Consensus statement from the 2014 International Microdialysis Forum.

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. – Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); M.G.B. - Wellcome Trust Dept Health Healthcare Innovation Challenge Fund (HICF-0510-080); L. H. - The Swedish Research Council, VINNOVA and Uppsala Berzelii Technology Centre for Neurodiagnostics; S. M. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; D.K.M. - NIHR Senior Investigator Award to D.K.M., NIHR Cambridge Biomedical Research Centre (Neuroscience Theme), FP7 Program of the European Union; M. O. - Swiss National Science Foundation and the Novartis Foundation for Biomedical Research; J.S. - Fondo de Investigación Sanitaria (Instituto de Salud Carlos III) (PI11/00700) co-financed by the European Regional Development; M.S. – NIHR University College London Hospitals Biomedical Research Centre; N. S. - Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-

Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes-an analysis of CENTER-TBI data

Purpose: We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI). Methods: From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]. Results: Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001). Conclusion: Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.publishedVersio

Clinical and Imaging Characteristics, Care Pathways, and Outcomes of Traumatic Epidural Hematomas: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study

BACKGROUND AND OBJECTIVES: Guideline recommendations for surgical management of traumatic epidural hematomas (EDHs) do not directly address EDHs that co-occur with other intracranial hematomas; the relative rates of isolated vs nonisolated EDHs and guideline adherence are unknown. We describe characteristics of a contemporary cohort of patients with EDHs and identify factors influencing acute surgery. METHODS: This research was conducted within the longitudinal, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury cohort study which prospectively enrolled patients with traumatic brain injury from 65 hospitals in 18 European countries from 2014 to 2017. All patients with EDH on the first scan were included. We describe clinical, imaging, management, and outcome characteristics and assess associations between site and baseline characteristics and acute EDH surgery, using regression modeling. RESULTS: In 461 patients with EDH, median age was 41 years (IQR 24-56), 76% were male, and median EDH volume was 5 cm3 (IQR 2-20). Concomitant acute subdural hematomas (ASDHs) and/or intraparenchymal hemorrhages were present in 328/461 patients (71%). Acute surgery was performed in 99/461 patients (21%), including 70/86 with EDH volume ≥30 cm3 (81%). Larger EDH volumes (odds ratio [OR] 1.19 [95% CI 1.14-1.24] per cm3 below 30 cm3), smaller ASDH volumes (OR 0.93 [95% CI 0.88-0.97] per cm3), and midline shift (OR 6.63 [95% CI 1.99-22.15]) were associated with acute surgery; between-site variation was observed (median OR 2.08 [95% CI 1.01-3.48]). Six-month Glasgow Outcome Scale–Extended scores ≥5 occurred in 289/389 patients (74%); 41/389 (11%) died. CONCLUSION: Isolated EDHs are relatively infrequent, and two-thirds of patients harbor concomitant ASDHs and/or intraparenchymal hemorrhages. EDHs ≥30 cm3 are generally evacuated early, adhering to Brain Trauma Foundation guidelines. For heterogeneous intracranial pathology, surgical decision-making is related to clinical status and overall lesion burden. Further research should examine the optimal surgical management of EDH with concomitant lesions in traumatic brain injury, to inform updated guidelines.publishedVersio

Disparities in casemix, acute interventions, discharge destinations and mortality of patients with traumatic brain injury between Europe and India

Background Traumatic brain injury (TBI) is a major global health problem that disproportionally affects low- and middle-income countries. The needs for patients with TBI therefore may differ between levels of national development. We aimed to describe differences in epidemiology and acute care provision of TBI between India and Europe. Methods We used data from two prospective observational registry studies – the Collaborative Indian NeuroTrauma Effectiveness Research in TBI (CINTER-TBI) and the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI), which included TBI patients with an indication for brain CT-scan presenting to 65 centres across Europe and Israel and two trauma centres in India. We performed descriptive analyses of demographic, injury, and treatment characteristics and used random-effects logistic regression with covariate adjustment to examine the likelihood of acute neurosurgical interventions and in-hospital mortality. Results We included 22 849 patients from CENTER-TBI and 3904 from CINTER-TBI. The median age in Europe was 55 years (IQR = 32–76) compared to 27 years (IQR = 18–40) in India. The most common cause of TBI in Europe were falls (n = 12150 (53%), while traffic incidents predominated in India (n = 2130 (55%)). The proportion of patients with severe TBI was higher in India (n = 867 (22%)) than in Europe (n = 1661 (7%). Professional pre-hospital care involving ambulance service was utilised by three-fourths (n = 17203 (75%)) of European and less than a one-tenth (n = 224 (6%)) of Indian patients in our sample. Patients with severe TBI were more likely to undergo surgical contusion/haematoma evacuation in India compared to Europe (OR = 2.0; 95% CI = 1.7–2.5) and Indian patients had higher odds of undergoing intracranial pressure monitor placement (OR = 2.3; 95% CI = 2.0–2.7). A primary decompressive craniectomy was likewise more often performed in the Indian cohort (OR = 5.1; 95% CI = 3.5–7.5). Discharge destinations in Europe included rehabilitation centres (n = 1261 (6%)) or nursing homes (n = 1208 (5%)), which was rarely the case in India (n = 13 (0%) and n = 9 (0%), respectively). Conclusions Substantial disparities between India and Europe exist along the neurotrauma care chain, with both systems being likely to face unique features and challenges in the future.publishedVersio

Comparability of (Post-Concussion) Symptoms across Time in Individuals after Traumatic Brain Injury: Results from the CENTER-TBI Study

Post-concussion symptoms often occur after TBI, persist and cause disabilities. The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is widely used in this population, but little is known about the comparability of the symptoms over time, i.e., longitudinal measurement invariance (MI). The objectives of this study were to analyze the longitudinal MI of RPQ symptoms from three to twelve months after TBI and to find factors related to RPQ symptoms. The study involved 1023 individuals after TBI who took part in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study and completed the RPQ at three, six and twelve months post-injury. Longitudinal confirmatory factor analysis showed that the three-factor structure (somatic, emotional and cognitive) remains stable within one year after TBI. Linear mixed models revealed that sex, injury cause and prior psychiatric problems were related to the RPQ three-factor structure as well as to the RPQ total score. The study strengthens evidence for the RPQ’s factorial structure stability within one year after TBI and identifies sex, injury cause and prior psychiatric problems as important factors that may help clinicians to prevent future complications of symptomatology after TBI.publishedVersio

Early versus delayed cranioplasty after decompressive craniectomy in traumatic brain injury: a multicenter observational study within CENTER-TBI and Net-QuRe

OBJECTIVE The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). METHODS The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale–Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC. RESULTS Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61–1.21 and 0.88, 95% CI 0.48–1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2–16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7–4.7) and QOLIBRI scores (β −1.9, 95% CI −9.1 to 9.6) were similar between the two groups. CONCLUSIONS Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient’s chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus.publishedVersionThis paper is locked due to copyright restriction

Consensus statement from the 2014 International Microdialysis Forum

This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00134-015-3930-yMicrodialysis enables the chemistry of the extracellular interstitial space to be measured. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004 a consensus document on the clinical application of cerebral microdialysis was published. Since then there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.We gratefully acknowledge financial support for participants as follows: P.J.H. - National Institute for Health Research (NIHR) Professorship and the NIHR Biomedical Research Centre, Cambridge; I.J. ? Medical Research Council (G1002277 ID 98489); A. H. - Medical Research Council, Royal College of Surgeons of England; K.L.H.C. - NIHR Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); M.G.B. - Wellcome Trust Dept Health Healthcare Innovation Challenge Fund (HICF-0510-080); L. H. - The Swedish Research Council, VINNOVA and Uppsala Berzelii Technology Centre for Neurodiagnostics; S. M. - Fondazione IRCCS C? Granda Ospedale Maggiore Policlinico; D.K.M. - NIHR Senior Investigator Award to D.K.M., NIHR Cambridge Biomedical Research Centre (Neuroscience Theme), FP7 Program of the European Union; M. O. - Swiss National Science Foundation and the Novartis Foundation for Biomedical Research; J.S. - Fondo de Investigaci?n Sanitaria (Instituto de Salud Carlos III) (PI11/00700) co-financed by the European Regional Development; M.S. ? NIHR University College London Hospitals Biomedical Research Centre; N. S. - Fondazione IRCCS C? Granda Ospedale Maggiore Policlinico

Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe

Purpose: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. Methods: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. Results: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatme

Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study

Introduction The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI. Methods We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury. Results Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms. Conclusion The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.publishedVersio