New treatments in traumatic brain injury: A clinical trial of repetitive transcranial magnetic stimulation

By Reza Ehsanian, MD, PhD

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide [1]. According to the Centers for Disease Control and Prevention (CDC), in 2010 there were approximately 2.5 million emergency department visits, hospitalizations, and deaths due to TBI in the U.S. alone. In 2015, the CDC estimated that approximately 16% of annual hospitalizations due to traumatic injury were related to TBI [2]. A substantial cost results from TBI, as there were 21.4 billion dollars in charges for TBI-related admissions in 2010 and 8.2 billion dollars in charges for ED visits [3]. Severe TBI is particularly devastating [4, 5], but for the families and patients remaining in states of disordered consciousness following severe TBI there may be hope. There is mounting literature that cortical processing can occur even while patients are unconscious, and evidence of late recoveries continues to accumulate, suggesting that disordered consciousness is a potentially modifiable condition [6–11].

A paucity of treatments exists to induce or accelerate functional and adaptive recovery for individuals with severe TBI [12–14]. Current neurorehabilitation strategies for individuals with disordered consciousness involves sensory stimulation and pharmacotherapies, such as amantadine [11, 15]. Researchers are actively investigating other potential treatment modalities for those suffering from disordered consciousness after a TBI. Over the past two years I have had the honor of being part of an exceptional team of physicians and scientists trying to investigate a targeted treatment, repetitive transcranial magnetic stimulation (rTMS), as part of a clinical trial (NCT02366754) titled “rTMS: A Treatment to Restore Function after Severe TBI”. The purpose of the trial is to investigate the therapeutic effectiveness of rTMS by studying the functional and structural neural changes that occur post-rTMS. The rTMS protocol employed in the clinical trial is based on pilot data collected from 3 participants. Despite poor recovery likelihood, all three pilot participants made neurobehavioral gains during rTMS and each maintained these gains at follow-up. Although an incidence of seizure activity was apparent in one pilot subject, the safety data from the pilot subjects largely confirms a lack of adverse events related to rTMS [16].

For further information on the study, its locations, and the sponsors and collaborators, please visit:

Reza Ehsanian, MD, PhD

Reza Ehsanian, MD, PhD is a PM&R Resident at Stanford University and 2017–2018 Research Representative to the Resident Fellow Council of the Association of Academic Physiatry.


1. Leo, P. and M. McCrea, Epidemiology, in Translational Research in Traumatic Brain Injury, D. Laskowitz and G. Grant, Editors. 2016: Boca Raton (FL).

2. Report to Congress on Traumatic Brain Injury in the United States: Epidemiology and Rehabilitation, C.f.D.C. Prevention, Editor. 2015, Centers for Disease Control and Prevention: Atlanta, GA.

3. Marin, J.R., M.D. Weaver, and R.C. Mannix, Burden of USA hospital charges for traumatic brain injury. Brain Inj, 2017. 31(1): p. 24–31.

4. Kayani, N.A., et al., Health and economic burden of traumatic brain injury: Missouri, 2001–2005. Public Health Rep, 2009. 124(4): p. 551–60.

5. Relyea-Chew, A., et al., Personal bankruptcy after traumatic brain or spinal cord injury: the role of medical debt. Arch Phys Med Rehabil, 2009. 90(3): p. 413–9.

6. Menon, D.K., et al., Cortical processing in persistent vegetative state. Wolfson Brain Imaging Centre Team. Lancet, 1998. 352(9123): p. 200.

7. Moritz, C.H., et al., Functional MR imaging assessment of a non-responsive brain injured patient. Magn Reson Imaging, 2001. 19(8): p. 1129–32.

8. Owen, A.M. and M.R. Coleman, Detecting awareness in the vegetative state. Ann N Y Acad Sci, 2008. 1129: p. 130–8.

9. Schiff, N.D., et al., fMRI reveals large-scale network activation in minimally conscious patients. Neurology, 2005. 64(3): p. 514–23.

10. Fernandez-Espejo, D. and A.M. Owen, Detecting awareness after severe brain injury. Nat Rev Neurosci, 2013. 14(11): p. 801–9.

11. Giacino, J.T., et al., Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med, 2012. 366(9): p. 819–26.

12. Pape, T.L., et al., Preliminary framework for Familiar Auditory Sensory Training (FAST) provided during coma recovery. J Rehabil Res Dev, 2012. 49(7): p. 1137–52.

13. Lancioni, G.E., et al., An overview of intervention options for promoting adaptive behavior of persons with acquired brain injury and minimally conscious state. Res Dev Disabil, 2010. 31(6): p. 1121–34.

14. Consensus conference. Rehabilitation of persons with traumatic brain injury. NIH Consensus Development Panel on Rehabilitation of Persons With Traumatic Brain Injury. JAMA, 1999. 282(10): p. 974–83.

15. Zafonte, R., et al., Pharmacotherapy to enhance arousal: what is known and what is not. Prog Brain Res, 2009. 177: p. 293–316.

16. Pape TLB, Rosenow JM, Patil V, Steiner M, Harton B, Guernon A, Herrold A, Pacheco M, Crisan E, Ashley WW Jr, Odle C, Park Y, Chawla J, Sarkar K. (2014) rTMS safety for two subjects with disordered consciousness after traumatic brain injury. Brain Stimulation, 7(4):620–622.