Effects of Levetiracetam and Lacosamide on survival and seizure control in IDH-wild type glioblastoma during temozolomide plus radiation adjuvant therapy

Introduction: There are no clear indications for the best choice of anti-seizure medications to control brain tumor related epilepsy. In vitro studies have shown an antitumoral effect of Levetiracetam and Lacosamide on glioblastoma IDH-wild type. Research question: This study investigates whether the use of levetiracetam and/or lacosamide impacts survival rates. The secondary aim was to evaluate the efficacy of both ASMs in controlling seizures. Materials and methods: In this observational retrospective single-cohort study, patients underwent chemoradiation protocol after GBM surgery. They were grouped as follows: (1) use of levetiracetam, (2) use of lacosamide, (3) simultaneous use of levetiracetam and lacosamide, (4) no ASM usage. Survival curves were plotted using the Kaplan-Meier method coupled with a log-rank test for difference assesments. To evaluate the pharmacological efficacy of post-operative seizure control, a negative binomial regression was conducted. Results: The study included 272 patients, 174 of which underwent adjuvant chemoradiation treatment. Patients without ASM therapy had a non-significant longer median OS (compared to the other groups (log-rank = 0.37). The IRR of seizure relapse was 2.57 (p = 0.007) times higher in lacosamide users, and MGMT promoter methylation demonstrated a protective effect against postoperative seizure onset (p = 0.05), regardless of the aforementioned confounding factors. Discussion and conclusions: In patients diagnosed with GBM IDH-WT undergoing chemoradiation therapy, the use of levetiracetam or lacosamide for controlling BTRE does not seem to modify survival. Lacosamide users exhibited a higher IRR of postoperative seizures compared to levetiracetam users, and MGMT promoter methylation appears to be a protective factor

Resolving the EPR Spectra in the Cytochrome bc (1) Complex from Saccharomyces cerevisiae

Quinone molecules are ubiquitous in living organisms. They are found either within the lipid phase of the biological membrane (quinone pool) or are bound in specific binding sites within membrane-bound protein complexes. The biological function of such bound quinones is determined by their ability to be reduced and/or oxidized in two successive one-electron steps. As a result, quinones are involved as one- or two-electron donors or acceptors in a large number of biological electron-transfer steps occurring during respiratory or photosynthetic processes. The intermediate formed by a one-electron reduction step is a semiquinone, which is paramagnetic and can be studied by electron paramagnetic resonance (EPR) spectroscopy. Detailed studies of such states can provide important structural information on these intermediates in such electron-transfer processes. In this study, we focus on the redox-active ubiquinone-6 of the yeast cytochrome bc (1) complex (QCR, ubiquinol: cytochrome c oxidoreductase) from Saccharomyces cerevisiae at the so-called Q(i) site. Although the location of the Q(i) binding pocket is quite well known, details about its exact binding are less clear. Currently, three different X-ray crystallographic studies suggest three different binding geometries for Q(i). Recent studies in the bacterial system (Rhodobacter sphaeroides) have suggested a direct coordination to histidine as proposed in the chicken heart crystal structure model. Using the yeast system we apply EPR and especially relaxation filtered hyperfine (REFINE) spectroscopy to study the Q(i) binding site. N-14-electron spin-echo envelope modulation spectroscopy together with an inversion-recovery filter (REFINE) is applied to resolve the question of whether N-14 modulations arise from interactions to Q (i) (center dot-) or to the Rieske iron-sulphur center. These results are discussed with regard to the location and potential function of Q(i) in the enzyme