Focal corticarl dysplasia in epilepsy is associated with GABA increase

Neuroimage Clin. 2021;31:102763. doi: 10.1016/j.nicl.2021.102763. Epub 2021 Jul 14.

Abstract

Purpose: Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy; however the underlying epileptogenic mechanisms of FCD metabolism in epilepsy patients remain unclear. The aim of this study is to detect alterations of γ-aminobutyric acid (GABA), glutathione (GSH), and the composite of glutamate and glutamine (Glx) in MRI-typical and neuropathologically confirmed FCD-associated epilepsy using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES).

Materials and methods: Fourteen epileptic patients suspected to be caused by FCD and 14 healthy controls were enrolled prospectively in this study; all subjects underwent a 3 T MRI scan, including 3D T1 weighted imaging and HERMES. The GABA signal detected by HERMES also contains signals from macromolecules and homocarnosine, so it is referred as GABA+. Signals of GABA+, GSH and Glx detected by HERMES from tumor foci, contralateral cerebral regions, and healthy controls were quantified using Gannet. Fitting errors and signal to noise ratios (SNRs) of GABA + signals were also recorded. Differences of GABA+, GSH, Glx, fitting error and SNR of GABA + among three groups were analyzed using linear mixed effects models.

Results: Twelve FCD-associated epilepsy patients (7 females, aged 21.9 ± 9.3 years) and 12 matched healthy controls (7 females, aged 22.8 ± 9.8 years) were finally enrolled in this study. ANOVA results indicated that GABA levels were significantly increased in FCD foci compared with contralateral regions (p = 0.008) and with healthy controls (p = 0.003), while no difference was found in GSH and Glx levels. No difference of fitting errors or SNR of GABA + was found among FCD foci, contralateral regions and healthy controls.

Conclusions: Increased GABA levels were found in FCD foci that indicated GABA may play a central role in the pathophysiology of FCD patients with epilepsy.

Keywords: Epilepsy; Focal cortical dysplasia; Glutamate; Glutathione; γ-Aminobutyric acid (GABA).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epilepsy* / diagnostic imaging
  • Female
  • Glutathione
  • Humans
  • Magnetic Resonance Imaging
  • Malformations of Cortical Development* / complications
  • Malformations of Cortical Development* / diagnostic imaging
  • gamma-Aminobutyric Acid

Substances

  • gamma-Aminobutyric Acid
  • Glutathione