Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood-brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.

The use of transcranial motor-evoked potentials, somatosensory-evoked potentials and free-run electromyography for proper placement of paddle leads in chronic pain.

Introduction: As an alternative to those patients who cannot be performed an awake spinal cord stimulation (SCS) or had been percutaneously implanted with poor pain relief outcomes, neurophysiological monitoring through transcranial motor evoked potentials (MEPs), somatosensory-evoked potentials (SSEPs) and free-run electromyography (EMG) under general anesthesia allows the correct placement of surgical leads and provide objective responses.Methods: An initial series of 15 patients undergoing SCS implantation for chronic pain. Physiologic midline was determined with 32-channel NIM-Eclipse System equipment. During neurophysiological monitoring, MEPs, SSEPs, EMG and CMAPs were recorded.Results: MEPs, SSEPs, and EMG were able to target spinal cord physiological midline during SCS to all patients. Physiologic midline was deviated in 53% patients. No warning events in SSEPs, MEPs, or EMG were recorded in any patient.Conclusions: Bilateral CMAPs recording allows placement of paddle leads in physiological midline, obtaining an accurate coverage, pain relief and avoid unpleasant or ineffective stimulation postoperatively. While these neurophysiological techniques are generally used to provide information on the state of the nervous system and prevent neurological injury risks during SCS, our work has shown that can accurate direct lead placement.