Vagus nerve stimulation to augment recovery from severe traumatic brain injury impeding consciousness: a prospective pilot clinical trial

Abstract

Objectives-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 limited treatment options exist, including physical, occupational, speech and cognitive therapies.More than 60,000 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.Early stimulation of the vagus nerve accelerates the rate and extent of behavioral and cognitive recovery after fluid percussion brain injury in rats.Methods-We recently obtained FDA approval for a pilot prospective randomized crossover trial 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.Discussion-If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed.

Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood–Brain Barrier Permeability following Experimental Traumatic Brain Injury

“…More recent studies have implicated vagus nerve activity, especially the efferent splenic component, in reducing systemic inflammation (Borovikova et al, 2000;Rosas-Ballina et al, 2008;Olofsson et al, 2012). Consistent with this, we have previously demonstrated that splenectomy markedly decreased TBI-triggered BBB permeability, suggesting a role for spleen-mediated systemic inflammation in BBB breakdown (Walker et al, 2010).…”

“…Breakdown of the BBB is an important secondary TBI pathology as it can cause further brain damage by allowing the infiltration of inflammatory cells and the uncontrolled access of circulating fluid, proteins, and signaling molecules to affected brain tissues (Tanno et al, 1992;Stahel et al, 2000;Zhao et al, 2007). These events exacerbate ongoing brain inflammation and can contribute to cerebral edema and increased intracranial pressure, leading to decreased cerebral blood flow, secondary tissue damage, brain herniation, and poor outcome (Raghupathi, 2004;Kochanek et al, 2015).…”

“…A number of studies have investigated brain inflammation in response to TBI and its contribution to BBB pathology (Sanderson et al, 1999;Morganti-Kossmann et al, 2002;Titus et al, 2013;de Rivero Vaccari et al, 2016). These studies have shown a shift in microglia polarization toward the proinflammatory M1 subtype, astrocyte activation, and increased production of inflammatory cytokines in the injured tissue (Loane et al, 2014;Turtzo et al, 2014).…”

“…These studies have shown a shift in microglia polarization toward the proinflammatory M1 subtype, astrocyte activation, and increased production of inflammatory cytokines in the injured tissue (Loane et al, 2014;Turtzo et al, 2014). Although increases in circulating levels of cytokines, including interleukin (IL)-1␤, IL-6, and tissue necrosis factor-␣ (TNF-␣), have been observed after TBI, a few studies have suggested that some of these molecules are released into the circulation from the injured brain Helmy et al, 2011).…”

Transcutaneous Auricular Vagus Nerve Stimulation on Neurological and Mental Disorders: From Germination to Future

“…In addition to the above mentioned, more and more results of taVNS on neurological and mental disorders was achieved including tinnitus [24,25], chronic migraine [26], schizophrenia [27,28], postoperative cognitive dysfunction [29]. clearance will be the first step in determining the efficacy of VNS for improvement of consciousness after severe brain injury [30]. Inspired by this, our team is focusing on transcutaneous auricular vagus nerve stimulation (taVNS) on patients with disorder of consciousness (DOC).…”