Increased Frequency of Presenting with Seizures in Patients with Isocitrate Dehydrogenase 1 (IDH1) Mutant Gliomas

Arthur Po-Fei Chou, MD, PhD1, Harry Ching1, Stephen Chang1, Jose Carrillo, MD1, Shadi Lalezari1, Marko Spasic1, Winward Choy1, Andrew Kim1, Julia Selfridge1, Jennifer Quan1, Yiannis Philippou1, Justin Dye1, Horacio Soto1, Daniel Nagasawa1, Gary Mathern1, Richard Green1, Issac Yang1, Robert Prins1, Albert Lai1

1Los Angeles, CA United States

Keywords: glioma, gene, seizures, molecular biology, epilepsy

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     Low-grade and secondary glioblastoma often have mutations in isocitrate dehydrogenase 1 (IDH1). IDH1 mutation leads to the production of 2-hydroxyglutarate (2-HG), which may activate NMDA receptors.
     The aim of this study is to examine if IDH1 mutation is associated with increased frequency of seizures in glioma patients.
     Our cohort included 47 grade II, 70 grade III, and 273 grade IV glioma patients (IDH1 mutation rate of 79%, 67%, and 5%, respectively). Overall, 56% of patients had seizures at presentation.
     We retrospectively identified 390 adult patients with pathologically confirmed grade II-IV glioma. Clinical data were compiled and pre and post-operative MRIs were reviewed. IDH1 status in all 390 tumors was determined by gene sequencing.
     Patients with IDH1 mutations (IDH1MUT) were significantly more likely to present with seizures than wild-type (IDH1WT) patients (68% vs 35%, p < 0.0001, n=390). When stratified by tumor location, IDH1 mutation was associated with increased seizures at presentation in patients with tumors involving only the frontal lobe (83% vs 53%, p=0.01, n=69). There was a non-significant trend for this association when stratified by other locations. In patients with high-grade gliomas, IDH1MUT was associated with increased seizures at presentation (58% vs 34% for IDH1WT, p=0.0005, n=343).
     This is a retrospective study.
     Patients with IDH1 mutant gliomas present more frequently with seizures compared to patients with IDH1 wild-type tumors.
     The association between IDH1 genotype and seizures may be dependent on tumor pathology but appears independent of tumor location. The contribution of IDH1 mutation and 2-HG to seizures in glioma patients warrant further investigation.


Project Roles:

A. Chou (), H. Ching (), S. Chang (), J. Carrillo (), S. Lalezari (), M. Spasic (), W. Choy (), A. Kim (), J. Selfridge (), J. Quan (), Y. Philippou (), J. Dye (), H. Soto (), D. Nagasawa (), G. Mathern (), R. Green (), I. Yang (), R. Prins (), A. Lai ()