IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low-grade gliomas

Objective: The isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most common mutation in World Health Organization (WHO) grade II gliomas, reported to be expressed in 70–80%, but only 5–10% of high grade gliomas. Low grade tumors, especially the protoplasmic subtype, have the highest incidence of tumor associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2‐hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a role in the pathogenesis of TAE in low grade gliomas. Methods: Thirty consecutive patients with WHO grade II gliomas were analyzed for the presence of the IDH1‐R132H mutation using immunohistochemistry. The expression of IDH1 mutation was semiquantified using open‐source biologic‐imaging analysis software. Results: The percentage of cells positive for the IDH1‐R132H mutation was found to be higher in patients with TAE compared to those without TAE (median and interquartile range (IQR) 25.3% [8.6–53.5] vs. 5.2% [0.6–13.4], p = 0.03). In addition, we found a significantly higher median IDH1 mutation expression level in the protoplasmic subtype of low grade glioma (52.2% [IQR 19.9–58.6] vs. 13.8% [IQR 3.9–29.4], p = 0.04). Significance: Increased expression of the IDH1‐R132H mutation is associated with seizures in low grade gliomas and also with the protoplasmic subtype. This supports the hypothesis that this mutation may play a role in the pathogenesis of both TAE and low grade gliomas