Interventional Neurorehabilitation for Promoting Functional Recovery Post-Craniotomy: A Proof-of-Concept

ABSTRACT Purpose The human brain is a highly plastic ‘complex’ network –it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for ‘interventional neurorehabilitation’: connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. Methods In n=34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific Transcranial Magnetic Stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. Results 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and one-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. Conclusions For the first time, we demonstrate the safety profile and ability to recruit, enrol, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.