Reduzierte Reaktivität in peritumoralem Gewebe gemessen mit TMS-EEG

Effects of brain tumors may extend far beyond the structural boarders of the mass, modifying activity of adjacent brain areas or even disrupting distant functional networks. Consequently, tumors that appear identical on imaging may be associated with different functional impairments and postoperative outcomes. TMS-EEG offers the unique potential to study these functional alterations by measuring the brains response to direct perturbations, while not relying on behavioral or motor outputs.

In this proof-of-concept case series we included five patients with high-grade gliomas (n=2), low-grade gliomas (n=2) or meningiomas (n=1) close to the midline before surgical resection of the tumor. Prior to TMS-EEG measurements, patients underwent a detailed neurological examination including assessment of motor and cognitive function. For TMS-EEG, three cortical points were targeted with approximately 200 TMS pulses each: one tumoral, one peritumoral and one matched contralateral control point. Stimulation intensity was defined based on the amplitude of early TMS-evoked potential (TEP) components (<50ms) in the contralateral control point and kept constant for the other sites. The TMS-associated click was masked with a tailored masking noise.

In three patients with gliomas, stimulation of the tumoral spot did not produce a functional TEP. In accordance with our hypothesis, the peritumoral stimulation produced a TEP dominated by a sleep-like low-complexity slow-wave suggesting dysconnectivity of the tissue. The fourth glioma patient presented with smaller, yet simple, sleep-like TEPs for both the tumoral and peritumoral spot. In all glioma patients, stimulation of the contralesional hemisphere led to a preserved, complex TEP. Interestingly, the meningioma patient had a preserved complex TEP for all stimulation sites, however alongside a reduced amplitude of the oscillations compared to healthy controls.

For the first time, we show that TMS-EEG can detect alterations of cortical reactivity in the perilesional tissue in patients with brain tumors. A more detailed assessment of these alterations can aid the quantification of a structural and functional reserve in patients before surgery by measuring the degree of network impairment. Importantly, this is independent of the functional network at question as the method does not require a behavioral readout during stimulation.