Tumor-associated epilepsy at diagnosis in glioblastoma patients reveals an inflammatory molecular signature and is associated with better overall survival.

Authors

Lilyana Dimova, Jenny Stritzelberger, Diyan Dimov, Jonas Ort, Hussam Aldin Hamou, Hans Clusmann, Oliver Schnell, Hajo Hamer, Florian Putz, Stefanie Corradini, Ludwig Singer, Arnd Dörfler, Franz Ricklefs, Richard Drexler, Matthias Simon, Dieter Henrik Heiland, Daniel Delev

Published in

Neuro-oncology. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Glioblastoma (GB) is the most aggressive primary brain tumor in adults. Tumor-associated epilepsy at diagnosis (TAE) is common, yet its prognostic significance remains unclear.
We analyzed a retrospective multicenter test cohort of 855 GB patients (Aachen, Hamburg, Bielefeld) and validated findings in a prospectively collected cohort of 344 patients (Erlangen). Survival was assessed using multivariable Cox regression, propensity score matching, and interaction modeling of TAE and extent of resection (EOR). Molecular profiling included methylation-based classification, epigenetic deconvolution, and spatial transcriptomics.
TAE was independently associated with improved survival (HR 0.81, 95% CI 0.69-0.99, P = .036, absolute survival advantage ∼4-5 months). This effect was validated in the independent cohort (C-index 0.68 (95% CI 0.62-0.74) and persisted in propensity-matched analyses (HR 0.74, 95% CI 0.56-0.96, P = .027). Interaction modeling revealed that gross total resection (GTR) improved survival in both groups but particularly in patients with TAE (EOR interaction HR 0.69, 95% CI 0.49-0.99, P = .041). In this subgroup, partial resection provided no significant advantage over biopsy, whereas patients without seizures benefited incrementally from both partial resection and GTR. Molecular analysis demonstrated enrichment of the RTK II subtype, differentiated cell states, and an inflammatory microenvironment in glioblastoma with TAE; tumors without seizures displayed neuronal and stem-like features. Functional validation using Electrogenomics showed that glioblastoma cortical slices with increased inflammatory score exhibited synchronization of action potentials characteristic for seizure-like epileptiform activity.
TAE at diagnosis is a favorable prognostic marker in GB, defining a biologically distinct subgroup. Seizure status modifies the prognostic effect of surgical resection, underscoring the importance of GTR particularly in patients presenting with TAE.

PMID:
42320046
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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