The IDH1 inhibitor ivosidenib improved seizures in a patient with drug-resistant epilepsy from IDH1 mutant oligodendroglioma

Compared to high grade gliomas, low grade gliomas such as oligodendrogliomas are often more epileptogenic. Epilepsy develops in 70–90% of patients with oligodendrogliomas and 40% of these are resistant to anti-seizure medications and surgery [3]. IDH1/2 mutation is one defining feature of oligodendrogliomas and confers improved prognosis when found in astrocytomas [7]. One possible etiology of the high rate of epileptogenicity in oligodendrogliomas is D-2-Hydroxyglutarate (D2HG), an oncometabolite seen in IDH mutation [8]. D2HG can mimic the effect of glutamate at the NMDA receptor and increase the seizure risk [11]. In this case report, we present a patient with drug resistant focal epilepsy from IDH1 mutant oligodendroglioma with markedly improved seizure frequency after starting Ivosidenib, an IDH1 inhibitor, in the absence of any changes to traditional anti-seizure medications. Our case suggests the possibility that IDH1 inhibitors may help reduce seizure burden in patients with difficult to control epilepsy from IDH1 mutant oligodendrogliomas. This is significant because we show that a targeted cancer therapy is able to improve seizure frequency through a unique pathway, and suggests that research into similar targeted, precision medicine therapies in brain lesions associated with epilepsy may be beneficial.