Impact of Levetiracetam Treatment on 5-Aminolevulinic Acid Fluorescence Expression in IDH1 Wild-Type Glioblastoma

SIMPLE SUMMARY: The amino acid 5-aminolevulinic acid (5-ALA) is the benchmark regarding intraoperative imaging tools for glioblastoma (GB) surgery, and is known to facilitate the extent of resection, which results in an enhanced 6 month progression-free survival rate. Recent in vitro studies suggest that antiepileptic drugs (AEDs) result in a reduction in the fluorescence quality in gliomas. To date, there is no large clinical series investigating this issue in a homogeneous cohort. Approximately 25% of all GB patients have a symptomatic epilepsy as the initial symptom at presentation. Hence, this potential dilemma is of paramount importance. We found that the preoperative intake of levetiracetam is a significant risk factor for reduced intraoperative fluorescence in IDH1 wild-type GBs. We believe that this issue must be considered in future external validations, and physicians must carefully evaluate the indication of levetiracetam and avoid a prophylactic levetiracetam treatment in terms of the suspected diagnosis of glioblastoma. ABSTRACT: The amino acid 5-aminolevulinic acid (5-ALA) is the most established neurosurgical fluorescent dye and facilitates the achievement of gross total resection. In vitro studies raised concerns that antiepileptic drugs (AED) reduce the quality of fluorescence. Between 2013 and 2018, 175 IDH1 wild-type glioblastoma (GB) patients underwent 5-ALA guided surgery. Patients’ data were retrospectively reviewed regarding demographics, comorbidities, medications, tumor morphology, neuropathological characteristics, and their association with intraoperative 5-ALA fluorescence. The fluorescence of 5-ALA was graded in a three point scaling system (grade 0 = no; grade 1 = weak; grade 2 = strong). Univariable analysis shows that the intake of dexamethasone or levetiracetam, and larger preoperative tumor area significantly reduce the intraoperative fluorescence activity (fluorescence grade: 0 + 1). Multivariable binary logistic regression analysis demonstrates the preoperative intake of levetiracetam (adjusted odds ratio: 12.05, 95% confidence interval: 3.91–37.16, p = 0.001) as the only independent and significant risk factor for reduced fluorescence quality. Preoperative levetiracetam intake significantly reduced intraoperative fluorescence. The indication for levetiracetam in suspected GB should be carefully reviewed and prophylactic treatment avoided for this tumor entity. Future comparative trials of neurosurgical fluorescent dyes need a special focus on the influence of levetiracetam on fluorescence intensity. Further trials must validate our findings.