Metabolomics Provides Novel Insights into Epilepsy Diagnosis and Treatment: A Review

Epilepsy is one of the most common diseases of the central nervous system. The diagnosis of epilepsy mainly depends on electroencephalograms and symptomatology, while diagnostic biofluid markers are still lacking. In addition, approximately 30% of patients with epilepsy (PWE) show a poor response to the currently available anti-seizure medicines. An increasing number of studies have reported alterations in the blood, brain tissue, cerebrospinal fluid and urine metabolome in PWE and animal models of epilepsy. The aim of this review was to identify potential metabolic biomarkers and pathways that might facilitate diagnostic, therapeutic and prognostic determination in PWE and the understanding of the pathogenesis of the disease. The PubMed and Embase databases were searched for metabolomic studies of PWE and epileptic models published before December 2020. The study objectives, types of models and reported differentially altered metabolites were examined and compared. Pathway analyses were performed using MetaboAnalyst 5.0 online software. Thirty-five studies were included in this review. Metabolites such as glutamate, lactate and citrate were disturbed in both PWE and epileptic models, which might be potential biomarkers of epilepsy. Metabolic pathways including alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism; glycerophospholipid metabolism; glyoxylate and dicarboxylate metabolism; and arginine and proline metabolism were involved in epilepsy. These pathways might play important roles in the pathogenesis of the disease. This review summarizes metabolites and metabolic pathways related to epilepsy and provides a novel perspective for the identification of potential biomarkers and therapeutic targets for epilepsy.