Prehabilitation and rehabilitation using data-driven, parcel-guided transcranial magnetic stimulation treatment for brain tumor surgery: proof of concept case report

Improved knowledge of the neuroplastic potential of the brain connectome has facilitated the advancement of neuromodulatory treatments for brain tumor patients especially in the perioperative period. More recently, the idea of inducing neuroplastic changes before surgery as “prehabilitation” has been suggested in low-grade gliomas with favorable data. However, it is uncertain the degree to which this treatment with transcranial magnetic stimulation (TMS) would benefit patients with high-grade gliomas, especially with additional rehabilitation after surgery and targets defined by personalized connectomic data. The current report details a case of a patient with recurrent glioblastoma in the right motor area 2 years after previous total resection. Given the desire for a more aggressive recurrent surgery in a highly functional area, the authors decided to proceed with “prehabilitation” by stimulating the surrounding motor cortices around the lesion to turn down the motor cortex connectivity before the recurrent surgery and then completing “rehabilitation” after the surgery. Structural-functional connectomic analyses were completed using Infinitome software based on an individualized patient brain atlas using machine-learning based parcellations. Repetitive TMS was employed, specifically using continuous and intermittent theta burst stimulation protocols. Prehabilitation consisted of using continuous theta burst stimulation at the estimated surgical entry point parcel and intermittent theta burst stimulation at adjacent parcellations for a total of 10 days with 5 sessions per day per target leading up until the surgery. A gross-total resection was obtained, but the patient woke up with left-sided hemiparesis. Resting-state functional magnetic resonance imaging derived connectivity demonstrated a case of a primarily pure cingulate-motor resection causing hemiplegia with an intact corticospinal tract and supplementary motor area. Functional connectivity outliers in cingulate-motor parcels were identified and compared with connectivity matrices from a healthy control atlas. Anomalies, parcels defined as functioning significantly outside a normal range, were chosen as rehabilitation TMS targets to be similarly treated for a total of 10 days with 5 sessions per day per target approximately two weeks after surgery. By using continuous theta burst stimulation on hyperconnected parcels and intermittent theta burst stimulation on hypoconnected parcels, the patient demonstrated significant motor improvement with only 4+/5 strength in the left arm 1 month after surgery. This report demonstrates for the first time the feasibility of using TMS treatment for glioblastoma surgery near “eloquent” cortices as a means of prehabilitation before surgery and rehabilitation after surgery. This parcel-guided approach for TMS treatment based on the cortical site of entry and individualized connectivity analyses allowed for maximal tumor resection and minimal long-term neurologic deficits.