Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas

Abstract

OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training ("prehabilitation"), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27-37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function.

Keywords: ECSM = extraoperative cortical stimulation mapping; ICSM = intraoperative cortical stimulation mapping; brain plasticity; cCES = continuous cortical electrical stimulation; cortical stimulation; diagnostic and operative techniques; eloquent cortical areas; fMRI = functional MRI; glioma surgery; neurooncology; oncology; preservation of brain functions; rTMS = repetitive transcranial magnetic stimulation; sMRI = structural MRI.