Drug-resistant epilepsy (DRE) presents significant challenges in treatment and management. While seizure-related alterations in peripheral immune players are increasingly recognized, the involvement of the immune complement system remains insufficiently explored in DRE. We studied complement components and their relationship to cytokine profiles in serum samples from 46 DRE patients and 45 matched healthy controls. We examined relationships between these molecules and clinical outcomes, including epilepsy duration, intelligence scores, and age. We identified DRE-associated complement decreases, including reduced levels of C1q, Factor H, C4, C4b, C3, and C3b/iC3b, as well as elevated bFGF. DRE females showed dysregulation of the classical complement pathway and lower TNFα and interleukin-8 compared to healthy females. DRE males exhibited dysregulation of the classical, lectin, and terminal complement pathways, with trends of increased CCL2 and CCL5 compared to healthy males. Specific complement and inflammatory markers (C2, IL-8, and IL-9) correlated with full-scale IQ scores in DRE patients. Our study reveals significantly lower levels of circulating complement components in DRE and sex-specific complement dysregulation and cytokine imbalances. These findings suggest an underlying peripheral immune system vulnerability that may be sex-dependent and warrants further investigation in DRE.

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.

Drug-resistant epilepsy (DRE) poses significant challenges in treatment and management. While seizure-related alterations in peripheral immune players are increasingly recognized, the involvement of the complement system, central to immune function, remains insufficiently explored in DRE. This study aimed to investigate the levels of complement system components and their association with cytokine profiles in patients with DRE.

We analyzed serum samples from DRE patients (n = 46) and age- and sex-matched healthy controls (n = 45). Complement components and cytokines were quantified using Multi- and Single-plex ELISA. Statistical analyses examined relationships between complement molecules, cytokines, and clinical outcomes including epilepsy duration, Full-Scale Intelligence Quotient (FSIQ) scores, and age.

We found common alterations in all DRE cases, including significant complement deficiencies (C1q, Factor H, C4, C4b, C3, and C3b/iC3b) and detectable bFGF levels. DRE females showed significantly lower levels of TNFα and IL-8 compared to healthy females. We observed a trend towards elevated CCL2 and CCL5 levels in DRE males compared to healthy males. These findings suggest potential sex dimorphism in immune profiles. Our analysis also indicated associations between specific complement and inflammatory markers (C2, IL-8, and IL-9) and Full-Scale Intelligence Quotient (FSIQ) scores in DRE patients.

Our study reveals sex-specific peripheral complement deficiencies and cytokine dysregulation in DRE patients, indicating an underlying immune system vulnerability. These findings provide new insights into DRE mechanisms, potentially guiding future research on complement and cytokine signaling toward personalized treatments for DRE patients.

Background/Objectives: Determining the outcome of epilepsy is crucial for making proactive and timely treatment decisions and for counseling patients. Recent research efforts have focused on using various imaging techniques and EEG for prognostication; however, there is insufficient evidence regarding the role of blood parameters. Our study aimed to investigate the additional prognostic value of routine blood parameters in predicting epilepsy outcomes. Methods: We analyzed data from 1782 patients who underwent routine blood tests within 90 days of their first visit and had a minimum follow-up duration of three years. The etiological types were structural (35.1%), genetic (14.2%), immune (4.7%), infectious (2.9%), and unknown (42.6%). The outcome was defined as the presence of seizures in the last year. Results: Initially, a multivariate analysis was conducted based on clinical variables, MRI data, and EEG data. This analysis revealed that sex, age of onset, referred cases, epileptiform discharge, structural etiology, and the number of antiseizure medications were related to the outcome, with an area under the curve (AUC) of 0.705. Among the blood parameters, fibrinogen, bilirubin, uric acid, and aPTT were significant, with AUCs of 0.602, 0.597, 0.455, and 0.549, respectively. Including these blood parameters in the analysis slightly improved the AUC to 0.710. Conclusions: Some blood parameters were found to be related to the final outcome, potentially paving the way to understanding the mechanisms of epileptogenesis and drug resistance.

Epilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations.

We conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas.

A total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY & BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including "recognitive impairment" and "mental health," indicating potential future research hotspots and trends.

This study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.

Epilepsy is a chronic neurological disorder with recurrent unprovoked seizures, affecting ~ 65 million worldwide. Evidence in patients with epilepsy and animal models suggests a contribution of neuroinflammation to epileptogenesis and the development of epilepsy. Interleukins (ILs), as one of the major contributors to neuroinflammation, are intensively studied for their association and modulatory effects on ictogenesis and epileptogenesis. ILs are commonly divided into pro- and anti-inflammatory cytokines and therefore are expected to be pathogenic or neuroprotective in epilepsy. However, both protective and destructive effects have been reported for many ILs. This may be due to the complex nature of ILs, and also possibly due to the different disease courses that those ILs are involved in. In this review, we summarize the contributions of different ILs in those processes and provide a current overview of recent research advances, as well as preclinical and clinical studies targeting ILs in the treatment of epilepsy.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

Electroconvulsive therapy (ECT) is a widely used therapeutic option of drug-refractory psychiatric disorders. ECT treats psychiatric symptoms by inducing brief controlled seizures through electrical stimulation, but ECT does not generally cause prolonged seizures or epilepsy. However, several studies have reported cases of prolonged seizures after ECT. This review aimed to determine the mechanism of epileptogenesis with neurobiological changes after ECT. Contrary to epileptogenesis by ECT, several cases have reported that ECT was successfully applied for treatment of refractory status epilepticus. In addition, ECT might be applied to hyperkinetic movement and psychiatric symptoms of encephalitis. We also investigated the anticonvulsant mechanism of ECT and how it controls encephalitis symptoms.

Type 2 diabetes mellitus (T2DM) is a global health burden that leads to an increased morbidity and mortality rate arising from microvascular and macrovascular complications. Epilepsy leads to complications that cause psychological and physical distress to patients and carers. Although these conditions are characterized by inflammation, there seems to be a lack of studies that have evaluated inflammatory markers in the presence of both conditions (T2DM and epilepsy), especially in low-middle-income countries where T2DM is epidemic. Summary findings: In this review, we describe the role of immunity in the seizure generation of T2DM. Current evidence shows an increase in the levels of biomarkers such as interleukin (IL-1β, IL-6, and IL-8), tumour necrosis factor-α (TNF-α), high mobility group box-1 (HMGB1), and toll-like receptors (TLRs) in epileptic seizures and T2DM. However, there is limited evidence to show a correlation between inflammatory markers in the central and peripheral levels of epilepsy.

Understanding the pathophysiological mechanism behind epileptic seizures in T2DM through an investigation of immunological imbalances might improve diagnosis and further counter the risks of developing complications. This might also assist in delivering safe and effective therapies to T2DM patients affected, thus reducing morbidity and mortality by preventing or reducing associated complications. Moreover, this review also provides an overview approach on inflammatory cytokines that can be targeted when developing alternative therapies, in case these conditions coexist.

As 30% of epileptic patients remain drug-resistant, seizure prediction is vital. Induction of epileptic seizure is a complex process that can depend on factors such as intrinsic neuronal excitability, changes in extracellular ion concentration, glial cell activity, presence of inflammation and activation of the blood−brain barrier (BBB). In this study, we aimed to assess if levels of serum proteins associated with BBB can predict seizures. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 49 patients with epilepsy who were seizure-free for a minimum of seven days and measured by ELISA. The examination was repeated after 12 months. An extensive medical history was taken, and patients were subjected to a follow-up, including a detailed history of seizures. Serum levels of MMP-2, MMP-9, TIMP-1, CCL-2, and P-selectin differed between the two time points (p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p = 0.0035, respectively). General linear model analyses determined the predictors of seizures. Levels of MMP-2, MMP-9, and CCL-2 were found to influence seizure count in 1, 3, 6, and 12 months of observation. Serum levels of MMP-2, MMP-9, and CCL-2 may be considered potential biomarkers for seizure prediction and may indicate BBB activation.