Molecular Mechanism Involved in the Pathogenesis of Early-Onset Epileptic Encephalopathy

Abstract

Recent studies have shown that neurologic inflammation may both precipitate and sustain seizures, suggesting that inflammation may be involved not only in epileptogenesis but also in determining the drug-resistant profile. Extensive literature data during these last years have identified a number of inflammatory markers involved in these processes of “neuroimmunoinflammation” in epilepsy, with key roles for pro-inflammatory cytokines such as: IL-6, IL-17 and IL-17 Receptor (IL-17R) axis, Tumor-Necrosis-Factor Alpha (TNF-α) and Transforming-Growth-Factor Beta (TGF-β), all responsible for the induction of processes of blood-brain barrier (BBB) disruption and inflammation of the Central Nervous System (CNS) itself. Nevertheless, many of these inflammatory biomarkers have also been implicated in the pathophysiologic process of other neurological diseases. Future studies will be needed to identify the disease-specific biomarkers in order to distinguish epilepsies from other neurological diseases, as well as recognize different epileptic semiology. In this context, biological markers of BBB disruption, as well as those reflecting its integrity, can be useful tools to determine the pathological process of a variety of neurological diseases. However; how these molecules may help in the diagnosis and prognostication of epileptic disorders remains yet to be determined. Herein, authors present an extensive literature review on the involvement of both, systemic and neuronal immune systems, in the early onset of epileptic encephalopathy.

Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability: A Prospective Study and Updated Meta-Analysis

“…In our study, we proposed two explanations for genetic factors increasing DRE risk during infancy with epilepsy and NDD: First, during the neonatal or infancy period, early infantile epileptic encephalopathy accounts for a major part of genetic epilepsy, which are di cult to treat and often medically refractory [52]. Second, on the basis of several hypotheses proposed on DRE, including hypotheses regarding pharmacokinetics, intrinsic severity, neural networks, gene variants, transporters, and targets [53], we assumed that a sustained "neuroimmunoin ammatory" status can be implicated as not only epileptogenic but also indicative of a drug-resistant pro le [54]. Additional relevant cell line-and animal model-based studies are thus warranted.…”

Genetic factors and the risk of drug-resistant epilepsy in young children with epilepsy and neurodevelopment disability

“…[ 52 ] Second, on the basis of several hypotheses proposed on DRE, including hypotheses regarding pharmacokinetics, intrinsic severity, neural networks, gene variants, transporters, and targets, [ 53 ] we assumed that a sustained “neuroimmunoinflammatory” status can be implicated as not only epileptogenic but also indicative of a drug-resistant profile. [ 54 ] Additional relevant cell line– and animal model–based studies are thus warranted.…”

Fatal Suicidal Attempt by Deliberate Ingestion of Nicotine-containing Solution in Childhood-onset Depression Mediated through Internet Suicide Guideline: A Case Report

“…This is slightly different from the pathogenesis of reversible epileptic or hepatic encephalopathy, as cytokine storm of interleukins are responsible in epileptic process, while increased ammonia causing osmotic imbalance and ultimately brain edema in hepatic reversible or irreversible encephalopathy depending on severity of damage. 14 , 15 …”