Glycosylation disorders in pediatric epilepsy: pathophysiology, imaging and precision therapy

Epilepsy is a common neurological disorder in children and about 30% of children with epilepsy develop drug-resistant epilepsy. Epilepsy resulting from genetic variations and structural brain abnormalities has been extensively studied. Based on the current evidence, however, glycosylation, a major post-translational modification on over 70% of human brain proteins, is necessary for the stability of neural networks. This article delves into the many aspects of glycosylation abnormalities in epilepsy, including impairing early neural development, affecting the transport and function of ion channels, disrupting synaptic receptor and vesicular transport, and exacerbating neuroinflammatory damage. At the same time, the relationship between glycosylation and epilepsy is bidirectional. Glycosylation disorders induce seizures and chronic seizures induce a glycomic remodeling of the brain. This forms a vicious cycle and becomes a "background mechanism" of susceptibility and drug resistance for epilepsy. Specific and individualized approaches to clinical management must be adopted, including substrate supplementation, the ketogenic diet, and new specific drugs, such as enzyme inhibitors, pharmacological chaperones, and gene therapy. Future studies should focus on combining multi-omics data with high resolution neuroimaging to gain insights into the spatiotemporal dynamics of glycosylation abnormalities; the development of more targeted drugs according to the level of post-translational modification; and the formulation of more precise intervention strategies involving pediatric patients.