Seizures and high-grade gliomas: a UK single centre retrospective analysis

Abstract

High-grade gliomas (HGG) originate de novo (primary) or following transformation of a low-grade glioma (secondary), and can be considered as two different pathologies, influencing clinical behaviour. Despite this, both tumour types are currently managed similarly. Limited evidence exists investigating the two as separate entities in relation to seizure activity and biochemical markers, therefore forming the focus of our study. Retrospective analysis of 132 confirmed HGG cases in a single neurosciences centre. Variables recorded: patient demographics, tumour features (cytogenetics, location, primary or transformational, grade), seizure characteristics (type/onset), anti-epileptic drugs (AED) prescribed (prophylaxis/post-seizure) and operative intervention. 132 patients analysed: mean age at diagnosis 56 (range 21–82), 1.75:1 male:female, 48% males: 40% females experienced seizures. 105:27 primary:transformational HGG. Most common tumour location: frontal (38%) and temporal (23%). 30% HGG patients initially presented with seizures, 14% developed seizures post-diagnosis. 62/132 were prescribed AEDs; 84% post-seizure, 16% prophylactically. Compared to temporal lobe, frontal lobe HGG was a significant predictor of seizures (p<0.05). Transformational HGG was significantly more likely to present with seizures (p<0.05) compared to primary HGG (88%:58%). HGG with IDH1-IDH2 mutation was significantly more likely to present with seizures (p<0.05), with a 2:1 prevalence of IDH1-IDH2 mutation in transformational:primary. Right-sided HGG was significantly more likely to cause seizures (p<0.01). No significant difference was found between seizures and MGMT hypermethylation/1p-19q co-deletion. The differing HGG pathologies appear to influence the likelihood of developing seizures. Transformational HGG and the presence of IDH1-IDH2 mutation are associated with increased likelihood of seizure at presentation. Right-sided and frontal lobe HGG are associated with both increased seizures at presentation and overall occurrence. With further analysis of AED impact, this could potentially lead to a change in management of patients with HGG. However, conclusions drawn remain complicated by the limitations of a retrospective analysis.