The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

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” (t½) in order to describe the “fall” rate in serum Material 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 t½ of about 24 hours, even if very early sampling in these patients reveals rapid decreases (1-2 hours) though possibly of non-cerebral origin. In contrast, the t½ for NSE is comparably longer, ranging from 48-72 hours in severe TBI cases. The protein GFAP (n=18) appears to have t½ of about 24-48 hours in severe TBI. The protein UCH-L1 (n=9) present a t½ around 7 hours in mild TBI, and about 10 hours 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 >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.

BACKGROUND: Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets. OBJECTIVE: To describe the changes in intracranial monitoring variables over the past 25 yr. METHODS: Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017. RESULTS: CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%). CONCLUSION: We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.

Traumatic brain injury (TBI) and subarachnoid haemorrhage (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 neurological 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 (CSF) and the extracellular fluid (ECF), 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 imaging (PET), can provide a global in vivo measurement of inflammatory cell activity, which reveals a long-lasting process 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 auto-reactivity towards 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 indicates 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 multi-modal 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.

The aim of the study was to compare intracranial pressure (ICP)-derived cerebrovascular reactivity indices in their ability to predict six-month outcome, and to determine/compare critical thresholds related to outcome for each index in adult noncraniectomized traumatic brain injury (TBI). Using a retrospective cohort of nondecompressive craniectomy (non-DC) patients with TBI, we performed univariate and multi-variate binary logistic regression outcome analysis of: pressure reactivity index (PRx), pulse amplitude index (PAx), and a newly described index (RAC) calculated as the regression coefficient between ICP waveform amplitude and cerebral perfusion pressure (CPP). Finally, we performed sequential chi-square threshold analysis for each index as it related to six-month binary outcomes. Outcome was assessed via dichotomized Glasgow Outcome Scores (GOS): (A) favorable (GOS 4 or 5) versus unfavorable (GOS 3 or less), (B) alive versus dead. There were 358 non-DC patients with TBI included in all aspects of the analysis. In an analysis of the entire recording period for all patients using univariate binary logistic regression, the areas under the curves (AUCs) for favorable versus unfavorable outcome were: PRx (0.573, p < 0.0001), PAx (0.606, p < 0.0001), and RAC (0.655, p < 0.0001). Similarly, the AUCs for alive versus dead outcome were: PRx (0.651, p < 0.0001), PAx (0.705, p < 0.0001), and RAC (0.722, p < 0.0001). RAC displayed superior AUC statistics compared with PRx and PAx, using both univariate and multi-variate regression. RAC displayed more stable critical thresholds related to six-month outcomes. Thresholds for both favorable versus unfavorable and alive versus dead outcomes for PRx, PAx, and RAC across the entire recording period were: +0.35 and +0.35, 0 and +0.25, −0.10 and −0.05, respectively. In non-DC patients with TBI, RAC appears to be superior to PRx and PAx in six-month outcome prediction, using both univariate and multi-variate logistic regression. Further, RAC displayed more stable critical thresholds associated with binary outcomes at six months. Further analysis of RAC in TBI is required.