gms | German Medical Science

Objective: Seizures in gliomas are especially common and well described in low grade gliomas. Still, also patients with high grade gliomas may suffer from seizures and here the underlying causes are poorly understood. Preclinical in vitro studies showed a role for SLC1A2, SLC38A3 and SLC7A11 in glioma-seizures. BCAT1 is critical for glioma cell proliferation by glutamate synthesis. We investigated the clinical and molecular relationship and differences in symptomatic and asymptomatic patients.

Methods: We performed a retrospective analysis of our clinical glioma database for clinical data from 2013 to 2014. Patients with glioblastoma multiforme were divided in symptomatic and asymptomatic for seizures. PCR was performed from tissue samples from both groups for SLC1A2, SLC38A3, SLC7A11 and BCAT1. MRI-scans were evaluated and tumor-volume and edema were calculated.

Results: 107 patients diagnosed glioblastoma in this period were identified. 23 patients were symptomatic with seizures (24.6%). All but one were IDH-1/2 wildtype. 2 gliomas were bilateral. Localization was 4 frontal, 9 temporal, 4 parietal, 1 occipital, 2 insular and 3 in the corpus callosum, respectively. Patients suffering seizures from high-grade gliomas showed to have significantly smaller tumors (p<0.03), which caused smaller edema (p<0.02) compared to asymptomatic tumors. SLC 38A1 and SLC7A11 were significantly upregulated in symptomatic tumors (p=0.0007 and p=0.0021, respectively) compared to asymptomatic tumors. BCAT1 expression was upregulated in symptomatic tumors (p=0.0013).

Conclusion: Patients suffering from high-grade glioma may present with seizures. In our cohort we could show that those patients present with significantly smaller tumors and less edema compared to asymptomatic patients. Seizures in high-grade glioma seem to be independent from IDH mutation status, which seems to be a main driver for seizures in low-grade glioma. The SLC 38A1 and SLC7A11 were upregulated in the symptomatic gliomas and hence could lead to an imbalance in glutamtate homeostasis. Upregulation of BCAT1 could lead to an oversupply of glutamate. Taken together, these findings could be an explanation for seizures in high-grade glioma. These data give a better understanding of patients with high-grade gliomas suffering from seizures.