, IL-17C, tumor necrosis factor α [TNF-α]), not significantly related to seizure activity or treatment with mTOR inhibitor. These associations remained significant after adjusting for age and sex.

These results suggest that key inflammatory mediators could contribute to epileptogenesis and represent novel biomarkers and therapeutic targets in TSC.

Neurological diseases present a wide range of conditions, intricate diagnosis and treatment processes, and complex prognostic considerations. Therefore, research focusing on the diagnosis and treatment of these diseases is crucial. Exosomal miRNAs are small RNA molecules enclosed in membrane vesicles, released by cells and known to play roles in the development of various neurological disorders. They also serve as specific biomarkers for these conditions. Drawing on extensive research on exosomal miRNAs in diseases like stroke, Alzheimer's, epilepsy, Parkinson's, and neuroregeneration, this paper provides a comprehensive review of the relationship between exosomal miRNAs and neurological diseases. We strive to offer current and detailed theoretical understandings to help with the diagnosis and treatment of these disorders.

To better understand the variations in gut microbiota in children with different types of epilepsy.

Thirty-seven children with epilepsy were included in the case group, which was further divided into focal (group A, n = 28) and generalized epilepsy groups (group B, n = 9) based on the origin and extent of the seizures. The focal epilepsy group was subdivided into the benign childhood epilepsy with centrotemporal spikes (BECT) (group C, n = 9) and non-BECT groups (group D, n = 19) based on the appearance of typical centrotemporal spikes or spike-wave complexes on the electroencephalogram (EEG). Additionally, 14 healthy children were selected as the control group (group E, n = 14).

Significant differences were observed in the diversity and composition of gut microbiota between the case and control groups. At the genus level, the abundance of Megamonas (P = 0.001), Streptococcus (P<0.001), Romboutsia (P = 0.001), Bacteroides (P<0.05), and Escherichia/Shigella (P<0.05) was significantly higher in the focal epilepsy group than in the control group (0.027 vs. 0.00009, P = 0.001; 0.016 vs. 0.002, P<0.001; 0.013 vs. 0.002, P = 0.001; 0.030 vs. 0.002, P<0.05, respectively). Additionally, Escherichia/Shigella (P<0.05) was more abundant in the case group compared to the control group (0.033 vs. 0.002, P<0.05). Bacteroides (P<0.05) was more abundant in the control group than in the case group. Megamonas (P<0.001) and Collinsella (P<0.05) were significantly more prevalent in the BECT group than in the control group (0.034 vs. 0.00009, P<0.001; 0.014 vs. 0.001, P<0.05, respectively). In the non-BECT group, compared to the control group, Megamonas (P = 0.013), Streptococcus (P<0.001), Romboutsia (P = 0.001), and Escherichia/Shigella (P<0.05) were found in greater abundance (0.023 vs. 0.00009, P = 0.013; 0.018 vs. 0.002, P<0.001; 0.014 vs. 0.002, P = 0.001; 0.037 vs. 0.002, P<0.05, respectively).

Though, there were no statistically significant differences in gut microbiota between the different types of epilepsy, the gut microbiota of children with epilepsy significantly differed from that of healthy controls. The increased abundance of Escherichia/Shigella may lead to the worsening of clinical phenotypes and poor prognosis, and it could be a candidate biomarker to identify the focal epilepsy or even non-benign childhood epilepsy with centrotemporal spikes, potentially providing new therapeutic targets for the future.

BackgroundSleep disturbances often precede motor symptoms in neurodegenerative diseases like Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Neuroinflammation is implicated in PD pathophysiology and may contribute to non-motor symptoms such as sleep disturbances. The Thy1-αSyn mouse model, overexpressing human alpha-synuclein (αSyn), mimics key aspects of PD and DLB, making it valuable for studying related sleep disturbances and neuroinflammatory changes.ObjectiveTo investigate early-stage alterations in sleep architecture, electroencephalographic (EEG) patterns, and neuroinflammation in Thy1-αSyn mice.MethodsWe used telemetric EEG/electromyography (EMG) with video surveillance to compare sleep patterns and EEG spectral power between 2.5- and 4.5-month-old male Thy1-αSyn transgenic mice and wild-type littermates. Neuroinflammation was assessed by examining microglial (Iba1) and astrocytic (GFAP) activation in key sleep-regulating brain regions.ResultsThy1-αSyn mice showed decreased resting wake time and increased non-REM sleep, with altered sleep bout frequency and length, indicating significant sleep architecture changes. Spectral analysis revealed a shift from higher to lower frequency bands, suggesting early neural circuitry disruptions due to αSyn overexpression. Significant microglial activation was observed at 3 months, with astrogliosis progressing by 5 months in key sleep-regulating regions, indicating that neuroinflammation may contribute to the observed sleep disturbances.ConclusionsEarly-stage Thy1-αSyn mice exhibit significant sleep architecture changes, EEG spectral shifts, and neuroinflammatory alterations. These findings suggest that neuroinflammation may play a role in the initial pathophysiological changes in PD and related synucleinopathies. Sleep, EEG, and neuroinflammatory changes could serve as early biomarkers for these diseases.

Although there are numerous options for epilepsy treatment, its effective control continues unsatisfactory. Thus, search for alternative therapeutic options to improve the efficacy/safety binomial of drugs becomes very attractive to investigate. In this context, intranasal administration of antiseizure drugs formulated on state-of-the-art nanosystems can be a promising strategy.

This work gives a comprehensive overview of different intranasal nanosystems for antiseizure drug administration developed and evaluated on preclinical studies over the last 10 years and published in 'PubMed' and 'Web of Science' databases. Additionally, it highlights their pharmaceutical critical quality attributes and in vivo pharmacological outputs that might infer possible results when transposing to clinical trials.

Research into optimized nanosystems encapsulating antiseizure drugs to enhance direct nose-to-brain delivery has increased over the last years. Particularly, the interest in formulating first- and second-generation antiseizure drugs in nanoparticles is here highlighted, having demonstrated its in vivo safety and improvement on pharmacokinetic and efficacy outputs. Still, none of them were brought to clinical trials. Thus, considering the existing barriers between preclinical and clinical trials, if supported by robust and targeted quality by design approaches, intranasal drug delivery can be presented as a valid and superior alternative for epilepsy treatment.

The results of many epidemiological studies suggest a bidirectional causality may exist between epilepsy and Parkinson's disease (PD). However, the underlying molecular landscape linking these two diseases remains largely unknown. This study aimed to explore this possible bidirectional causality by identifying differentially expressed genes (DEGs) in each disease as well as their intersection based on two respective disease-related datasets. We performed enrichment analyses and explored immune cell infiltration based on an intersection of the DEGs. Identifying a protein-protein interaction (PPI) network between epilepsy and PD, and this network was visualised using Cytoscape software to screen key modules and hub genes. Finally, exploring the diagnostic values of the identified hub genes. NetworkAnalyst 3.0 and Cytoscape software were also used to construct and visualise the transcription factor-micro-RNA regulatory and co-regulatory networks, the gene-microRNA interaction network, as well as gene-disease association. Based on the enrichment results, the intersection of the DEGs mainly revealed enrichment in immunity-, phosphorylation-, metabolism-, and inflammation-related pathways. The boxplots revealed similar trends in infiltration of many immune cells in epilepsy and Parkinson's disease, with greater infiltration in patients than in controls. A complex PPI network comprising 186 nodes and 512 edges were constructed. According to node connection degree, top 15 hub genes were considered the kernel targets of epilepsy and PD. The area under curve values of hub gene expression profiles confirmed their excellent diagnostic values. This study is the first to analyse the molecular landscape underlying the epidemiological link between epilepsy and Parkinson's disease. The two diseases are closely linked through immunity-, inflammation-, and metabolism-related pathways. This information was of great help in understanding the pathogenesis, diagnosis, and treatment of the diseases. The present results may provide guidance for further in-depth analysis about molecular mechanisms of epilepsy and PD and novel potential targets.

Epilepsy is a neurological disorder that is major cause of disability in the world. This is most severe medical condition related with different ion channel genes, inflammatory molecules depression and stress. For this purpose, precise diagnostic techniques are available. Genetic polymorphisms are major factors behind the occurrence of many disorders therefore they can be valid for diagnostic purpose. This study emphasis the finding of such markers in Lahore population. Epilepsy-causing gene GABRG2 was selected, and the gene was then examined to detect the presence of polymorphic markers with the help of molecular (PCR) and computational analysis. 50 blood samples of epilepsy patients were collected from Children hospital Lahore, out of which 2 samples were shown positive response for GABRG2 gene, indicating that this gene is becoming the cause of seizures in epilepsy patients. These samples underwent mutational screening, which revealed 6 new mutations in exon 3 region of these samples as a result of disease occurrence. There are no proper treatments of epilepsy offered despite the development of anti-leptic and anti-seizure drugs. To solve this issue, researchers are working to create innovative methods of treating epilepsy, that incorporate the use of herbal remedies. 31 plant compounds have been used in this study but only one compound cyanidin was selected on the base of best binding affinity. Moreover, SwissAdme, QSAR analysis and molecular simulations demonstrated that cyanidin is a best natural drug model which have best responses as compared to other epileptic drugs and can be tested for future application in laboratories.

The high rate of postencephalitic epilepsy (PE) contributes to the unfavorable clinical outcome of herpes simplex virus-1 encephalitis (HSE). We aimed to identify the risk factors and explore possible mechanisms of PE in childhood following HSE. We conducted a retrospective review of children diagnosed with HSE and patients were categorized into two groups based on the presence or absence of PE. Multivariate logistic regression analysis was used to analyze factors associated with PE. Furthermore, cytokine and albumin levels in paired cerebrospinal fluid (CSF) and blood samples during acute HSE were also retrospectively reviewed. 97 HSE patients were included in the study and PE was diagnosed in 46. On multivariate analysis, the features predictive of PE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 9.38, CI 1.71-10.37), focal seizures (7.41, 1.42-16.97), and restricted diffusion on MRI (6.15, 1.16-20.31). The median QAlb value (CSF to serum albumin ratio, a marker of blood-brain-barrier [BBB] integrity), levels of interleukin (IL)-6 and IL-6:IL-10 ratio in CSF were higher in children with PE during acute HSE. However, CSF levels of IL-10 were higher in non-PE patients. Furthermore, greater CSF IL-6 levels were associated with higher QAlb. These results demonstrated that enhanced BBB impairment and exaggerated proinflammatory response may play a role in the pathogenesis of PE following HSE.

Acute subdural hematoma (aSDH) is associated with a high risk of epilepsy, a complication linked to poor outcomes. Craniotomy is a known risk factor, with an epilepsy incidence of approximately 25%. This study evaluated radiomic features from preoperative CT scans to predict epilepsy risk in aSDH patients undergoing craniotomy.

A retrospective analysis of 178 adult aSDH patients treated between 2016 and 2022 identified 64 patients meeting inclusion criteria. Radiomic features (e.g., Feret diameter, elongation, flatness, surface area, and volume) from preoperative CT scans within 24 h of surgery were analyzed alongside clinical factors, including cardiac comorbidities, pupillary response, SOFA score, age, and anticoagulation status.

Of the 64 patients, 18 (28%) developed generalized seizures. Univariate analysis showed significant associations with Feret diameter (p = 0.045), elongation (p = 0.005), cardiac comorbidities (p = 0.017), and SOFA score (p = 0.036). ROC analysis showed excellent discriminatory ability for elongation (AUC = 0.82). Multivariate analysis identified elongation as an independent predictor (p = 0.003); elongation ≥ 1.45 increased seizure risk 7.78-fold (OR = 7.778; 95% CI = 1.969-30.723).

Radiomic features, particularly elongation, may help predict epilepsy risk in aSDH patients undergoing craniotomy. Prospective validation is needed.

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing the entry of harmful pathogens from the bloodstream. However, this barrier also presents a significant obstacle when it comes to delivering drugs for the treatment of neurodegenerative diseases and brain cancer. Recent breakthroughs in nanotechnology have paved the way for the creation of a wide range of nanoparticles (NPs) that can serve as carriers for diagnosis and therapy. Regarding their promising properties, organic NPs have the potential to be used as effective carriers for drug delivery across the BBB based on recent advancements. These remarkable NPs have the ability to penetrate the BBB using various mechanisms. This review offers a comprehensive examination of the intricate structure and distinct properties of the BBB, emphasizing its crucial function in preserving brain balance and regulating the transport of ions and molecules. The disruption of the BBB in conditions such as stroke, Alzheimer's disease, and Parkinson's disease highlights the importance of developing creative approaches for delivering drugs. Through the encapsulation of therapeutic molecules and the precise targeting of transport processes in the brain vasculature, organic NP formulations present a hopeful strategy to improve drug transport across the BBB. We explore the changes in properties of the BBB in various pathological conditions and investigate the factors that affect the successful delivery of organic NPs into the brain. In addition, we explore the most promising delivery systems associated with NPs that have shown positive results in treating neurodegenerative and ischemic disorders. This review opens up new possibilities for nanotechnology-based therapies in cerebral diseases.

To identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).

We examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.

We included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.

Patients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.

Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent seizures originating in the temporal lobe, often affecting patients' physical, cognitive, and social well-being. Despite the availability of antiseizure medication (ASMs), approximately 30% of TLE patients exhibit drug-resistant seizures, emphasizing the need for alternative therapeutic approaches. Ketogenic diets, known for their anticonvulsant effects, have shown promise in managing drug-resistant epilepsy. However, their demanding high-fat, low-carbohydrate regimens pose significant adherence challenges. Medium-chain triglyceride (MCT) offers a viable alternative by inducing ketosis periodically without the need for continuous dietary restrictions. This study evaluated seizure severity, biochemical markers, and immune-related factors in TLE patients. The intervention group received neuro-Capridin caprylate and caprate (n-CAP), while the control group did not. Significant findings included increased plasma ATP and adenosine levels in the treatment group, along with higher expression of ADORA1 and CD73 and reduced expression of ADK. Corresponding protein changes were observed, with increased CD73 and decreased ADK levels. Caprylate and Caprate also elevated regulatory T cells and reduced proinflammatory cytokines (TNF-α, IL-6, IL-1β). These changes were associated with significant reductions in seizure severity and frequency. Intermittent ketogenesis through the consumption of Caprylate and Caprate effectively reduced seizures and improved immune and metabolic markers in drug-resistant TLE patients. These findings highlight its potential as a complementary therapy, warranting further exploration of its long-term impact and underlying molecular mechanisms.

Postencephalitic epilepsy (PEE) is a severe neurological complication following encephalitis. Early identification of individuals at high risk for PEE is important for timely intervention.

To develop a large self-supervised vision foundation model using a big dataset of multi-contrast head MRI scans, followed by fine-tuning with MRI data and follow-up outcomes from patients with PEE to develop a PEE association model.

Retrospective.

Fifty-seven thousand six hundred twenty-one contrast-enhanced head MRI scans from 34,871 patients for foundation model construction, and head MRI scans from 144 patients with encephalitis (64 PEE, 80 N-PEE) for the PEE association model.

1.5-T, 3-T, T1-weighted imaging, T2-weighted imaging, fluid attenuated inversion recovery, T1-weighted contrast-enhanced imaging.

The foundation model was developed using self-supervised learning and cross-contrast context recovery. Patients with encephalitis were monitored for a median of 3.7 years (range 0.7-7.5 years), with epilepsy diagnosed according to International League Against Epilepsy. Occlusion sensitivity mapping highlighted brain regions involved in PEE classifications. Model performance was compared with DenseNet without pre-trained weights.

Performance was assessed via confusion matrices, accuracy, sensitivity, specificity, precision, F1 score, and area under the receiver operating characteristic curve (AUC). The DeLong test evaluated AUC between the two models (P < 0.05 for statistical significance).

The PEE association model achieved accuracy, sensitivity, specificity, precision, F1 score, and AUC of 79.3% (95% CI: 0.71-0.92), 92.3% (95% CI: 0.80-1.00), 68.8% (95% CI: 0.55-0.87), 70.6% (95% CI: 0.61-0.90), 80.0% (95% CI: 0.71-0.93), and 81.0% (95% CI: 0.68-0.92), respectively. A significant AUC improvement was found compared to DenseNet (Delong test, P = 0.03). The association model focused on brain regions affected by encephalitis.

Using extensive unlabeled data via self-supervised learning addressed the limitations of supervised tasks with limited data. The fine-tuned foundation model outperformed DenseNet, which was trained exclusively on task data.

This research develops a model to assess the occurrence epilepsy after encephalitis, a severe brain inflammation condition. By using over 57,000 brain scans, the study trains a computer program to recognize patterns in brain images. The model analyzes whole-brain scans to identify areas commonly affected by the disease, such as the temporal and frontal lobes. It was tested on data from patients with encephalitis and showed better performance than older methods. The model can assess the risk of secondary epilepsy in patients with encephalitis, allowing doctors to intervene early and improve treatment outcomes for those affected by this condition.

4 TECHNICAL EFFICACY: Stage 1.

Hydrogen gas (H2) is an antioxidant with demonstrated neuroprotective efficacy. In this study, we administered H2 via inhalation to rats to evaluate its effects on seizures induced by kainic acid (KA) injection and the underlying mechanism. The animals were intraperitoneally injected with KA (15 mg/kg) to induce seizures. H2 was inhaled 2 h once a day for 5 days before KA administration. The seizure activity was evaluated using Racine's convulsion scale and electroencephalography (EEG). Neuronal cell loss, glial cell activation, and the levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCL2, and CCL3), reactive oxygen species (ROS) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the hippocampus were assessed. The cerebral blood flow of the rats was also evaluated. The results revealed that KA-treated rats presented increased seizure intensity; increased neuronal loss and astrocyte activation; increased levels of ROS, TNF-α, IL-1β, IL-6, CCL2, and CCL3; and reduced Nrf2 phosphorylation levels. Pretreatment with H2 inhalation significantly attenuated seizure intensity; prevented neuronal loss; decreased microglial and astrocytic activation; decreased ROS, TNF-α, IL-1β, IL-6, CCL2 and CCL3 levels; and increased Nrf2 levels. Inhalation of H2 also prevented the KA-induced decrease in cerebral blood flow. These results suggest that pretreatment with H2 inhalation ameliorates KA-induced seizures and inhibits the inflammatory response and oxidative stress, which protects neurons.

Epilepsy continues to pose significant social and economic challenges on a global scale. Existing therapeutic approaches predominantly revolve around neurocentric mechanisms, and fail to control seizures in approximately one-third of patients. This underscores the pressing need for novel and complementary treatment approaches to address this gap. An increasing body of literature points to a role for glial cells, including microglia and astrocytes, in the pathogenesis of epilepsy. Notably, microglial cells, which serve as pivotal inflammatory mediators within the epileptic brain, have received increasing attention over recent years. These immune cells react to epileptogenic insults, regulate neuronal processes, and play diverse roles during the process of epilepsy development. Additionally, astrocytes, another integral non-neuronal brain cells, have garnered increasing recognition for their dynamic contributions to the pathophysiology of epilepsy. Their complex interactions with neurons and other glial cells involve modulating synaptic activity and neuronal excitability, thereby influencing the aberrant networks formed during epileptogenesis. This review explores the alterations in microglial and astrocytic function and their mechanisms of communication following an epileptogenic insult, examining their contribution to epilepsy development. By comprehensively studying these mechanisms, potential avenues could emerge for refining therapeutic strategies and ameliorating the impact of this complex neurological disease.

Increasing evidence from fluid biopsies suggests activation and injury of glial cells in epilepsy. The prevalence of clinical and subclinical seizures in neurodegenerative conditions such as Alzheimer's disease, frontotemporal dementia, and others merits review and comparison of the effects of seizures on glial markers in epilepsy and neurodegenerative diseases with concomitant seizures. Herein, we revisit preclinical and clinical reports of alterations in glial proteins in cerebrospinal fluid and blood associated with various types of epilepsy. We consider shared and distinct characteristics of changes in different age groups and sexes, in humans and animal models of epilepsy, and compare them with those reported in biofluids in neurodegenerative diseases. Our analysis indicates a significant overlap of glial response in these prevalent neurological conditions.

There is growing evidence that interleukin (IL)-6 plays an important role in neurological and psychiatric disorders. This editorial comments on the study published in the recent issue of the World Journal of Psychiatry, which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence. The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities. IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory processes associated with epilepsy. Furthermore, IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy, highlighting its involvement in neuropsychiatric comorbidities. In summary, IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications. Future research should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes, stages and neuropsychiatric comorbidities of epilepsy, with the aim of developing more precise and effective interventions. Furthermore, the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epilepsy warrants further investigation.

Febrile infection-related epilepsy syndrome (FIRES) is a rare epilepsy syndrome with unclear pathogenesis, characterized by fever-induced, super-refractory status epilepticus and high mortality. Studies have shown that ketogenic diet (KD) is effective in controlling convulsions in FIRES, but its mechanisms are unclear. This paper intends to summarize the mechanisms by which KD may exert effects against FIRES. Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin (IL)-6, IL-8, IL-10, and so on. KD may exert anti-FIRES effects through several potential inflammatory pathways, including nuclear factor -κB (NF-κB) and NLR family pyrin domain containing 3 (NLRP3). Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation. These mechanisms need to be further investigated.

Rheumatoid Arthritis (RA) is a progressive autoimmune condition inflicting serious threats to people's life and health by causing severe pain and joint destruction. It affects not only bones and joints but also causes comorbid conditions and shortens the lifetime. The interactions and synergistic effects of comorbid disease with RA are not yet well studied. Hence, understanding how these conditions will collectively affect the progression and outcome of RA is the current area of research. Identification of RA and comorbidities associated with target genes may uncover diagnosis and treatment methodologies. This review is to provide an overview of the interlinking approach of Rheumatoid Arthritis with its comorbid conditions and its systemic complications using bioinformatic techniques which would be useful to identify the genes and pathways that are in common for both RA and comorbid diseases. It would also emphasize the significance of bioinformatics in comparing the pathological features of RA and comorbid diseases. With the help of bioinformatics, valuable insights into the mechanism underlying Rheumatoid arthritis and comorbid diseases would be better understood.

In the central nervous system, triggering receptor expressed on myeloid cells 2 (TREM2) is exclusively expressed by microglia and is critical for microglial proliferation, migration, and phagocytosis. Microglial TREM2 plays an important role in neurodegenerative diseases, such as Alzheimer's disease and amyotrophic lateral sclerosis. However, little is known about how TREM2 affects microglial function within epileptogenesis. To investigate this, we utilized male TREM2 knockout (KO) mice within the intra-amygdala kainic acid seizure model. Electroencephalographic analysis, immunocytochemistry, and RNA sequencing revealed that TREM2 deficiency significantly promoted seizure-induced pathology. We found that TREM2 KO increased both the severity of acute status epilepticus and the number of spontaneous recurrent seizures characteristic of chronic focal epilepsy. Phagocytic clearance of damaged neurons by microglia was also impaired by TREM2 KO and reduced phagocytic activity correlated with increased spontaneous seizures. Analysis of human tissue from patients who underwent surgical resection for drug resistant temporal lobe epilepsy also showed a negative correlation between expression of the microglial phagocytic marker CD68 and focal to bilateral tonic-clonic generalized seizure history. These results indicate that microglial TREM2 and phagocytic activity are important to epileptogenic pathology.

The aim of this retrospective study was to investigate the importance of leukocyte, neutrophil, lymphocyte, and neutrophil/lymphocyte (NLR) ratios in epileptic seizure recurrence and whether there is a relationship between them.

To evaluate the predictive value of leukocyte, neutrophil, lymphocyte, and monocyte parameters in assessing the likelihood of seizure recurrence in epilepsy patients.

Sixty-five epilepsy patients who were on follow-up for epilepsy were included in the study. The study group consisted of epilepsy patients who had routine complete blood counts taken within the first 24 hours of emergency room visits due to seizures and for control purposes at outpatient clinic visits. The parameters examined were leukocyte, neutrophil, lymphocyte, platelet counts (PLT) (×10³ mm³), mean platelet volume (MPV), and NLR. NLR was calculated by dividing the absolute number of neutrophils by the absolute number of lymphocytes.

Leukocyte, neutrophil, NLR, and monocyte values (P < 0.001) were significantly higher in patients with seizure recurrence in the first 30 days compared to those without recurrence. The predictive value of leukocyte, neutrophil, NLR, and monocyte parameters for seizure recurrence was assessed using receiver operating characteristic (ROC) analysis. Since the area under the curve (AUC) value for NLR was larger than that of neutrophil and monocyte values, the diagnostic performance of NLR was found to be superior. For NLR, the AUC value was 0.73 (95% confidence interval: 0.639-0.807, P = 0.0001), with sensitivity and specificity of 52.31% and 94.23%, respectively. NLR had the highest predictive value for seizure recurrence.

Our study suggests that neutrophil-mediated inflammation plays a role in epileptic seizures and that monocyte values are also important. NLR and monocyte values may serve as predictive biomarkers for seizure recurrence.