Association Between IDH1 and IDH2 Mutations and Preoperative Seizures in Patients with Low-Grade Versus High-Grade Glioma: A Systematic Review and Meta-Analysis

World Neurosurg. 2018 Mar:111:e539-e545. doi: 10.1016/j.wneu.2017.12.112. Epub 2017 Dec 27.


Background: Patients with brain tumors, particularly gliomas, commonly present with seizures. Higher incidence of seizure has been reported in low-grade gliomas and tumors located within the temporal and insular area. The association between IDH1 and IDH2 mutations with preoperative seizures in glioma and the magnitude of this association in low-grade versus high-grade gliomas are unclear. To clarify this relationship, a systematic review and meta-analysis was performed.

Methods: Following accepted guidelines and systematic review recommendations, electronic searches were performed in journal databases up to May 2017. Data were extracted and pooled via meta-analysis.

Results: We compared 782 patients with IDH1 and IDH2 mutations with 803 patients with wild-type IDH1 and IDH2 before surgery. There was a significant difference in seizure incidence between the IDH1 mutation group (61.6%) and wild-type IDH1 group (32.1%) (odds ratio 2.76; 95% confidence interval, 1.26-6.02; I2 = 73%; P = 0.01). Similar findings were observed in analysis of IDH1 and IDH2 mutations (odds ratio 2.74; 95% confidence interval, 1.74-4.33; I2 = 58%; P < 0.0001). The difference remained in both mutation groups (IDH1, IDH1 and IDH2) with grade II gliomas but not with grade III and IV gliomas. Patients with grade II gliomas showed a higher rate of IDH1 and IDH2 mutations and seizures than patients with grade III and IV gliomas.

Conclusions: This study demonstrated a significant association of IDH1 and IDH2 mutations with incidence of preoperative seizures. This association was significant only in patients with low-grade glioma (grade II) and not in patients with higher grade gliomas (grade III and IV).

Keywords: Glioma; Isocitrate dehydrogenase; Meta-analysis; Seizure.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Brain Neoplasms / epidemiology*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Gene Frequency
  • Glioma / epidemiology*
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Mutation / genetics*
  • Seizures / epidemiology*
  • Seizures / etiology
  • Seizures / genetics*


  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human