A 64-year-old right-handed male with the left temporal GBM presented to neurosurgery with expressive aphasia [Figure 2]. Patient 2 presented with expressive aphasia, generalized weakness, and gait disturbance to the ED 10 days following a very limited partial resection at an outside hospital. Outside brain CT demonstrated hemorrhage into the site of initial resection. Due to this patient's acutely worsening symptoms, the authors decided an aggressive surgical cytoreduction approach to be the most beneficial option for the patient. On preoperative evaluation, he exhibited mild right pronator drift, apraxia, expressive aphasia, and wide-based gait with decreased cadence. Following surgery, postoperative imaging was obtained [Figure 2]. Before cTBS administration, physical therapy evaluation was significant for improved gait and activity tolerance, but increased word finding difficulty, decreased left lower extremity strength graded 4/5, and right dysmetria. This ipsilateral weakness was likely due to postoperative edema leading to compression of the right corticospinal tract at the level of the tumor resection, thereby causing left lower extremity weakness. The patient's mild right pronator drift and apraxia were unchanged from preoperative evaluation. Medications affecting seizure threshold that was given during a patient's hospital course are listed with dosage and time of administration when applicable in [Table 3].
Postoperative rfMRI was obtained in both patients to identify networks through ICA and to target cTBS therapy contralateral to the network nodes associated with the most significant postoperative deficit. The resting-state functional data were preprocessed using the Multivariate Exploratory Linear Decomposition into Independent Components application of the FSL toolbox v. 5.0 (www.fmrib.ox.ac.uk/fsl). The images were smoothed with a Gaussian kernel of full width at half maximum of 8 mm. A slice timing correction was used to correct for the different acquisition times. The data were then preprocessed with high-pass temporal filtering (cutoff of 100 s) and with the removal of nonbrain structures from the echo planar imaging volumes (brain extraction tool). A threshold of 0.66 was used to eliminate extraneous noise within brain networks. All independent components were reviewed to identify distinct brain networks. The resulting ICA threshold maps were displayed on the patient's postoperative anatomical MRI using the Multi-image Analysis GUI (Mango) 4.0.1 (ric.uthscsa.edu/mango). We identified brain networks pertinent to postoperative deficits specific to each patient, based on previous literature regarding anatomic location and published functional activation maps.
For patient 1, we targeted the motor network through right primary motor cortex (M1) with one session of cTBS. Due to her most recent seizure being 2 weeks before presentation for surgery, lack in severity of deficits, and length of stay, the patient received only one treatment. Our goal with initiation of this intervention was to safely restore motor network function and improve her right hemiparesis by decreasing the contralateral inhibitory effect of M1. Studies examining cTBS for poststroke rehabilitation have revealed the utility of downregulating excitability in the intact hemisphere to improve paresis. The basis of this mechanism has been explored in studies with healthy volunteers, which demonstrate cTBS decreases the excitability of the stimulated motor cortex and increases excitability of the contralateral motor cortex. This altered excitability results in the potential for improved motor function of the impaired appendage.
Patient 2 demonstrated worsening expressive aphasia postoperatively. Therefore, we attempted to target the language network by stimulating the right inferior frontal gyrus (IFG). The overall goal of this approach was to restore language network function by reducing cortical excitability of the contralesional IFG, thereby reducing severity of the expressive aphasia deficit. Despite initial theories of speech and language production being lateralized to the left hemisphere, it has been shown to have similarities to the motor network requiring input and execution from both hemispheres. Our aim was to improve patient 2's language function by inhibiting the intact hemisphere to allow improved or more equal coupling of reception and production of information due to the requirement of bilateral transformation.
Independent components were loaded into the TMS platform (Magventure MagPro 100x). Each patient's anatomic image was uploaded as a NIFTI file and then the ICA map at threshold was overlaid to facilitate navigation of the TMS coil to the targeted network node. TMS planning on Localite TMS Navigator Version 3.0.48 (Localite TMS Navigator, Localite, Sankt Augustin, Germany) was initiated, and both the target and entry point were selected to allow guidance of the TMS coil and direction of the current [Figure 3]. aMT was found by stimulating the right M1 and causing a visible twitch in flexor digitorum interossei and abductor pollicis brevis. Notably, both patients had left-sided lesions; therefore, right M1, contralateral to the lesion, was stimulated to find aMT.
Navigated cTBS was administered with a MagVenture MagPro device using a Figure 8 coil at bedside in the ICU for both patients. Patient 1 received one session of 5 Hz cTBS targeted to right M1 at 80% of aMT for a total of 200 pulses. This intervention was administered about 28 h following surgery. Patient 2 received three sessions of 5 Hz cTBS to right IFG at 80% of aMT for a total of 600 pulses, 48 h postoperatively.