The blood-brain barrier (BBB) is a specialized interface allowing a unique environment for neuro-glia networks. BBB dysfunction is common in brain disorders. However, the mechanisms underlying BBB opening are poorly understood. The investigators suggest a novel mechanism modulating BBB integrity and therapeutic implications in patients with glioblastoma multiforme. The Transcranial Magnetic Stimulation (TMS) is a noninvasive method of stimulating cortical motor neurons through the scalp and skull capable of inducing electrical currents and depolarizing neurons in focal brain areas with the use of rapidly changing electromagnetic fields generated by a coil placed over the scalp. The objective of this study is to evaluate the safety and effects of the deep TMS (dTMS) on barrier integrity in 20 patients with malignant glial tumors (glioblastoma multiforme). BBB permeability will be quantified using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Permeability change will be compared between two DCE-MRI scans performed immediately after "real" and "sham" dTMS, randomly assigned within one week of each other.
Design of study: Randomized double-blind crossover study. Patients will present on two consecutive days in order to receive dTMS followed by DCE-MRI. Subjects will be randomized into two groups: the first group will be treated before with real-dTMS (the first day) and after with sham-dTMS (the second day); the second group will be treated before with sham-dTMS (the first day) and after with real-dTMS (the second day). At the end of each session of dTMS the patients will undergo by MRI exams.
Enrolled patients: twenty patients with glioblastoma multiforme treated with craniotomy and gross tumor resection or maximal debulking at least a year prior to the study and treated with standard post-operative radiotherapy and adjuvant chemotherapy.
dTMS will be delivered at 1 Hz, on the anterior periphery of the resected tumor bed using the Hesed-coil (H-coil) (Brainsway Ltd., Jerusalem, Israel). Sham stimulation will be delivered with a sham coil placed in the same helmet able to produce similar sounds and scalp sensations.
