Pieter E. Vos

Mild Traumatic Brain Injury

Traumatic brain injury (TBI) is one among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100–300/100 000. Intracranial complications of mild traumatic brain injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life threatening (case fatality rate 0.1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life‐threatening complication in a large number of individual patients. The 2002 EFNS guideline used the best evidence approach based on the literature until 2001 to guide initial management with respect to indications for computed tomography (CT), hospital admission, observation and follow‐up of MTBI patients. This updated EFNS guideline for initial management in MTBI proposes a more selective strategy for CT when major [dangerous mechanism, Glasgow Coma Scale (GCS) < 15, 2 points deterioration on the GCS, clinical signs of (basal) skull fracture, vomiting, anticoagulation therapy, post‐traumatic seizure] or minor (age, loss of consciousness, persistent anterograde amnesia, focal deficit, skull contusion, deterioration on the GCS) risk factors are present based on published decision rules with a high level of evidence. In addition, clinical decision rules for CT now exist for children as well. Since 2001, recommendations, although with a lower level of evidence, have been published for clinical observation in hospitals to prevent and treat other potential threats to the patient including behavioural disturbances (amnesia, confusion and agitation) and infection.

EFNS guideline on mild traumatic brain injury: report of an EFNS task force.

In 1999, a Task Force on Mild Traumatic Brain Injury (MTBI) was set up under the auspices of the European Federation of Neurological Societies. Its aim was to propose an acceptable uniform nomenclature for MTBI and definition of MTBI, and to develop a set of rules to guide initial management with respect to ancillary investigations, hospital admission, observation and follow‐up.

GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.

Background: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 μg/L for GFAP and 1.13 μg/L for S100B from a previous study. Methods: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. Results: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. Conclusion: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury

•  Introduction •  Classifying TBI ‐  Clinical injury severity ‐  Focal injury or diffuse injury •  Clinical characteristics ‐  Coma, confusion and subacute impairments ‐  Imaging TBI ‐  Focal and diffuse TBI: separate entities? •  Pathophysiological mechanisms of focal injury ‐  The essentials: glutamate and Ca2+ •  Pathophysiological mechanisms of diffuse injury ‐  A heterogeneous cascade of changes ‐  After axonal disconnection •  Conclusions

Epidemiology, severity classification and outcome of moderate and severe traumatic brain injury: A prospective multicenter study

Changes in the demographics, approach, and treatment of traumatic brain injury (TBI) patients require regular evaluation of epidemiological profiles, injury severity classification, and outcomes. This prospective multicenter study provides detailed information on TBI-related variables of 508 moderate-to-severe TBI patients. Variability in epidemiology and outcome is examined by comparing our cohort with previous multicenter studies. Additionally, the relation between outcome and injury severity classification assessed at different time points is studied. Based on the emergency department Glasgow Coma Scale (GCS), 339 patients were classified as having severe and 129 as having moderate TBI. In 15%, the diagnosis differed when the accident scene GCS was used for classification. In-hospital mortality was higher if severe TBI was diagnosed at both time points (44%) compared to moderate TBI at one or both time points (7-15%, p<0.001). Furthermore, 14% changed diagnosis when a threshold (≥6 h) for impaired consciousness was used as a criterion for severe TBI: In-hospital mortality was<5% when impaired consciousness lasted for<6 h. This suggests that combining multiple clinical assessments and using a threshold for impaired consciousness may improve the classification of injury severity and prediction of outcome. Compared to earlier multicenter studies, our cohort demonstrates a different case mix that includes a higher age (mean=47.3 years), more diffuse (Traumatic Coma Databank [TCDB] I-II) injuries (58%), and more major extracranial injuries (40%), with relatively high 6 month mortality rates for both severe (46%) and moderate (21%) TBI. Our results confirm that TBI epidemiology and injury patterns have changed in recent years whereas case fatality rates remain high.

Early prediction of favourable recovery 6 months after mild traumatic brain injury.

Background: Predicting outcome after mild traumatic brain injury (MTBI) is notoriously difficult. Although it is recognised that milder head injuries do not necessarily mean better outcomes, less is known about the factors that do enable early identification of patients who are likely to recover well. Objective: To develop and internally validate two prediction rules for identifying patients who have the highest chance for good 6 month recovery. Methods: A prospective cohort study was conducted among patients with MTBI admitted to the emergency department. Apart from MTBI severity indices, a range of pre-, peri- and early post-injury variables were considered as potential predictors, including emotional and physical functioning. Logistic regression modelling was used to predict the absence of postconcussional symptoms (PCS) and full return to work (RTW). Results: At follow-up, 64% of the 201 participating patients reported full recovery. Based on our prediction rules, patients without premorbid physical problems, low levels of PCS and post-traumatic stress early after injury had a 90% chance of remaining free of PCS. Patients with over 11 years of education, without nausea or vomiting on admission, with no additional extracranial injuries and only low levels of pain early after injury had a 90% chance of full RTW. The discriminative ability of the prediction models was satisfactory, with an area under the curve >0.70 after correction for optimism. Conclusions: Early identification of patients with MTBI who are likely to have good 6 month recovery was feasible on the basis of relatively simple prognostic models. A score chart was derived from the models to facilitate clinical application.

Outcome prediction in mild traumatic brain injury: age and clinical variables are stronger predictors than CT abnormalities

Mild traumatic brain injury (mTBI) is a common heterogeneous neurological disorder with a wide range of possible clinical outcomes. Accurate prediction of outcome is desirable for optimal treatment. This study aimed both to identify the demographic, clinical, and computed tomographic (CT) characteristics associated with unfavorable outcome at 6 months after mTBI, and to design a prediction model for application in daily practice. All consecutive mTBI patients (Glasgow Coma Scale [GCS] score: 13-15) admitted to our hospital who were age 16 or older were included during an 8-year period as part of the prospective Radboud University Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma using the Glasgow Outcome Scale-Extended (GOSE), dichotomized into unfavorable (GOSE score 1-6) and favorable (GOSE score 7-8) outcome groups. The predictive value of several variables was determined using multivariate binary logistic regression analysis. We included 2784 mTBI patients and found CT abnormalities in 20.7% of the 1999 patients that underwent a head CT. Age, extracranial injuries, and day-of-injury alcohol intoxication proved to be the strongest outcome predictors. The presence of facial fractures and the number of hemorrhagic contusions emerged as CT predictors. Furthermore, we showed that the predictive value of a scheme based on a modified Injury Severity Score (ISS), alcohol intoxication, and age equalled the value of one that also included CT characteristics. In fact, it exceeded one that was based on CT characteristics alone. We conclude that, although valuable for the identification of the individual mTBI patient at risk for deterioration and eventual neurosurgical intervention, CT characteristics are imperfect predictors of outcome after mTBI.

Recovery from mild traumatic brain injury: a focus on fatigue.

BackgroundFatigue is one of the most frequently reported symptoms after Mild Traumatic Brain Injury (MTBI). To date, systematic and comparative studies on fatigue after MTBI are scarce, and knowledge on causal mechanisms is lacking.ObjectivesTo determine the severity of fatigue six months after MTBI and its relation to outcome. Furthermore, to test whether injury indices, such as Glasgow Coma Scale scores, are related to higher levels of fatigue.MethodsPostal questionnaires were sent to a consecutive group of patients with an MTBI and a minor-injury control group, aged 18–60, six months after injury. Fatigue severity was measured with the Checklist Individual Strength. Postconcussional symptoms and limitations in daily functioning were assessed using the Rivermead Post Concussion Questionnaire and the SF-36.ResultsA total of 299 out of 618 eligible (response rate 52%) MTBI patients and 287 out of 482 eligible (response rate 60%) minor-injury patients returned the questionnaire. Ninety-five MTBI patients (32%) and 35 control patients (12%) were severely fatigued. Severe fatigue was highly associated with the experience of other symptoms, limitations in physical and social functioning, and fatigue related problems like reduced activity. Of various trauma severity indices, nausea and headache experienced on the ED were significantly related to higher levels of fatigue at six months.ConclusionsIn conclusion, one third of a large sample of MTBI patients experiences severe fatigue six months after injury, and this experience is associated with limitations in daily functioning. Our finding that acute symptoms and mechanism of injury rather than injury severity indices appear to be related to higher levels of fatigue warrants further investigation.

Abnormal whole-brain functional networks in homogeneous acute mild traumatic brain injury

Objectives: To evaluate the whole-brain resting-state networks in a homogeneous group of patients with acute mild traumatic brain injury (MTBI) and to identify alterations in functional connectivity induced by MTBI. Methods: Thirty-five patients with acute MTBI and 35 healthy control subjects, matched in age, gender, handedness, and education, underwent resting-state fMRI, susceptibility weighted imaging, neuropsychological, and postconcussive symptom assessments. We ensured the homogeneity of the patient group by limiting the injury mechanism to fronto-occipital impacts. Alterations in functional connectivity were analyzed by using data-driven independent component analysis, which is not biased by a priori region selection. Results: We found a decrease in functional connectivity within the motor-striatal network in the MTBI group. At the same time, patients showed deficits in psychomotor speed as well as in speed of information processing. We propose that although disorders in motor function after MTBI are rarely reported, injury still has an effect on motor functioning, which in its turn may also explain the reduction in speed of information processing. Further, we found a cluster of increased functional connectivity in the right frontoparietal network in the MTBI group. We suggest that this abnormal increased connectivity might reflect increased awareness to external environment and explain excessive cognitive fatigue reported by patients with MTBI. It might also underlie the physical postconcussive symptoms, such as headache and increased sensitivity to noise/light. Conclusions: We proved that whole-brain functional connectivity is altered early (within 4 weeks) after MTBI, suggesting that changes in functional networks underlie the cognitive deficits and postconcussive complaints reported by patients with MTBI.

Minor Head Injury: CT-based Strategies for Management—A Cost-effectiveness Analysis

PURPOSE To compare the cost-effectiveness of using selective computed tomographic (CT) strategies with that of performing CT in all patients with minor head injury (MHI). MATERIALS AND METHODS The internal review board approved the study; written informed consent was obtained from all interviewed patients. Five strategies were evaluated, with CT performed in all patients with MHI; selectively according to the New Orleans criteria (NOC), Canadian CT head rule (CCHR), or CT in head injury patients (CHIP) rule; or in no patients. A decision tree was used to analyze short-term costs and effectiveness, and a Markov model was used to analyze long-term costs and effectiveness. n-Way and probabilistic sensitivity analyses and value-of-information (VOI) analysis were performed. Data from the multicenter CHIP Study involving 3181 patients with MHI were used. Outcome measures were first-year and lifetime costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS Study results showed that performing CT selectively according to the CCHR or the CHIP rule could lead to substantial U.S. cost savings (