Prostaglandin E2 as neuroinflammatory target in childhood resistant epilepsies
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Aim: Childhood epilepsies are a diverse group of neurological disorders with a multifaceted clinical course caused by a range of aetiological factors. Despite new Anti Seizure Drugs (ASDs), drug resistance remains a significant hurdle in treatment. Growing evidence links epilepsy to inflammatory processes, especially in drug-resistant cases. A number of neuroinflammatory pathways involving cytokines have been identified in the pathogenesis of drug resistant epilepsy, including the axis of Cox2–PGE2-Prostaglandin E2 receptor 1 that has been shown to affect blood-brain barrier function, and drug pharmacokinetics through upregulation of multidrug effluxers. We measured the plasma PGE2 levels aiming to determine PGE2 importance in epilepsy-associated inflammation and antiepileptic drug (AED) response for the patients with different types of epilepsy .
Methods: a prospective review of clinical and paraclinical data of study group (Group 1), including patients with epilepsy who had ongoing long term follow-up in two subgroups: Group 1A-Patients diagnosed with epilepsy -seizure-free on AED therapy, Group 1B- patients with refractory epilepsy and healthy control group (Group2). Serum samples tested for PGE2 levels(interquartile ranges/pg/ml) by the enzyme-linked immunosorbent assay (ELISA).
Results: Measured serum PGE2 the median interquartile ranges (IQR) were higher and in broader ranges for epilepsy patients all together 512 pg/ml (324.5-970.0 )compared to healthy controls 406 pg/ml (278.7-541.4) , but not significantly different across the epilepsy study groups (p>0.05). Only Valproate responders showed reduced PGE2 mean IQR 490 pg/ml.
Conclusions: Our findings align with preclinical models, suggesting a potential target on molecular basis for overcoming drug resistance, which is a major challenge and key toward precision medicine in epilepsy management.
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