Association of preoperative seizures with tumor metabolites quantified by magnetic resonance spectroscopy in gliomas

Abstract

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-l-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.

Metabolomics in High Grade Gliomas

“…Studies indicate that gliomas release glutamate and this has been implicated in tumor expansion (Takano et al, 2001), cellular edema (Savaskan et al, 2008), and tumor associated excitotoxicity and epilepsy (Buckingham and Robel, 2013;de Groot and Sontheimer, 2011;Yuen et al, 2012). Interestingly, Nakae et al found that while higher glutamate concentration was in IDH-wt glioma relative to IDH-mt, glutamate was not associated with high preoperative seizure frequency (Nakae et al, 2021). Rather, levels of total N-acetyl-L-aspartate were found to be statistically correlated and were independent predicators of preoperative seizures (Nakae et al, 2021).…”

“…Interestingly, Nakae et al found that while higher glutamate concentration was in IDH-wt glioma relative to IDH-mt, glutamate was not associated with high preoperative seizure frequency (Nakae et al, 2021). Rather, levels of total N-acetyl-L-aspartate were found to be statistically correlated and were independent predicators of preoperative seizures (Nakae et al, 2021). Glutamate can be derived from glutamine, the most abundant amino acid in the body.…”

Applied Fence-Post Techniques Using Deep Electrodes Instead of Catheters for Resection of Glioma Complicated with Frequent Epileptic Seizures: A Case Report

“…Seizures are frequently complicated by low-grade gliomas, such as adult diffuse gliomas harboring mutant isocitrate dehydrogenase ( IDH ), some pediatric low-grade gliomas, or some glioneuronal and neuronal tumors [ 1 , 2 , 3 , 4 ]. Adult diffuse glioma patients with IDH mutations are younger than patients with adult diffuse gliomas without mutant IDH [ 5 , 6 ].…”