Traumatic brain injury has a high morbidity and mortality in both civilian and military populations. Blast and other mechanisms of traumatic brain injury damage the brain by causing neurons to disconnect and atrophy. Such traumatic axonal injury can lead to persistently vegetative and minimally conscious states, for which extremely limited treatment options exist, including physical, occupational, speech and cognitive therapies. More than 50,000 patients have received vagus nerve stimulation for epilepsy and depression. In addition to decreased seizure frequency and severity, patients report enhanced mood, reduced daytime sleepiness independent of seizure control, increased slow wave sleep, and improved cognition, memory, and quality of life. Vagus nerve stimulation has not yet been performed in traumatic brain injured patients, however, animal experimentation has shown promising results. Early stimulation of the vagus nerve accelerates the rate and extent of behavioral and cognitive recovery after fluid percussion brain injury in rats. The purpose of this study is to demonstrate objective improvement in clinical outcome by placement of a vagus nerve stimulator in patients who are recovering from severe traumatic brain injury. Our hypothesis is that stimulation of the vagus nerve results in increased cerebral blood flow and metabolism in the forebrain, thalamus and reticular formation, which promotes arousal and improved consciousness, thereby improving outcome after traumatic brain injury resulting in minimally conscious or persistent vegetative states. If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed. We will achieve this objective by evaluating whether vagus nerve stimulation impacts clinical recovery from minimally conscious or persistent vegetative states caused by traumatic brain injury as assessed by the FIM"""""""" instrument and Functional Assessment Measure (FIM+FAM) as well as the JFK Coma Recovery Scale Score. We will also evaluate whether vagus nerve stimulation alters cerebral glucose metabolism as assessed by fluorodeoxyglucose positron emission tomography. Twelve patients will be enrolled in this initial crossover pilot study. These patients will have sustained a severe traumatic brain injury (Disability Rating Scale score of 22 to 29) between four and ten months from starting the study, and have no other concurrent active severe medical problems. Baseline EEG and magnetic resonance imaging (MRI) will be performed prior to vagus nerve stimulation implantation. Patients will be randomized to alternating three month periods with the device on or off. Outcomes will be assessed at three month intervals with the FIM"""""""" instrument and Functional Assessment Measure (FIM+FAM) and JFK Coma Recovery Scale by a neuropsychologist blinded to the status of the device. Positron emission tomography will also be performed. Patients will continue crossing over each three months and be followed for at least 18 months after enrollment. If vagus nerve stimulation is found to impact recovery, then a multicenter randomized prospective trial will be proposed to evaluate its efficacy.
Statement of Public Health Relevance Vagus nerve stimulation has not been performed in traumatic brain injured patients with decreased consciousness. If the patients in this study demonstrate improved recovery with vagus nerve stimulation, it will have a direct impact on their own wellness and quality of life. Ultimately the success of this proposal could profoundly improve the lives of not only brain-injured soldiers and their caregivers, but also the approximately 9,000 people per year in the United States alone who sustain a severe traumatic brain injury resulting in prolonged impaired consciousness.
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