Vagus Nerve Stimulation to Augment Recovery From Minimally Conscious or Persistently Vegetative States After Traumatic Brain Injury

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.

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.

The investigators 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. The investigators will also evaluate
whether vagus nerve stimulation alters resting and activational functional MRI.

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)
more than twelve 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 left 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. Outcomes will
also be assessed using quantitative eye movement tracking and functional magnetic resonance
imaging. Patients will cross over every 3 months and be followed for at least 18 months.