Louise-Bender Pape et al. examined the safety and restorative effects of rTMS by attempting to restore consciousness following a severe TBI. They used rTMS to induce neurobehavioral changes in a 26-year-old male who remained in a vegetative state 287 days after a severe TBI. Computerized tomography (CT) scans revealed hemorrhage in the right temporal lobe as well as diffuse traumatic subarachnoid hemorrhage. The patient was described to be in a state of arousal without behavioral evidence of awareness of self or capacity to interact with the environment [Disorders of Consciousness Scale (DOCS) = 50.3]. Prior to treatment, the patient was titrated off neurostimulants (amantadine and methylphenidate) and antispasticity medications and did not receive any neurological medication during the course of the intervention. Safety was ensured by administering a modified lower-than-normal frequency rTMS protocol following completion of a daily medical examination, with an electroencephalogram (EEG) conducted before and after each session and continued bi-weekly for 6 weeks post-treatment. Stimulation was administered to the right DLPFC at 110% abductor pollicis brevis MT (300 trains/session with a 5 s inter-train interval, where each train consisted of a paired-pulse with a 100 ms inter-pulse interval) for 6 weeks. The patient experienced complications that the authors concluded were not related to the rTMS intervention. The patient was treated with 2 g Ceftazidime, 1 g vancomycin, 900 mg amikacin, and 500 mg Cipro. No adverse effects were reported as a result of rTMS treatment, and EEGs performed throughout and following the treatment revealed lack of epileptiform discharges following rTMS. The authors report a change in classification of state of consciousness from vegetative state to minimally conscious (DOCS: 15th session = 58.6; 30th = 53.7; 6 weeks post-treatment = 56.7). Qualitative improvements through the course of rTMS were reported, including markedly improved motor skills and visual ability, the appearance of vocalizations, and the development of basic communication. Continued qualitative improvements were reported a year following rTMS treatment by the patient's family, with no reported adverse events.
Manganotti and colleagues administered high-frequency rTMS to three patients with severe brain injuries due to TBI. Two patients were classified as minimally conscious, while the third was in a vegetative state. Safety criteria included absence of contraindication to rTMS, stability of vital parameters, and more than 12 months since injury. A single session was administered to the primary motor cortex at 100% MT (20 Hz, 1000 pulses/session; 5 s train duration, 20 s inter-train interval) for 10 trains. A clinical response was not witnessed in any of the three patients, with EEG demonstrating no reaction to brain stimulation and a decrease in MT. No adverse effects or seizures were reported.
Similarly, Giovannelli and colleagues reported no clinically significant neurobehavioral change following rTMS therapy for two patients in a vegetative state due to TBI. Using a randomized, double-blind cross-over design with a sham stimulation control, high-frequency rTMS was applied to the left M1 at 60% stimulator output (20 Hz or sham; 1000 pulses/session) for five consecutive days. The patients did not demonstrate statistically significant improvement compared to sham stimulation as measured using the JFK Coma Recovery Scale-Revised (CRS-R) and Clinical Global Impression (CGI) rating.