Apr 14, 2017

Mutant IDH1 and seizures in patients with glioma

Neurology
Hao ChenCraig Horbinski

Abstract

Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons. Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5. Preoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1wt) patients and in 59%-74% of IDH1mut patients (p < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, p < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-...Continue Reading

  • References38
  • Citations19

Citations

Mentioned in this Paper

Chromosomes, Human, Pair 1
Tumor Cells, Uncertain Whether Benign or Malignant
Microelectrodes
alpha-hydroxyglutarate, disodium salt
Neoplastic Cell
Epilepsy
Neurons
Antagonist Muscle Action
Malignant Neoplasm of Temporal Lobe
Inhibitors

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