Idiopathic focal epilepsy in children and adolescents: roles of perinatal pain, amyloid-β oligomers and DHA (omega-3 fatty acid) deficiency

In children and adolescents, epilepsy is a chronic disease characterized by the paroxysmal onset of seizures resulting from abnormal cellular excitability. Idiopathic epilepsy is a disease of apparent spontaneous origin whose cause or mechanism is unknown. This opinion review describes the pathogenetic mechanisms behind epilepsy, as well as its generating and aggravating factors. A triggering factor is perinatal pain that generates amyloid-β (Aβ) oligomers that is not completely eliminated. An aggravating factor is a deficiency of DHA — due to diet or specific FADS2 alleles (Δ6-desaturase gene) — which is a preferential ligand of the PPARα-RXRα and PPARɣ-RXRα heterodimers. These two factors have impacts on the glutamatergic pathways: (i) metabolic homeostasis as a function of stimulation (regional blood flow); (ii) flow rate of GLUT-1 transporters (glucose, ascorbic acid precursor); (iii) regulation of oxidative stress; (iv) repair of oxidative injuries; (v) priority given to the non-amyloidogenic pathway; (vi) proteolysis of Aβ residues and their removal. The originality of this approach resides in particular in highlighting the fundamental role played by DHA. Understanding the risk factors can help prevent epilepsy onset, decrease epilepsy prevalence in children and adolescents and aid healthcare professionals in identifying high-risk populations and making plausible preventive nutritional measures based on DHA supplementation very early.