Case report: Continuous spinal cord physiologic monitoring following traumatic spinal cord injury-A report from the Winnipeg Intraspinal Pressure Study (WISP).

Introduction: Acute traumatic spinal cord injury is routinely managed by surgical decompression and instrumentation of the spine. Guidelines also suggest elevating mean arterial pressure to 85 mmHg to mitigate secondary injury. However, the evidence for these recommendations remains very limited. There is now considerable interest in measuring spinal cord perfusion pressure by monitoring mean arterial pressure and intraspinal pressure. Here, we present our first institutional experience of using a strain gauge pressure transducer monitor to measure intraspinal pressure and subsequent derivation of spinal cord perfusion pressure. Case presentation: The patient presented to medical attention after a fall off of scaffolding. A trauma assessment was completed at a local emergency room. He did not have any motor strength or sensation to the lower extremities. A computed tomography (CT) scan of the thoracolumbar spine confirmed a T12 burst fracture with retropulsion of bone fragments into the spinal canal. He was taken to surgery for urgent decompression of the spinal cord and instrumentation of the spine. A subdural strain gauge pressure monitor was placed at the site of injury through a small dural incision. Mean arterial pressure and intraspinal pressure were then monitored for 5 days after surgery. Spinal cord perfusion pressure was derived. The procedure was performed without complication and the patient underwent rehabilitation for 3 months where he regained some motor and sensory function in his lower extremities. Conclusion: The first North American attempt at insertion of a strain gauge pressure monitor into the subdural space at the site of injury following acute traumatic spinal cord injury was performed successfully and without complication. Spinal cord perfusion pressure was derived successfully using this physiological monitoring. Further research efforts to validate this technique are required.

Utility of Transcranial Doppler in Moderate and Severe Traumatic Brain Injury: A Narrative Review of Cerebral Physiologic Metrics.

Since its creation in the 1980s, transcranial Doppler (TCD) has provided a method of non-invasively monitoring cerebral physiology and has become an invaluable tool in neurocritical care. In this narrative review, we examine the role TCD has in the management of the moderate and severe traumatic brain injury (TBI) patient. We examine the principles of TCD and the ways in which it has been applied to gain insight into cerebral physiology following TBI, as well as explore the clinical evidence supporting these applications. Its usefulness as a tool to non-invasively determine intracranial pressure, detect post-traumatic vasospasm, predict patient outcome, and assess the state of cerebral autoregulation are all explored.

Near-Infrared Cerebrovascular Reactivity for Monitoring Cerebral Autoregulation and Predicting Outcomes in Moderate to Severe Traumatic Brain Injury: Proposal for a Pilot Observational Study.

BACKGROUND: Impaired cerebrovascular reactivity after traumatic brain injury (TBI) in adults is emerging as an important prognostic factor, with strong independent association with 6-month outcomes. To date, it is unknown if impaired cerebrovascular reactivity during the acute phase is associated with ongoing impaired continuously measured cerebrovascular reactivity in the long-term, and if such measures are associated with clinical phenotype at those points in time. OBJECTIVE: We describe a prospective pilot study to assess the use of near-infrared spectroscopy (NIRS) to derive continuous measures of cerebrovascular reactivity during the acute and long-term phases of TBI in adults. METHODS: Over 2 years, we will recruit up to 80 adults with moderate/severe TBI admitted to the intensive care unit (ICU) with invasive intracranial pressure (ICP) monitoring. These patients will undergo high-frequency data capture of ICP, arterial blood pressure (ABP), and NIRS for the first 5 days of care. Patients will then have 30 minutes of noninvasive NIRS and ABP monitoring in the clinic at 3, 6, and 12 months post-injury. Outcomes will be assessed via the Glasgow Outcome Scale and Short Form-12 questionnaires. Various relationships between NIRS and ICP-derived cerebrovascular reactivity metrics and associated outcomes will be assessed using biomedical signal processing techniques and both multivariate and time-series statistical methodologies. RESULTS: Study recruitment began at the end of February 2020, with data collection ongoing and three patients enrolled at the time of writing. The expected duration of data collection will be from February 2020 to January 2022, as per our local research ethics board approval (B2018:103). Support for this work has been obtained through the National Institutes of Health (NIH) through the National Institute of Neurological Disorders and Stroke (NINDS) (R03NS114335), funded in January 2020. CONCLUSIONS: With the application of NIRS technology for monitoring of patients with TBI, we expect to be able to outline core relationships between noninvasively measured aspects of cerebral physiology and invasive measures, as well as patient outcomes. Documenting these relationships carries the potential to revolutionize the way we monitor patients with TBI, moving to more noninvasive techniques. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18740.

The Impact of Mean Arterial Pressure on Functional Outcome Post Trauma-Related Acute Spinal Cord Injury: A Scoping Systematic Review of the Human Literature.

PURPOSE: To perform a scoping systematic review on the literature surrounding mean arterial pressure (MAP) and functional outcomes post traumatic acute spinal cord injury (ASCI). METHODS: We performed a systematic review of the literature via searching MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to January 2015. We also performed a handsearch of various published meeting proceedings. Through a 2-step review process, employing 2 independent reviewers, we selected articles for the final review based on predefined inclusion/exclusion criteria. RESULTS: Nine studies were included in the final review. Only 2 were prospective studies. All studies documented some degree of objective functional outcome in relation to MAP posttraumatic ASCI. Four studies documented a relation between higher MAP and improved functional outcome. Five studies failed to show any relationship between MAP and functional outcome. CONCLUSIONS: Although no definitive conclusions could be reached based on the data collected, this study does give valuable insight into future avenues of research on the topic of hemodynamic management in traumatic ASCI as well as provides guidelines for refinement of future study design.

Monitoring the Neuroinflammatory Response Following Acute Brain Injury.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are major contributors to morbidity and mortality. Following the initial insult, patients may deteriorate due to secondary brain damage. The underlying molecular and cellular cascades incorporate components of the innate immune system. There are different approaches to assess and monitor cerebral inflammation in the neuro intensive care unit. The aim of this narrative review is to describe techniques to monitor inflammatory activity in patients with TBI and SAH in the acute setting. The analysis of pro- and anti-inflammatory cytokines in compartments of the central nervous system (CNS), including the cerebrospinal fluid and the extracellular fluid, represent the most common approaches to monitor surrogate markers of cerebral inflammatory activity. Each of these compartments has a distinct biology that reflects local processes and the cross-talk between systemic and CNS inflammation. Cytokines have been correlated to outcomes as well as ongoing, secondary injury progression. Alongside the dynamic, focal assay of humoral mediators, imaging, through positron emission tomography, can provide a global in vivo measurement of inflammatory cell activity, which reveals long-lasting processes following the initial injury. Compared to the innate immune system activated acutely after brain injury, the adaptive immune system is likely to play a greater role in the chronic phase as evidenced by T-cell-mediated autoreactivity toward brain-specific proteins. The most difficult aspect of assessing neuroinflammation is to determine whether the processes monitored are harmful or beneficial to the brain as accumulating data indicate a dual role for these inflammatory cascades following injury. In summary, the inflammatory component of the complex injury cascade following brain injury may be monitored using different modalities. Using a multimodal monitoring approach can potentially aid in the development of therapeutics targeting different aspects of the inflammatory cascade and improve the outcome following TBI and SAH.

Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review.

BACKGROUND: The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term "effective half-life" (t1/2) in order to describe the "fall" rate in serum. MATERIALS AND METHODS: Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. RESULTS: Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1-2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24-48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. CONCLUSION: Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.

Acetylcholinesterase from the invertebrate Ciona intestinalis is capable of assembling into asymmetric forms when co-expressed with vertebrate collagenic tail peptide.

To learn more about the evolution of the cholinesterases (ChEs), acetylcholinesterase (AChE) and butyrylcholinesterase in the vertebrates, we investigated the AChE activity of a deuterostome invertebrate, the urochordate Ciona intestinalis, by expressing in vitro a synthetic recombinant cDNA for the enzyme in COS-7 cells. Evidence from kinetics, pharmacology, molecular biology, and molecular modeling confirms that the enzyme is AChE. Sequence analysis and molecular modeling also indicate that the cDNA codes for the AChE(T) subunit, which should be able to produce all three globular forms of AChE: monomers (G(1)), dimers (G(2)), and tetramers (G(4)), and assemble into asymmetric forms in association with the collagenic subunit collagen Q. Using velocity sedimentation on sucrose gradients, we found that all three of the globular forms are either expressed in cells or secreted into the medium. In cell extracts, amphiphilic monomers (G(1)(a)) and non-amphiphilic tetramers (G(4)(na)) are found. Amphiphilic dimers (G(2)(a)) and non-amphiphilic tetramers (G(4)(na)) are secreted into the medium. Co-expression of the catalytic subunit with Rattus norvegicus collagen Q produces the asymmetric A(12) form of the enzyme. Collagenase digestion of the A(12) AChE produces a lytic G(4) form. Notably, only globular forms are present in vivo. This is the first demonstration that an invertebrate AChE is capable of assembling into asymmetric forms. We also performed a phylogenetic analysis of the sequence. We discuss the relevance of our results with respect to the evolution of the ChEs in general, in deuterostome invertebrates, and in chordates including vertebrates.