Tracking evolving cortical plasticity in recurrent low-grade glioma patients: a prospective pilot study based on serial intraoperative awake direct electrostimulation and transcranial magnetic stimulation mappings.

Abstract

In patients with low-grade gliomas (LGGs), reallocations of cortical functions (i.e., plasticity) evolve over the course of the disease, allowing serial resections while preserving patients' neurological status. This study aimed to capture evolving patterns of LGG-induced plasticity by means of longitudinal measures of cortical functions based on serial intrasurgical direct electrical stimulation (DES) mappings and navigated transcranial magnetic stimulation (nTMS) mapping. It further assessed nTMS prediction accuracy using DES measures as a reference. In patients with confirmed LGG, cortical functional remodeling was assessed through initial intraoperative awake DES mapping (DESI) and DES remapping (DESII), typically spaced several years apart. An additional session of nTMS mapping mirroring intrasurgical functional testing was performed before DESII. In particular, nTMS mapping was guided by preexistent DESI functional maps to maximize stimulation coverage in areas susceptible to presenting with functional reorganizations. Probabilistic functional maps accounting for functional and nonfunctional responses were computed through a multistep voxelwise approach to measure cortical reallocations between DESI and DESII and nTMS prediction accuracy. Eight patients were prospectively enrolled (median DESI-DESII time interval 7.0 years). Overall, 2268 nTMS and 244 DES cortical sites were recorded. DESII systematically highlighted evolving plasticity. The nTMS functional convergence index, based on comparisons with DESII results, was heterogeneous across cortical structures. Converging nTMS/DESII measures were associated with nonfunctional nTMS responses (91.13%). Evolving patterns of plasticity were effectively revealed by nonfunctional nTMS mapping, except within the ventral premotor cortex (vPMC). Further, nTMS prediction accuracy was high within the pars triangularis, supramarginal gyrus, and supplementary motor area (R2 = 0.50) and low within the vPMC (R2 = 0.0005). These results provide a unique overview of evolving patterns of cortical plasticity in LGG patients. Although nTMS may help provide longitudinal metrics of plasticity in brain tumor patients, several challenges must be addressed before routine clinical applications.