# Increased cortical excitability to transcranial magnetic stimulation at the brain-tumor interface of IDH1-mutant gliomas

## TL;DR

This study shows that brain tumors with a specific mutation (IDH1) cause increased brain activity at their edges, which could lead to seizures and new treatment approaches.

## Contribution

The study provides first in vivo evidence that IDH1-mutant gliomas increase cortical excitability at the brain-tumor interface.

## Key findings

- IDH-mutant gliomas show increased cortical output at the brain-tumor interface compared to wildtype gliomas.
- Cortical hyperexcitability extends beyond the tumor border and is not explained by drug intake or other tumor features.

## Abstract

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.

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. Cortical excitability was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (ie, event-related spectral perturbation, ERSP) after TMS. The ERSP values were related to the IDH status, tumor grading, antiepileptic drug (AED) intake, and the spatial relationship to the tumor borders.

Within our sample, there was no significant group difference in RMT. The 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 with 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.

This study provides in vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas. The data demonstrate how molecular glioma characteristics affect peritumoral neuronal circuits. Modulating interactions at the BTI might pave the way for novel therapies.