Isocitrate dehydrogenase mutations: A biomarker for glioma-related excitability and seizures

Tumor-related epilepsy (TRE) is common in patients with gliomas (40%–70%) and carries a substantial degree of morbidity and mortality.1,2 The impetus to understand the pathophysiology of TRE has led to the identification of several tumor markers that are associated with increased risk of seizures. Tumor-mediated glutamate release is one proposed mechanism that has more recently gained traction.3,4 Another tumor marker that has attracted the attention of researchers is expression of mutated isocitrate dehydrogenase 1 (IDH1mut), an enzyme whose normal function is key to the Kreb cycle; the nonmutated enzyme catalyzes the conversion of isocitrate to α-ketoglutarate. IDH1mut is an accepted diagnostic biomarker for secondary glioblastomas that is associated with improved survival.5 In its mutated form, IDH1mut reduces α-ketoglutarate to d-2-hydroxyglutarate (D2HG). Structural similarities between D2HG and glutamate have promoted the theory that overproduction of D2HG could mechanistically play a role in neuronal excitation in the glial tumor model. Thus far, the association between mutant IDH expression and epilepsy has been disputed in the work of previous groups.6,7
Source: Neurology - Category: Neurology Authors: Tags: All Clinical trials, Primary brain tumor, All Epilepsy/Seizures EDITORIALS Source Type: research