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Objective: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment., Methods: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome., Results: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs., Conclusion: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group., Protocol: The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582)., (© 2022. The Author(s).)

Introduction: Traumatic axonal injury (TAI) is a condition defined as multiple, scattered, small hemorrhagic, and/or non-hemorrhagic lesions, alongside brain swelling, in a more confined white matter distribution on imaging studies, together with impaired axoplasmic transport, axonal swelling, and disconnection after traumatic brain injury (TBI). Ever since its description in the 1980s and the grading system by Adams et al., our understanding of the processes behind this entity has increased., Methods: We performed a scoping systematic, narrative review by interrogating Ovid MEDLINE, Embase, and Google Scholar on the pathophysiology, biomarkers, and diagnostic tools of TAI patients until July 2020., Results: We underline the misuse of the Adams classification on MRI without proper validation studies, and highlight the hiatus in the scientific literature and areas needing more research. In the past, the theory behind the pathophysiology relied on the inertial force exerted on the brain matter after severe TBI inducing a primary axotomy. This theory has now been partially abandoned in favor of a more refined theory involving biochemical processes such as protein cleavage and DNA breakdown, ultimately leading to an inflammation cascade and cell apoptosis, a process now described as secondary axotomy., Conclusion: The difference in TAI definitions makes the comparison of studies that report outcomes, treatments, and prognostic factors a daunting task. An even more difficult task is isolating the outcomes of isolated TAI from the outcomes of severe TBI in general. Targeted bench-to-bedside studies are required in order to uncover further pathways involved in the pathophysiology of TAI and, ideally, new treatments.

Brain Trauma Foundation (BTF) Guidelines for medical management of severe traumatic brain injury (TBI) have become a global standard for the treatment of TBI patients. We aim to explore the evolution of the guidelines for the management of severe TBI. We reviewed the four editions of the BTF guidelines published over the past 20 years. The 1996 and 2000 editions were merged because of minimal differences, and are referred to as the 1996 edition. We described changes in topics and recommendations over time, and analyzed predictors of survival of recommendations with logistical regression. The guidelines contained 27 recommendations on 18 topics in 2016, 35 recommendations on 15 topics in 2007, and 22 recommendations on 10 topics in 1996. Substantial delays were found between the search for evidence and the guideline publication, ranging from 18 to 34 months. The overall body of evidence comprised 189 studies on 18 topics in 2016, compared with 156 studies on 15 topics in 2007 and 180 studies on 10 topics in 1996. Over time, a total of 175 studies were discarded from the evidence base following more rigorous grading of evidence. A total of 15/23 (65%) of the 1996/2000 recommendations were discarded over time. Out of 12 new recommendations introduced in the 2007 edition, 8 (66%) were discarded in 2016. Survival of recommendations varied between 33% and 100% for level I recommendations and between 11% and 31% for level II and III recommendations. No predictors of survival of recommendations were found. Substantial delays exist between literature search and publication, and survival rate of TBI guideline recommendations is poor. These factors may adversely affect currency and adherence to guidelines. The TBI community should take responsibility for improving the quality of the evidence base and ensuring that the translation of the evidence into guidelines supports clinicians in daily clinical practice.

Objective: Guidelines may reduce practice variation and optimize patient care. We aimed to study differences in guideline use in the management of traumatic brain injury (TBI) patients and analyze reasons for guideline non-adherence., Methods: As part of a prospective, observational, multicenter European cohort study, participants from 68 centers in 20 countries were asked to complete 72-item questionnaires regarding their management of severe TBI. Six questions with multiple sub-questions focused on guideline use and implementation., Results: Questionnaires were completed by 65 centers. Of these, 49 (75%) reported use of the Brain Trauma Foundation guidelines for the medical management of TBI or related institutional protocols, 11 (17%) used no guidelines, and 5 used other guidelines (8%). Of 54 centers reporting use of any guidelines, 41 (75%) relied on written guidelines. Four centers of the 54 (7%) reported no formal implementation efforts. Structural attention to the guidelines during daily clinical rounds was reported by 21 centers (38%). The most often reported reasons for non-adherence were "every patient is unique" and the presence of extracranial injuries, both for centers that did and did not report the use of guidelines., Conclusions: There is substantial variability in the use and implementation of guidelines in neurotrauma centers in Europe. Further research is needed to strengthen the evidence underlying guidelines and to overcome implementation barriers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Intracranial pressure (ICP) monitoring is one of the mainstays in the treatment of severe traumatic brain injury (TBI), but different approaches to monitoring exist. The aim of this systematic review and meta-analysis is to compare the effectiveness and complication rate of ventricular drainage (VD) versus intracranial parenchymal (IP) catheters to monitor and treat raised ICP in patients with TBI. Pubmed, Embase, Web of Science, Google Scholar, and the Cochrane Database were searched for articles comparing ICP monitoring-based management with VDs and monitoring with IP monitors through March 2018. Study selection, data extraction, and quality assessment were performed independently by two authors. Outcomes assessed were mortality, functional outcome, need for decompressive craniectomy, length of stay, overall complications, such as infections, and hemorrhage. Pooled effect estimates were calculated with random effects models and expressed as relative risk (RR) for dichotomous outcomes and mean difference (MD) for ordinal outcomes, with corresponding 95% confidence intervals (CI). Six studies were included: one randomized controlled trial and five observational cohort studies. Three studies reported mortality, functional outcome, and the need for a surgical decompression, and three only reported complications. The quality of the studies was rated as poor, with critical or serious risk of bias. The pooled analysis did not show a statistically significant difference in mortality (RR = 0.90, 95% CI = 0.60-1.36, p = 0.41) or functional outcome (MD = 0.23, 95% CI = 0.67-1.13, p = 0.61). The complication rate of VDs was higher (RR = 2.56, 95% CI = 1.17-5.61, p = 0.02), and consisted mainly of infectious complications; that is, meningitis. VDs caused more complications, particularly more infections, but there was no difference in mortality or functional outcome between the two monitoring modalities. However, the studies had a high risk of bias. A need exists for high quality comparisons of VDs versus IP monitor-based management strategies on patient outcomes.

Within a prospective, observational, multi-center cohort study 68 hospitals (of which 66 responded), mostly academic (n = 60, 91%) level I trauma centers (n = 44, 67%) in 20 countries were asked to complete questionnaires regarding the "standard of care" for severe neurotrauma patients in their hospitals. From the questionnaire pertaining to ICU management, 12 questions related to admission criteria were selected for this analysis. The questionnaires were completed by 66 centers. The median number of TBI patients admitted to the ICU was 92 [interquartile range (IQR): 52-160] annually. Admission policy varied; in 45 (68%) centers, patients with a Glasgow Come Score (GCS) between 13 and 15 without CT abnormalities but with other risk factors would be admitted to the ICU while the rest indicated that they would not admit these patients routinely to the ICU. We found no association between ICU admission policy and the presence of a dedicated neuro ICU, the discipline in charge of rounds, the presence of step down beds or geographic location (North- Western Europe vs. South - Eastern Europe and Israel). Variation in admission policy, primarily of mild TBI patients to ICU exists, even among high-volume academic centers and seems to be largely independent of other center characteristics. The observed variation suggests a role for comparative effectiveness research to investigate the potential benefit and cost-effectiveness of a liberal versus more restrictive admission policies., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate cognitive function 10 years after moderate-severe traumatic brain injury (TBI) and to investigate the associations among cognitive function, depression, and health-related quality of life (HRQoL). In this prospective cohort study, with measurements at 3, 6, 12, 18, 24, 36, and 120 months post-TBI, patients 18-67 years of age (n = 113) with moderate-severe TBI were recruited. Main outcome measures were depression (Center for Epidemiologic Studies-Depression Scale [CES-D]), subjective cognitive functioning (Cognitive Failure Questionnaire [CFQ]), objective cognitive functioning, and HRQoL (Medical Outcomes Study 36-Item Short Form Health Survey [SF-36]). Fifty of the initial 113 patients completed the 10 year follow-up. Twenty percent showed symptoms of depression (CES-D ≥ 16). These patients had more psychiatric symptoms at hospital discharge (p = 0.048) and were more often referred to rehabilitation or nursing homes (p = 0.015) than non-depressed patients. Further, they also had significantly lower scores in six of the eight subdomains of the SF-36. The non-depressed patients had equivalent scores to those of the Dutch norm-population on all subdomains of the SF-36. Cognitive problems at hospital discharge were related with worse cognitive outcome 10 years post-TBI, but not with depression or HRQoL. Ten years after moderate-severe TBI, only weak associations (p < 0.05) between depression scores and two objective cognitive functioning scores were found. However, there were moderate associations (p < 0.01) among depression scores, HRQoL, and subjective cognitive functioning. Therefore, signaling and treatment of depressive symptoms after moderate-severe TBI may be of major importance for optimizing HRQoL in the long term. We did not find strong evidence for associations between depression and objective cognitive functioning in the long term post-TBI. Disease awareness and selective dropping out may play a role in long-term follow-up studies in moderate-severe TBI. More long-term research is needed in this field.

Background: General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers., Methods: We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment., Results: The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO 2 ) was 36-40 mmHg (4.8-5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO 2 target of 30-35 mmHg (4-4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%)., Conclusions: Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome.

The objective of this prospective cohort study was to evaluate the probability of employment and predictors of employment in patients with moderate- to- severe traumatic brain injury (TBI) over 10-year follow-up. One hundred nine patients (18-67 years) were included with follow-up measurements 3, 6, 12, 18, 24, and 36 months and 10 years post-TBI. Potential predictors of employment probability included patient characteristics, injury severity factors, functional outcome measured at discharge from the hospital with the Glasgow Outcome Scale (GOS), Barthel Index (BI), Functional Independence Measure (FIM), and the Functional Assessment Measure (FAM). Forty-eight patients (42%) completed the 10-year follow-up. Three months post-TBI, 12% were employed, which gradually, but significantly, increased to 57% after 2-years follow-up (p < 0.001), followed by a significant decrease to 43% (p = 0.041) after 10 years. Ten years post-TBI, we found that employed persons had less-severe TBI, shorter length of hospital stay (LOS), and higher scores on the GOS, BI, FIM, and FAM at hospital discharge than unemployed persons. No significant differences in age, sex, educational level, living with partner/family or not, pre-injury employment, professional category, psychiatric symptoms, or discharge destination were found. Longitudinal multivariable analysis showed that time, pre-injury employment, FAM, and LOS were independent predictors of employment probability. We concluded that employment probability 10 years after moderate or severe TBI is related to injury severity and pre-injury employment. Future studies on vocational rehabilitation should focus on modifiable factors and take into consideration the effects of national legislation and national labor market forces.

Background: Patients with mild traumatic brain injury (TBI) who use anticoagulants prior to injury have an increased risk of intracranial complications. Sometimes these complications are delayed, even if the initial CT scan of the head is normal., Case Description: An 84-year-old woman who was using acenocoumarol presented elsewhere with mild TBI. She had no focal neurological deficit. The initial CT scan revealed no abnormalities and the patient was discharged home. That evening she had diffuse headache. The next day she was found with a reduced level of consciousness and was brought to our hospital. Her INR was 9.0 and a new CT scan showed an acute, left-sided subdural haematoma with a large mass effect., Conclusion: Serious delayed intracranial complications in patients with mild TBI who use anticoagulants are rare. In these patients INR measurement and a CT scan of the head are always indicated. Admission for observation may be considered. On discharge it is necessary to give clear instructions about warning symptoms.