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 and Purpose—: ABC/2 is still widely accepted for volume estimations in spontaneous intracerebral hemorrhage (ICH) despite known limitations, which potentially accounts for controversial outcome-study results. The aim of this study was to establish and validate an automatic segmentation algorithm, allowing for quick and accurate quantification of ICH. Methods—: A segmentation algorithm implementing first- and second-order statistics, texture, and threshold features was trained on manual segmentations with a random-forest methodology. Quantitative data of the algorithm, manual segmentations, and ABC/2 were evaluated for agreement in a study sample (n=28) and validated in an independent sample not used for algorithm training (n=30). Results—: ABC/2 volumes were significantly larger compared with either manual or algorithm values, whereas no significant differences were found between the latter ( P <0.0001; Friedman+Dunn’s multiple comparison). Algorithm agreement with the manual reference was strong (concordance correlation coefficient 0.95 [lower 95% confidence interval 0.91]) and superior to ABC/2 (concordance correlation coefficient 0.77 [95% confidence interval 0.64]). Validation confirmed agreement in an independent sample (algorithm concordance correlation coefficient 0.99 [95% confidence interval 0.98], ABC/2 concordance correlation coefficient 0.82 [95% confidence interval 0.72]). The algorithm was closer to respective manual segmentations than ABC/2 in 52/58 cases (89.7%). Conclusions—: An automatic segmentation algorithm for volumetric analysis of spontaneous ICH was developed and validated in this study. Algorithm measurements showed strong agreement with manual segmentations, whereas ABC/2 exhibited its limitations, yielding inaccurate overestimations of ICH volume. The refined, yet time-efficient, quantification of ICH by the algorithm may facilitate evaluation of clot volume as an outcome predictor and trigger for surgical interventions in the clinical setting.

Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation.

Microglia are present throughout the central nervous system and are vital in neural repair, nutrition, phagocytosis, immunological regulation, and maintaining neuronal function. In a healthy spinal cord, microglia are accountable for immune surveillance, however, when a spinal cord injury occurs, the microenvironment drastically changes, leading to glial scars and failed axonal regeneration. In this context, microglia vary their gene and protein expression during activation, and proliferation in reaction to the injury, influencing injury responses both favorably and unfavorably. A dynamic and multifaceted injury response is mediated by microglia, which interact directly with neurons, astrocytes, oligodendrocytes, and neural stem/progenitor cells. Despite a clear understanding of their essential nature and origin, the mechanisms of action and new functions of microglia in spinal cord injury require extensive research. This review summarizes current studies on microglial genesis, physiological function, and pathological state, highlights their crucial roles in spinal cord injury, and proposes microglia as a therapeutic target.