Increased cortical excitability to transcranial magnetic stimulation at the brain-tumor interface of <i>IDH1</i> -mutant gliomas

Abstract Background There is increasing interest in the glioma-to-neuro communication at the brain-tumor-interface (BTI). In-vitro studies indicate that gliomas with a mutation of the isocitrate dehydrogenase (IDH) increase neuronal excitability of the peritumoral cortex contributing to epileptogenesis in these patients. However, in-vivo evidence is missing. This study evaluates the electric characteristics of the BTI relative to the IDH mutation status. Methods To investigate peritumoral cortical excitability (CE), we applied 5258 pulses of transcranial magnetic stimulation (TMS) at the BTI of IDH-mutant (IDH-mt) and IDH-wildtype (IDH-wt) glial tumors in 39 patients. CE was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (i.e., event-related spectral perturbation, ERSP) after TMS. ERSP values were related to the IDH status, tumor grading, antiepileptic drug intake (AED) and the spatial relationship to the tumor borders. Results Within our sample, there was not significant group difference in RMT. TMS to the BTI triggered an EMG synchronization decreasing linearly with the distance to the functional hotspot. In contrast, IDH-mt gliomas demonstrated an increased cortical output of the peritumoral brain tissue compared to IDH-wt gliomas. This effect was not attributable to AED intake or other histological and molecular characteristics. Notably, cortical hyperexcitability was detectable well beyond the tumor border. Conclusions This study provides in-vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas. The data demonstrates how molecular glioma characteristics affect peritumoral neuronal circuits. Modulating interactions at the BTI might pave the way for novel therapies.