Interactions between in vivo neuronal-glial markers, side of hippocampal sclerosis, and pharmacoresponse in temporal lobe epilepsy

Epilepsia. 2020 May;61(5):1008-1018. doi: 10.1111/epi.16509. Epub 2020 Apr 29.

Abstract

Objective: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE).

Methods: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility.

Results: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance.

Significance: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.

Keywords: MRI; antiepileptic drugs; magnetic resonance spectroscopy; metabolomics; partial seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use*
  • Biomarkers
  • Case-Control Studies
  • Creatine / metabolism
  • Drug Resistant Epilepsy / drug therapy
  • Drug Resistant Epilepsy / pathology*
  • Epilepsy, Temporal Lobe / diagnostic imaging
  • Epilepsy, Temporal Lobe / drug therapy*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / pathology
  • Female
  • Glutamic Acid / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology*
  • Humans
  • Inositol / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • N-Methylaspartate / metabolism
  • Neuroglia / pathology*
  • Neuroimaging
  • Neurons / pathology*
  • Proton Magnetic Resonance Spectroscopy
  • Sclerosis
  • Treatment Outcome
  • Young Adult

Substances

  • Anticonvulsants
  • Biomarkers
  • Glutamic Acid
  • Inositol
  • N-Methylaspartate
  • Creatine