Role Of Inflammation In Epilepsy Research Articles

Exploring the association of disease-modifying therapies for multiple sclerosis and BTK inhibitors with epilepsy.

Multiple lines of evidence suggest a role of inflammation in epilepsy. Seizure incidence in patients with multiple sclerosis (MS) is twofold to threefold higher than the age-matched general population. To explore the association of MS disease-modifying therapies (DMTs) and FDA-approved Bruton tyrosine kinase inhibitors (for lymphocytic malignancies) with the occurrence of epilepsy using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Secondary analysis of the FAERS database. We conducted a disproportionality analysis of FAERS between 2003-Q4 and 2023-Q3. MS DMTs and the Bruton tyrosine kinase inhibitor, ibrutinib, were included in the analysis. An inverse association was defined by a 95% confidence interval (CI) upper limit of reporting odds ratio (ROR) <1. We found an inverse association of ibrutinib, ocrelizumab, ofatumumab, rituximab, and teriflunomide with epilepsy. The strongest inverse association was seen with ibrutinib (ROR: 0.338; 95% CI: 0.218-0.524). Our findings suggest the possibility of considering these medications for repurposing opportunities in epilepsy and support a potential pathogenic role of leukocyte subsets in seizure perpetuation.

CSF neopterin, quinolinic acid and kynurenine/tryptophan ratio are biomarkers of active neuroinflammation

Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy. Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n=90) and epilepsy group (n=80), who were compared with three control groups including neurogenetic and structural (n=76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n=63), and headache (n=32). There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p<0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p=0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p≤0.0003), which was evident in most epilepsy subgroups. Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases. Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.

The role of inflammation in epilepsy

Epilepsi, dünya çapında ve ülkemizde oldukça yaygın görülen hastalıklardan biridir. İnflamatuvar mediatörler ve immün hücrelerin üretilmesi ile epileptik nöbetlerin tekrarı arasındaki ilişki hakkında gün geçtikçe deneysel ve klinik çalışmaların ışığında birbirini destekleyen veriler ortaya çıkmaktadır. Bundan dolayı epilepsi ve inflamasyon ilişkisi ilgi çekmektedir. Bu derlemede epilepsi ile inflamasyon ilişkisi incelenmiştir.

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery.

Increasing amounts of evidence support the role of inflammation in epilepsy. This study was done to evaluate serum follow-up of IL-1β and IL-6 levels, as well as their concentration in the neocortex, and the relationship of central inflammation with NF-κB and annexin V in drug-resistant temporal lobe epileptic (DRTLE) patients submitted to surgical treatment. Peripheral and central levels of IL-1β and IL-6were measured by ELISA in 10 DRTLE patients. The sera from patients were taken before surgery, and 12 and 24 months after surgical treatment. The neocortical expression of NF-κB was evaluated by western blotting and annexin V co-localization with synaptophysin by immunohistochemistry. The neocortical tissues from five patients who died by non-neurological causes were used as control. Decreased serum levels of IL-1 and IL-6 were observed after surgery; at this time, 70% of patients were seizure-free. No values of IL-1 and IL-6 were detected in neocortical control tissue, whereas cytokine levels were evidenced in DRTLE. Increased NF-κB neocortex expression was found and the positive annexin V neurons were more obvious in the DRTLE tissue, correlating with IL-6 levels. The follow-up study confirmed that the inflammatory alterations disappeared one year after surgery, when the majority of patients were seizure-free, and the apoptotic death process correlated with inflammation.

C-reactief proteïneconcentraties in het serum van honden met idiopathische epilepsie

Inflammatoire reacties bij honden zijn geassocieerd met systemische veranderingen in het serum, de acute fase respons genaamd. Deze gaat gepaard met veranderde concentraties acutefase-eiwitten in het serum. Het C-reactief proteïne (CRP) is een positief acutefase-eiwit en stijgt bijgevolg bij een ontsteking. Er bestaat veel onduidelijkheid over de relatie tussen epilepsie en ontsteking. Daarom werd in deze studie de rol van ontsteking onderzocht bij honden met idiopathische epilepsie (IE). Drie doelstellingen werden vooropgesteld: 1. het meten van serum-CRP-concentraties bij honden met IE en bij gezonde honden, 2. het meten van serum-CRP-concentraties bij honden met acute clusteraanvallen en bij honden met geïsoleerde aanvallen en 3. het opvolgen van de evolutie in serum-CRP-concentraties in de tijd na de laatste epilepsieaanval. In deze studie kon geen significant verschil in serum-CRPconcentratie tussen honden met IE en de honden van de controlegroep worden aangetoond. Verder waren de gemiddelde serum-CRP-concentraties hoger bij honden met clusteraanvallen (8,3 mg/l) dan bij honden met geïsoleerde aanvallen (7,8 mg/l). Deze resultaten waren echter statistisch niet significant (P = 0,077). Ten slotte werd een statistisch niet-significante daling in serum-CRP-concentraties gezien na de laatste epileptische aanval bij de honden met IE (P = 0,077).

Inflammation and epilepsy in the developing brain: clinical and experimental evidence.

There is an increasing evidence to support a role of inflammatory processes in epilepsy. However, most clinical and experimental studies have been conducted in adult patients or using adult rodents. The pediatric epilepsies constitute a varied group of diseases that are most frequently age specific. In this review, we will focus on the possible role of inflammation in pediatric epilepsy syndromes. We will first describe the clinical data available and provide an overview of our current understanding of the role of inflammation in these clinical situations. We will then review experimental data regarding the role of inflammation in epilepsy in the developing brain. To summarize, inflammation contributes to seizure precipitation, and reciprocally, prolonged seizures induce inflammation. There is also a relationship between inflammation and cell injury following status epilepticus, which differs according to the developmental stage. Finally, inflammation seems to contribute to epileptogenesis even in the developing brain. Based on the available data, we highlight the need for further studies dissecting the exact role of inflammation in epilepsy during development.

Causes of CNS Inflammation and Potential Targets for Anticonvulsants

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

The role of inflammation in epilepsy

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.

The Role of Inflammation in Epilepsy

The Role of Inflammation in Epilepsy

Inflammation and epilepsy.

In recent years, increasing evidence has indicated that immune and inflammatory reactions occur in brain in various central nervous system (CNS) diseases. Furthermore, inflammatory processes, such as the production of proinflammatory cytokines and related molecules, have been described in brain after seizures induced in experimental models and in clinical cases of epilepsy. Although little is known about the role of inflammation in epilepsy, it has been hypothesized that activation of the innate immune system and associated inflammatory reactions in brain may mediate some of the molecular and structural changes occurring during and after seizure activity. Whether the innate immune response that takes place in epileptic tissue is beneficial or noxious to the CNS is still an open and intriguing question that should be addressed by further investigations.