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Contains fulltext : 235370.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. MATERIALS AND METHODS: Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD(z)). Through linear regression, we evaluated the relation between microbleed concentration and MD(z) in predefined structures. RESULTS: In the cerebral hemispheres, MD(z) at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5-69.3], P = .017; right: B = 26.3 [95% CI 5.7-47.0], P = .014). No such relation was demonstrated in the central brain. MD(z) in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8-75.2], P < .000). MD(z) in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9-47.5], P = .023). CONCLUSIONS: SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

Serum concentrations of free thiols (key components of the extracellular antioxidant machinery) reflect the overall redox status of the human body. The objective of this exploratory study was to determine the concentrations of serum free thiols in the acute phase after traumatic brain injury (TBI) and their association with long-term outcome. In this observational cohort study, patients with TBI of various severity were included from a biobank of prospectively enrolled TBI patients. Further eligibility criteria included an available blood sample and head computed tomography data, obtained within 24 h of injury, as well as a functional outcome assessment (Glasgow Outcome Scale Extended (GOSE)) at 6 months post-injury. Serum free thiol concentrations were markedly lower in patients with TBI (n = 77) compared to healthy controls (n = 55) (mean ± standard deviation; 210.3 ± 63.3 vs. 301.8 ± 23.9 μM, P P = 0.016), suggesting that patients with good recovery experience less oxidative stress in the acute phase after TBI or have better redox function. Acute TBI is accompanied by a markedly lower concentration of serum free thiols compared to healthy controls indicating that serum free thiols may be a novel biomarker of TBI. Future studies are warranted to validate our findings and explore the clinical applicability and prognostic capability of this candidate-biomarker.

Introduction In order to augment the certainty of the radiological interpretation of “possible microbleeds” after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. Methods Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. Results Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. Conclusions Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.

Rapid risk-stratification of patients with acute traumatic brain injury (TBI) would inform management decisions and prognostication. The objective of this serum biomarker study (Biomarkers of Injury and Outcome [BIO]-Progesterone for Traumatic Brain Injury, Experimental Clinical Treatment [ProTECT]) was to test the hypothesis that serum biomarkers of structural brain injury, measured at a single, very early time-point, add value beyond relevant clinical covariates when predicting unfavorable outcome 6 months after moderate-to-severe acute TBI. BIO-ProTECT utilized prospectively collected samples obtained from subjects with moderate-to-severe TBI enrolled in the ProTECT III clinical trial of progesterone. Serum samples were obtained within 4 h after injury. Glial fibrillary acidic protein (GFAP), S100B, αII-spectrin breakdown product of molecular weight 150 (SBDP150), and ubiquitin C-terminal hydrolase-L1 (UCH-L1) were measured. The association between log-transformed biomarker levels and poor outcome, defined by a Glasgow Outcome Scale-Extended (GOS-E) score of 1–4 at 6 months post-injury, were estimated via logistic regression. Prognostic models and a biomarker risk score were developed using bootstrapping techniques. Of 882 ProTECT III subjects, samples were available for 566. Each biomarker was associated with 6-month GOS-E (p

Contains fulltext : 219917.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 203532.pdf (Publisher’s version ) (Closed access) In this study we investigated the effects of seeking versus avoiding proximity to mother on children's emotional recovery from a stressor. Sixty children 9-12 years underwent a moodinduction procedure and were randomly assigned to seek proximity from or avoid an image of their mothers. The effect of this manipulation on children's self-reported negative emotions, skin conductance and heart rate variability (respiratory sinus arhythmia) was assessed. Higher levels of attachment anxiety were linked to more self-reported sadness when children had to avoid mother, but no evidence for such an effect was found on a physiological level. For avoidant attachment, a similar pattern of results emerged, but both for self-reported sadness and skin conductance. 19 p.

Background The vegetative state, also known as the unresponsive wakefulness syndrome, is one of the worst possible outcomes of acquired brain injury and confronts rehabilitation specialists with various challenges. Emergence to (minimal) consciousness is classically considered unlikely beyond 3–6 months after non-traumatic or 12 months after traumatic etiologies. A growing body of evidence suggests that these timeframes are too narrow, but evidence regarding chances of recovery is still limited. Objective To identify the moment of recovery of consciousness in documented cases of late emergence from a vegetative state. Methods Four cases of apparent late recovery of consciousness, identified within a prospective cohort study, were studied in-depth by analyzing medical, paramedical and nursing files and interviewing the patients’ families about their account of the process of recovery. Results All patients were found to have shown signs of consciousness well within the expected time frame (5 weeks–2 months post-ictus). These behaviors, however, went unnoticed or were misinterpreted, leading to a diagnostic delay of several months to over 5 years. Absence of appropriate diagnostics, the use of erroneous terminology, sedative medication but also patient-related factors such as hydrocephalus, language barriers and performance fluctuations are hypothesized to have contributed to the delay. Conclusions Delayed recognition of signs of consciousness in patients in a vegetative state may not only lead to suboptimal clinical care, but also to distorted prognostic figures. Discriminating late recovery from the delayed discovery of consciousness, therefore, is vital to both clinical practice and science.

Maryse C Cnossen,1 Thomas A van Essen,2,3 Iris E Ceyisakar,1 Suzanne Polinder,1 Teuntje M Andriessen,4 Joukje van der Naalt,5 Iain Haitsma,6 Janneke Horn,7 Gaby Franschman,8 Pieter E Vos,9 Wilco C Peul,2,3 David K Menon,10 Andrew IR Maas,11 Ewout W Steyerberg,1,12 Hester F Lingsma1 1Center for Medical Decision Making, Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 2Neurosurgical Cooperative Holland, Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands; 4Department of Psychology, RIVAS Healthcare Group, Gorinchem, the Netherlands; 5Department of Neurology, University Medical Center Groningen, Groningen, the Netherlands; 6Department of Neurosurgery, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands; 7Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Department of Anesthesiology, VU University Medical Center Amsterdam, Amsterdam, the Netherlands; 9Department of Neurology, Slingeland Hospital, Doetinchem, the Netherlands; 10Division of Anaesthesia, University of Cambridge/Addenbrooke’s Hospital, Cambridge, UK; 11Department of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium; 12Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands Introduction: Observational studies of interventions are at risk for confounding by indication. The objective of the current study was to define the circumstances for the validity of methods to adjust for confounding by indication in observational studies. Patients and methods: We performed post hoc analyses of data prospectively collected from three European and North American traumatic brain injury studies including 1,725 patients. The effects of three interventions (intracranial pressure [ICP] monitoring, intracranial operation and primary referral) were estimated in a proportional odds regression model with the Glasgow Outcome Scale as ordinal outcome variable. Three analytical methods were compared: classical covariate adjustment, propensity score matching and instrumental variable (IV) analysis in which the percentage exposed to an intervention in each hospital was added as an independent variable, together with a random intercept for each hospital. In addition, a simulation study was performed in which the effect of a hypothetical beneficial intervention (OR 1.65) was simulated for scenarios with and without unmeasured confounders. Results: For all three interventions, covariate adjustment and propensity score matching resulted in negative estimates of the treatment effect (OR ranging from 0.80 to 0.92), whereas the IV approach indicated that both ICP monitoring and intracranial operation might be beneficial (OR per 10% change 1.17, 95% CI 1.01–1.42 and 1.42, 95% CI 0.95–1.97). In our simulation study, we found that covariate adjustment and propensity score matching resulted in an invalid estimate of the treatment effect in case of unmeasured confounders (OR ranging from 0.90 to 1.03). The IV approach provided an estimate in the similar direction as the simulated effect (OR per 10% change 1.04–1.05) but was statistically inefficient. Conclusion: The effect estimation of interventions in observational studies strongly depends on the analytical method used. When unobserved confounding and practice variation are expected in observational multicenter studies, IV analysis should be considered. Keywords: confounding, observational studies, traumatic brain injury, instrumental variable analysis, comparative effectiveness research

OBJECTIVES: Various definitions for concussion have been proposed, each having its strengths and weaknesses. We reviewed and compared current definitions and identified criteria necessary for an operational definition of sports-related concussion (SRC) in preparation of the 5th Concussion Consensus Conference (Berlin, Germany). We also assessed the role of biomechanical studies in informing an operational definition of SRC.DESIGN: This is a systematic literature review.DATA SOURCES: Data sources include MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Clinical Trials and SPORT Discus (accessed 14 September 2016).ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligibility criteria were studies reporting (clinical) criteria for diagnosing SRC and studies containing SRC impact data.RESULTS: Out of 1601 articles screened, 36 studies were included (2.2%), 14 reported on criteria for SRC definitions and 22 on biomechanical aspects of concussions. Six different operational definitions focusing on clinical findings and their dynamics were identified. Biomechanical studies were obtained almost exclusively on American football players. Angular and linear head accelerations linked to clinically confirmed concussions demonstrated considerable individual variation.SUMMARY/CONCLUSIONS: SRC is a traumatic brain injury that is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces with several common features that help define its nature. Limitations identified include that the current criteria for diagnosing SRC are clinically oriented and that there is no gold/standard to assess their diagnostic properties. A future, more valid definition of SRC would better identify concussed players by demonstrating high predictive positive/negative values. Currently, the use of helmet-based systems to study the biomechanics of SRC is limited to few collision sports. New approaches need to be developed to provide objective markers for SRC.

Background There is growing interest in health related quality of life (HRQoL) as an outcome measure in international trials. However, there might be differences in the conceptualization of HRQoL across different socio-cultural groups. The objectives of current study were: (I) to compare HRQoL, measured with the short form (SF)-36 of Dutch and Chinese traumatic brain injury (TBI) patients 1 year after injury and; (II) to assess whether differences in SF-36 profiles could be explained by cultural differences in HRQoL conceptualization. TBI patients are of particular interest because this is an important cause of diverse impairments and disabilities in functional, physical, emotional, cognitive, and social domains that may drastically reduce HRQoL. Methods A prospective cohort study on adult TBI patients in the Netherlands (RUBICS) and a retrospective cohort study in China were used to compare HRQoL 1 year post-injury. Differences on subscales were assessed with the Mann-Whitney U-test. The internal consistency, interscale correlations, item-internal consistency and item-discriminate validity of Dutch and Chinese SF-36 profiles were examined. Confirmatory factor analysis was performed to assess whether Dutch and Chinese data fitted the SF-36 two factor-model (physical and mental construct). Results Four hundred forty seven Dutch and 173 Chinese TBI patients were included. Dutch patients obtained significantly higher scores on role limitations due to emotional problems (p

The aim of this study was to explore modifications of functional connectivity in multiple resting-state networks (RSNs) after moderate to severe traumatic brain injury (TBI) and evaluate the relationship between functional connectivity patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied to identify RSNs. Between-subject analysis was performed using dual regression. Multiple linear regressions were used to investigate the relationship between abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe disability and low good recovery, respectively. TBI patients performed worse than HC on the domains attention and language. We found increased connectivity in sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on attention (p

BACKGROUND: Several prognostic models to predict outcome in traumatic brain injury (TBI) have been developed, but few are externally validated. We aimed to validate the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic models in a recent unselected patient cohort and to assess the additional prognostic value of extracranial injury. METHODS: The Prospective Observational COhort Neurotrauma (POCON) registry contains 508 patients with moderate or severe TBI, who were admitted in 2008 and 2009 to five trauma centers in the Netherlands. We predicted the probability of mortality and unfavorable outcome at 6 months after injury with the IMPACT prognostic models. We studied discrimination (area under the curve [AUC]) and calibration. We added the extracranial component of the Injury Severity Score (ISS) to the models and calculated the increase in AUC. RESULTS: The IMPACT models had an adequate discrimination in the POCON registry, with AUCs in the external validation between 0.85 and 0.90 for mortality and between 0.82 and 0.87 for unfavorable outcome. Observed outcomes agreed well with predicted outcomes. Adding extracranial injury slightly improved predictions in the overall population (unfavorable outcome: AUC increase of 0.002, p = 0.02; mortality: AUC increase of 0.000, p = 0.37) but more clearly in patients with moderate TBI (unfavorable outcome: AUC increase of 0.008, p G 0.01, mortality: AUC increase of 0.012, p = 0.02) and patients with minor computed tomographic result abnormalities (unfavorable outcome: AUC increase of 0.013, p G 0.01; mortality: AUC increase of 0.001, p =0 .08). CONCLUSION: The IMPACT models performed well in a recent series of TBI patients. We found some additional impact of extracranial injury on outcome, specifically in patients with less severe TBI or minor computed tomographic result abnormalities. ( JT rauma Acute Care Surg. 2013;74: 639Y646. Copyright * 2013 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Epidemiologic/prognostic study

This study tested whether children's more anxious and avoidant attachment is linked to decreased support-seeking behavior toward their mother during stress in middle childhood, and whether children's decreased support-seeking behavior enhances the impact of experiencing life events on the increase of depressive symptoms 18 months later. Ninety-eight 8- to 12-year-old children filled out questionnaires assessing their level of anxious and avoidant attachment and depressive symptoms. Children's support-seeking behavior was observed through measuring the time children waited before calling for their mother's help while carrying out a stressful task. Results supported the hypothesis that more anxiously or avoidantly attached children waited longer before seeking maternal support. Moreover, waiting longer was related to increased depressive symptoms at follow-up in children who reported more experienced life events. ispartof: Child Development vol:87 issue:1 pages:326-340 ispartof: location:United States status: published

Traumatic Brain Injury (TBI) is 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 large numbers of individual patients. The 2002 EFNS guidelines used a best evidence approach based on the literature until 2001 to guide initial management with respect to indications for CT, hospital admission, observation and follow up of MTBI patients. This updated EFNS guideline version for initial management inMTBI proposes a more selectively strategy for CT when major (dangerous mechanism, GCS

Contains fulltext : 109920.pdf (Publisher’s version ) (Closed access) Objective: This study compares inter-rater-reliability, lesion detection and clinical relevance of T2-weighted imaging (T2WI), Fluid Attenuated Inversion Recovery (FLAIR), T2*-gradient recalled echo (T2*-GRE) and Susceptibility Weighted Imaging (SWI) in Traumatic Brain Injury (TBI). Methods: Three raters retrospectively scored 56 TBI patients' MR images (12-76 years old, median TBI-MRI interval 7 weeks) on number, volume, location and intensity. Punctate lesions (diameter /=10 mm). Injury severity was assessed with the Glasgow Coma Scale (GCS), outcome with the Glasgow Outcome Scale-Extended (GOSE). Results: Inter-rater-reliability for lesion volume and punctate lesion count was good (ICC = 0.69-0.94) except for punctate lesion count on T2WI (ICC = 0.19) and FLAIR (ICC = 0.15). SWI showed the highest number of lesions (mean = 30.0), followed by T2*-GRE (mean = 15.4), FLAIR (mean = 3.1) and T2WI (mean = 2.2). Sequences did not differ in detected lesion volume. Punctate lesion count on T2*-GRE (r = -0.53) and SWI (r = -0.49) correlated with the GCS (p < 0.001). Conclusions: T2*-GRE and SWI are more sensitive than T2WI and FLAIR in detecting (haemorrhagic) traumatic punctate lesions. The correlation between number of punctate lesions on T2*-GRE/SWI and the GCS indicates that haemorrhagic lesions are clinically relevant. The considerable inter-rater-disagreement in this study advocates cautiousness in interpretation of punctate lesions using T2WI and FLAIR.

Contains fulltext : 107714.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch on prehospital run time and outcome in severe TBI. METHODS: Prehospital run times of 497 patients with severe TBI who were solely treated by a paramedic EMS (n=125) or an EMS/P-HEMS combination (n=372) were retrospectively analyzed. Other study parameters included the injury severity score (ISS), Glasgow Coma Scale (GCS), prehospital endotracheal intubation and predicted and observed outcome rates. RESULTS: Patients who received P-HEMS care were younger and had higher ISS values than solely EMS-treated patients (10%; P=0.04). The overall prehospital run time was 74+/-54min, with similar out-of-hospital times for EMS and P-HEMS treated patients. Prehospital endotracheal intubation was more frequently performed in the P-HEMS group (88%) than in the EMS group (35%; P

Item does not contain fulltext Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP ( approximately 2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 x 10(-8) ) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 x 10(-6) ) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. (c) 2012 Wiley Periodicals, Inc. 01 september 2012

Item does not contain fulltext 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/=6 h) for impaired consciousness was used as a criterion for severe TBI: In-hospital mortality was

Item does not contain fulltext BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of euro386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. RESULTS: The total cost of disorders of the brain was estimated at euro798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between euro285 for headache and euro30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was euro1550 on average but varied by country. The cost (in billion euroPPP 2010) of the disorders of the brain included in this study was as follows: addiction: euro65.7; anxiety disorders: euro74.4; brain tumor: euro5.2; child/adolescent disorders: euro21.3; dementia: euro105.2; eating disorders: euro0.8; epilepsy: euro13.8; headache: euro43.5; mental retardation: euro43.3; mood disorders: euro113.4; multiple sclerosis: euro14.6; neuromuscular disorders: euro7.7; Parkinson's disease: euro13.9; personality disorders: euro27.3; psychotic disorders: euro93.9; sleep disorders: euro35.4; somatoform disorder: euro21.2; stroke: euro64.1; traumatic brain injury: euro33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted euro477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives. 01 oktober 2011

Contains fulltext : 89903.pdf (Publisher’s version ) (Open Access) 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. 01 april 2010

Contains fulltext : 87730.pdf (Publisher’s version ) (Open Access) Computed tomography (CT) of the head has become the diagnostic tool of choice, particularly for moderate and severe traumatic brain injury (TBI). Various CT characteristics are associated with outcome, and may therefore be used as outcome predictors. One of the most prominent predictors appears to be the status of the basal cisterns. This study describes the prognostic value of the appearance of individual cisterns and ventricles in relation to that of the basal cisterns. Further, we determine the interrater and intrarater reliability in the evaluation of the cisterns and ventricles. All consecutive moderate and severe adult TBI patients admitted to our hospital were included in this study 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 (GOS-E). The predictive value of cisterns and ventricles was determined using multivariate binary logistic regression analysis. We included 126 moderate and 574 severe TBI patients. Absence (complete obliteration), but also compression of the ambient cisterns and/or the fourth ventricle were strongly related to unfavorable outcome and death and emerged as the only significant outcome predictors after multivariate analysis. The assessment of the ambient cisterns and the fourth ventricle had a satisfactory inter- and intrarater reliability (kappa coefficients: 0.80-0.95). We conclude that, because obliteration of the ambient cisterns and the fourth ventricle both are better than the status of the basal cisterns as outcome predictors, they might be used in CT prediction models in cases of moderate and severe TBI. 01 februari 2010

Contains fulltext : 88298.pdf (Publisher’s version ) (Open Access) Memory deficits are among the most frequently reported sequelae of mild traumatic brain injury (MTBI), especially early after injury. To date, these cognitive deficits remain poorly understood, as in most patients the brain is macroscopically intact. To identify the mechanism by which MTBI causes declarative memory impairments, we probed the functionality of the medial temporal lobe (MTL) and the prefrontal cortex (PFC), within 6 weeks after injury in 43 patients from a consecutive cohort, and matched healthy controls. In addition to neuropsychological measures of declarative memory and other cognitive domains, all subjects underwent functional magnetic resonance imaging (fMRI). Behavioral results showed poorer declarative memory performance in patients than controls, and decreasing performance with increasing duration of post-traumatic amnesia (a measure of injury severity). Task performance in the scanner was, as intended by the task and design, similar in patients and controls, and did not relate to injury severity. The task used reliably activated the MTL and PFC. Although we did not find significant differences in brain activity when comparing patients and controls, we revealed, in agreement with our neuropsychological findings, an inverse correlation between MTL activity and injury severity. In contrast, no difference in prefrontal activation was found between patients and controls, nor was there a relation with injury severity. On a behavioral level, injury severity was inversely related to declarative memory performance. In all, these findings suggest that reduced medial temporal functionality may contribute to poorer declarative memory performance in the post-acute stage of MTBI, especially in patients with longer post-traumatic amnesia. 01 september 2010

Contains fulltext : 88564.pdf (Publisher’s version ) (Closed access) 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 mug/L for GFAP and 1.13 mug/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS]

Item does not contain fulltext STUDY DESIGN: Literature review. OBJECTIVES: In traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and the prediction of recovery potential. An accurate prediction of the initial damage of the spinal cord that differentiates between the severities of SCI however, may help physicians in choosing a particular neuroprotective treatment in the acute phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim of this review was to describe (1) the current status of neurochemical biomarkers in SCI; (2) their potential diagnostic role in SCI. METHODS: MEDLINE was searched from 1966 to 2008 to identify publications concerning biomarkers in traumatic SCI. RESULTS: The biomarkers S-100beta, neuron-specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S-100beta have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI. CONCLUSIONS: Quantitative standards for determining the extent of SCI during the acute phase must be developed and validated. Even though increased concentrations of neurochemical biomarkers have been identified in patients with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.

Contains fulltext : 71531.pdf (Publisher’s version ) (Closed access) BACKGROUND AND PURPOSE: Functional outcome in patients with minor head injury with neurocranial traumatic findings on CT is largely unknown. We hypothesized that certain CT findings may be predictive of poor functional outcome. Materials and METHODS: All patients from the CT in Head Injury Patients (CHIP) study with neurocranial traumatic CT findings were included. The CHIP study is a prospective, multicenter study of consecutive patients, > or =16 years of age, presenting within 24 hours of blunt head injury, with a Glasgow Coma Scale (GCS) score of 13-14 or a GCS score of 15 and a risk factor. Primary outcome was functional outcome according to the Glasgow Outcome Scale (GOS). Other outcome measures were the modified Rankin Scale (mRS), the Barthel Index (BI), and number and severity of postconcussive symptoms. The association between CT findings and outcome was assessed by using univariable and multivariable regression analysis. RESULTS: GOS was assessed in 237/312 patients (76%) at an average of 15 months after injury. There was full recovery in 150 patients (63%), moderate disability in 70 (30%), severe disability in 7 (3.0%), and death in 10 (4.2%). Outcome according to the mRS and BI was also favorable in most patients, but 82% of patients had postconcussive symptoms. Evidence of parenchymal damage was the only independent predictor of poor functional outcome (odds ratio = 1.89, P = .022). CONCLUSION: Patients with neurocranial complications after minor head injury generally make a good functional recovery, but postconcussive symptoms may persist. Evidence of parenchymal damage on CT was predictive of poor functional outcome.

Contains fulltext : 51429.pdf (Publisher’s version ) (Closed access) PURPOSE: To prospectively and externally validate published national and international guidelines for the indications of computed tomography (CT) in patients with a minor head injury. MATERIALS AND METHODS: The study protocol was institutional review board approved. All patients implicitly consented to use of their deidentified data for research purposes. Between February 2002 and August 2004, data were collected in consecutive adult patients with blunt minor head injury (Glasgow Coma Scale score of 13-14 or 15) and a risk factor for neurocranial traumatic complications at presentation at four Dutch university hospitals. Primary outcome was any neurocranial traumatic CT finding. Secondary outcomes were clinically relevant traumatic CT findings and neurosurgical intervention. Sensitivity and specificity of each guideline for all outcomes and the number of patients needed to scan to detect one outcome (ie, the number of patients needed to undergo CT to find one patient with a neurocranial traumatic CT finding, a clinically relevant traumatic CT finding, or a CT finding that required neurosurgical intervention) were estimated. RESULTS: Data were available for 3181 patients. Only the European Federation of Neurological Societies guidelines reached a sensitivity of 100% for all outcomes. Specificity was 0.0%-0.5%. The Dutch guidelines had the lowest sensitivity (76.5%) for neurosurgical interventions. The best specificities for traumatic CT findings and neurosurgical interventions were reached with the criteria proposed by the United Kingdom National Institute for Clinical Excellence (NICE) (46.1% and 43.6%, respectively), albeit at relatively low sensitivities (82.1% and 94.1%, respectively). The number of patients needed to scan ranged from six to 13 for traumatic CT findings and from 79 to 193 for neurosurgical interventions. CONCLUSION: All validated guidelines demonstrated a trade-off between sensitivity and specificity. The lowest number of patients needed to scan for either of the outcomes was reached with the NICE criteria. Supplemental material: radiology.rsnajnls.org/cgi/content/full/2452061509/DC1 (c) RSNA, 2007.

Contains fulltext : 49838.pdf (Publisher’s version ) (Open Access) PURPOSE: To prospectively determine the accuracies of T2-weighted magnetic resonance (MR) imaging, dynamic contrast material-enhanced MR imaging, and quantitative three-dimensional (3D) proton MR spectroscopic imaging of the entire prostate for prostate cancer localization, with whole-mount histopathologic section findings as the reference standard. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all patients. Thirty-four consecutive men with a mean age of 60 years and a mean prostate-specific antigen level of 8 ng/mL were examined. The median biopsy Gleason score was 6. T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and 3D MR spectroscopic imaging were performed, and on the basis of the image data, two readers with different levels of experience recorded the location of the suspicious peripheral zone and central gland tumor nodules on each of 14 standardized regions of interest (ROIs) in the prostate. The degree of diagnostic confidence for each ROI was recorded on a five-point scale. Localization accuracy and ROI-based receiver operating characteristic (ROC) curves were calculated. RESULTS: For both readers, areas under the ROC curve for T2-weighted MR, dynamic contrast-enhanced MR, and 3D MR spectroscopic imaging were 0.68, 0.91, and 0.80, respectively. Reader accuracy in tumor localization with dynamic contrast-enhanced imaging was significantly better than that with quantitative spectroscopic imaging (P < .01). Reader accuracy in tumor localization with both dynamic contrast-enhanced imaging and spectroscopic imaging was significantly better than that with T2-weighted imaging (P < .01). CONCLUSION: Compared with use of T2-weighted MR imaging, use of dynamic contrast-enhanced MR imaging and 3D MR spectroscopic imaging facilitated significantly improved accuracy in prostate cancer localization.

Contains fulltext : 50465.pdf (Publisher’s version ) (Closed access) BACKGROUND: Fatigue 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. OBJECTIVES: To 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. METHODS: Postal 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. RESULTS: A 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. CONCLUSIONS: In 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.

The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement. This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps. A series of specific clinical questions were developed as part of the consensus process for the Berlin 2016 meeting. Each consensus question was the subject of a specific formal systematic review, which is published concurrently with this summary statement. Readers are directed to these background papers in conjunction with this summary statement as they provide the context for the issues and include the scope of published research, search strategy and citations reviewed for each question. This 2017 consensus statement also summarises each topic and recommendations in the context of all five CISG meetings (that is, 2001, 2004, 2008, 2012 as well as 2016). Approximately 60 000 published articles were screened by the expert panels for the Berlin …

The impact of disability following traumatic brain injury (TBI), assessed by functional measurement scales for TBI or by health-related quality of life (HRQoL), may vary because of a number of factors, including presence of depression or post-traumatic stress disorder (PTSD). The aim of this study was to assess prevalence and impact of depression and PTSD on functional outcome and HRQoL six and 12 months following mild TBI. We selected a sample of 1919 TBI patients who presented to the emergency department (ED) followed by either hospital admission or discharge to the home environment. The sample received postal questionnaires six and 12 months after treatment at the ED. The questionnaires included items regarding socio-demographics, the 36-item Short-Form Health Survey (SF-36), the Perceived Quality of Life Scale (PQoL), the Beck Depression Inventory, and the Impact of Event Scale. A total of 797 (42%) TBI patients completed the six-month follow-up survey. Depression and PTSD prevalence rates at both the six- and 12-month follow-up were 7% and 9%, respectively. Living alone was an independent predictor of depression and/or PTSD at six- and 12-month follow-up. Depression and PTSD were associated with a significantly decreased functional outcome (measured with Glasgow Outcome Scale Extended) and HRQoL (measured using the SF-36 and the PQoL). We conclude that depression and/or PTSD are relatively common in our sample of TBI patients and associated with a considerable decrease in functional outcome and HRQoL.

Traumatic brain injury (TBI) is one of the leading causes of injury-related death. In the United States alone, an estimated 1.7 million people sustain a TBI each year, and approximately 5.3 million people live with a TBI-related disability. The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $76.5 billion in the U.S. in the year 2000. Improving the limited treatment options for this condition remains challenging. However, recent reports from interdisciplinary working groups (consisting primarily of neurologists, neurosurgeons, neuropsychologists, and biostatisticians) have stated that to improve TBI treatment, important methodological lessons from the past must be taken into account in future clinical research. An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited understanding of the underlying biological concepts and methodological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy. Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors. Cerebrolysin has a favorable adverse effect profile, and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment. CAPTAIN is a randomized, double-blind, placebo-controlled, multi-center, multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales. The CAPTAIN trial will be the first TBI trial with a 'true' multidimensional approach based on full outcome scales, while avoiding prior weaknesses, such as loss of information through "dichotomization," or unrealistic assumptions such as "normal distribution."

Introduction: This study adds to the knowledge on somatization in adolescents by exploring its relationwith parenting behavior and the mediating/moderating role of physiological responses in adolescents to parenting behavior. Method: Eighteen adolescents with high and 18 adolescents with low somatization scores and their mothers completed a discussion task, from which observed parenting behavior scores were derived. Skin conductance in adolescents was measured before and during the discussion. Results: For adolescents with high levels of physiological responses, unadaptive parentingwas related to a higher chance of high somatization scores. For low physiologically responsive adolescents, the relation between parenting behavior and somatization was not significant. Conclusion: Parenting behavior is not univocally related to somatization in adolescents, but the association depends on physiological responses in adolescents. publisher: Elsevier articletitle: The association between parenting behavior and somatization in adolescents explained by physiological responses in adolescents journaltitle: International Journal of Psychophysiology articlelink: http://dx.doi.org/10.1016/j.ijpsycho.2014.05.008 content_type: article copyright: Copyright © 2014 Elsevier B.V. All rights reserved. ispartof: International Journal of Psychophysiology vol:93 issue:2 pages:261-266 ispartof: location:Netherlands status: published

Item does not contain fulltext PURPOSE: To analyze white matter pathologic abnormalities by using diffusion-tensor (DT) imaging in a multicenter prospective cohort of comatose patients following cardiac arrest or traumatic brain injury (TBI). MATERIALS AND METHODS: Institutional review board approval and informed consent from proxies and control subjects were obtained. DT imaging was performed 5-57 days after insult in 49 cardiac arrest and 40 TBI patients. To control for DT imaging-processing variability, patients' values were normalized to those of 111 control subjects. Automated segmentation software calculated normalized axial diffusivity (lambda1) and radial diffusivity (lambda perpendicular) in 19 predefined white matter regions of interest (ROIs). DT imaging variables were compared by using general linear modeling, and side-to-side Pearson correlation coefficients were calculated. P values were corrected for multiple testing (Bonferroni). RESULTS: In central white matter, lambda1 differed from that in control subjects in six of seven TBI ROIs and five of seven cardiac arrest ROIs (all P < .01). The lambda perpendicular differed from that in control subjects in all ROIs in both patient groups (P < .01). In hemispheres, lambda1 was decreased compared with that in control subjects in three of 12 TBI ROIs (P < .05) and nine of 12 cardiac arrest ROIs (P < .01). The lambda perpendicular was increased in all TBI ROIs (P < .01) and in seven of 12 cardiac arrest ROIs (P < .05). Cerebral hemisphere lambda1 was lower in cardiac arrest than in TBI in six of 12 ROIs (P < .01), while lambda perpendicular was higher in TBI than in cardiac arrest in eight of 12 ROIs (P < .01). Diffusivity values were symmetrically distributed in cardiac arrest (P < .001 for side-to-side correlation) but not in TBI patients. CONCLUSION: DT imaging findings are consistent with the known predominance of cerebral hemisphere axonal injury in cardiac arrest and chiefly central myelin injury in TBI. This consistency supports the validity of DT imaging for differentiating axon and myelin damage in vivo in humans. 01 februari 2014

Item does not contain fulltext One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed 'unresponsive wakefulness syndrome' (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous eye opening and breathing, but no signs of awareness of the self or the environment. We performed a systematic review of VS/UWS prevalence studies and assessed their reliability. Medline, Embase, the Cochrane Library, CINAHL and PsycINFO were searched in April 2013 for cross-sectional point or period prevalence studies explicitly stating the prevalence of VS/UWS due to acute causes within the general population. We additionally checked bibliographies and consulted experts in the field to obtain 'grey data' like government reports. Relevant publications underwent quality assessment and data-extraction. We retrieved 1032 papers out of which 14 met the inclusion criteria. Prevalence figures varied from 0.2 to 6.1 VS/UWS patients per 100 000 members of the population. However, the publications' methodological quality differed substantially, in particular with regards to inclusion criteria and diagnosis verification. The reliability of VS/UWS prevalence figures is poor. Methodological flaws in available prevalence studies, the fact that 5/14 of the studies predate the identification of the minimally conscious state (MCS) as a distinct entity in 2002, and insufficient verification of included cases may lead to both overestimation and underestimation of the actual number of patients in VS/UWS.

Item does not contain fulltext Study design:Prospective cohort study.Objectives:To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100beta, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS).Methods:A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades.Results:The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P

Contains fulltext : 181505.pdf (Publisher’s version ) (Closed access) An epidural hematoma of the clivus is reported in a 16-year-old boy after a motor vehicle accident. The diagnosis was made by magnetic resonance imaging. Only five similar cases have been reported in the literature. The patient was treated conservatively and recovered without neurological deficits. The mechanism of injury and formation of the hematoma in this region are discussed.

Contains fulltext : 118256.pdf (Publisher’s version ) (Open Access) ABSTRACT: BACKGROUND: Incomplete cervical cord syndrome without spinal instability is a very devastating event for the patient and the family. It is estimated that up to 25% of all traumatic spinal cord lesions belong to this category. The treatment for this type of spinal cord lesion is still subject of discussion. From a biological point of view early surgery could prevent secondary damage due to ongoing compression of the already damaged spinal cord. Historically, however, conservative treatment was propagated with good clinical results. Proponents for early surgery as well those favoring conservative treatment are still in debate. The proposed trial will contribute to the discussion and hopefully also to a decrease in the variability of clinical practice. METHODS/DESIGN: A randomized controlled trial is designed to compare the clinical outcome of early surgical strategy versus a conservative approach. The primary outcome is clinical outcome according to mJOA. This also measured by ASIA score, DASH score and SCIM III score. Other endpoints are duration of the stay at a high care department (medium care, intensive care), duration of the stay at the hospital, complication rate, mortality rate, sort of rehabilitation, and quality of life. A sample size of 36 patients per group was calculated to reach a power of 95%. The data will be analyzed as intention-to-treat at regular intervals, but the end evaluation will take place at two years post-injury. DISCUSSION: At the end of the study, clinical outcomes between treatments attitudes can be compared. Efficacy, but also efficiency can be determined. A goal of the study is to determine which treatment will result in the best quality of life for the patients. This study will certainly contribute to more uniformity of treatment offered to patients with a special sort of spinal cord injury. TRIAL REGISTRATION: Gov: NCT01367405.

Contains fulltext : 108749.pdf (Publisher’s version ) (Closed access) This prospective multicenter study investigated the association of the course of coagulation abnormalities with initial computed tomography (CT) characteristics and outcome in patients with isolated traumatic brain injury (TBI). Patient demographics, coagulation parameters, CT characteristics, and outcome data of moderate and severe TBI patients without major extracranial injuries were prospectively collected. Coagulopathy was defined as absent, early but temporary, delayed, or early and sustained. Delayed/sustained coagulopathy was associated with a higher incidence of disturbed pupillary responses (40% versus 27%; p

Introduction Authors of several studies have studied biomarkers and computed tomography (CT) findings in the acute phase after severe traumatic brain injury (TBI). However, the correlation between structural damage as assessed by neuroimaging and biomarkers has not been elucidated. The aim of this study was to investigate the relationships among neuronal (Ubiquitin carboxy-terminal hydrolase L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels in serum, neuroradiological findings and outcomes after severe TBI. Methods The study recruited patients from four neurotrauma centers. Serum samples for UCH-L1 and GFAP were obtained at the time of hospital admission and every 6 hours thereafter. CT scans of the brain were obtained within 24hrs of injury. Outcome was assessed by Glasgow Outcome Scale (GOS) at discharge and at 6 months. Results 81 severe TBI patients and 167 controls were enrolled. The mean serum levels of UCH-L1 and GFAP were higher (p < 0.001) in TBI patients compared to controls. UCH-L1 and GFAP serum levels correlated significantly with Glasgow Coma Scale (GCS) and CT findings. GFAP levels were higher in patients with mass lesions than in those with diffuse injury (2.95 ± 0.48 ng/ml versus 0.74 ± 0.11 ng/ml) while UCH-L1 levels were higher in patients with diffuse injury (1.55 ± 0.18 ng/ml versus 1.21 ± 0.15 ng/ml, p = 0.0031 and 0.0103, respectively). A multivariate logistic regression showed that UCH-L1 was the only independent predictor of death at discharge [adjusted odds ratios 2.95; 95% confidence interval, 1.46-5.97], but both UCH-L1 and GFAP levels strongly predicted death 6 months post-injury. Conclusions Relationships between structural changes detected by neuroimaging and biomarkers indicate each biomarker may reflect a different injury pathway. These results suggest that protein biomarkers could provide better characterization of subjects at risk for specific types of cellular damage than that obtained with neuroimaging alone, as well as provide valuable information about injury severity and outcome after severe TBI.

Contains fulltext : 97753.pdf (Publisher’s version ) (Closed access) Intracranial lesion volume and midline shift are powerful outcome predictors in moderate and severe traumatic brain injury (TBI), and therefore they are used in TBI and computed tomography (CT) classification schemes, like the Traumatic Coma Data Bank (TCDB) classification. In this study we aimed to explore the prognostic value of lesion volume and midline shift in moderate and severe TBI as measured from acute cranial CT scans. Also, we wanted to determine interrater reliability for the evaluation of these CT abnormalities. We included all consecutive moderate and severe TBI patients admitted to our hospital who were aged >/=16 years, over an 8-year period, as part of the prospective Radboud University Brain Injury Cohort Study. Six months post-trauma we assessed outcomes using the Glasgow Outcome Scale-Extended (GOS-E). We analyzed 605 patients and found an association of both lesion volume and midline shift with outcome; increases were associated with a higher frequency of patients with an unfavorable outcome or death. A cut-off value, such as that used in the TCDB CT classification (lesion volume 25 mL and midline shift 5 mm), was not found. The average interrater difference in volume measurement was 6.8 mL, and it was 0.2 mm for the determination of degree of shift. Using lesion volume and midline shift as continuous variables in prognostic models might be preferable over the use of threshold values, although an association of these variables with outcome in relation to other CT abnormalities was not tested. The data provided here will be useful for stratification of patients enrolled in clinical trials of neuroprotective therapies.

Contains fulltext : 88949.pdf (Publisher’s version ) (Closed access) 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 ($120 million and $71 million, respectively), and the CCHR was the most cost-effective at reference-case analysis. When the prediction rule had lower than 97% sensitivity for the identification of patients who required neurosurgery, performing CT in all patients was cost-effective. The CHIP rule was most likely to be cost-effective. At VOI analysis, the expected value of perfect information was $7 billion, mainly because of uncertainty about long-term functional outcomes. Conclusion: Selecting patients with MHI for CT renders cost savings and may be cost-effective, provided the sensitivity for the identification of patients who require neurosurgery is extremely high. Uncertainty regarding long-term functional outcomes after MHI justifies the routine use of CT in all patients with these injuries. 01 februari 2010

Contains fulltext : 88861.pdf (Publisher’s version ) (Open Access) We describe a 76-year-old patient who suffered a brainstem TIA just before being anesthetised for cardiac surgery. The TIA was registered on BIS and resulted in a drop in BIS to a value of 60. When consciousness returned spontaneously, the BIS increased to 85. The relative use of the BIS during an operation is discussed. We believe that the lack of input from the brainstem to the frontal cortex resulted in the reduced cortical electrical activity as registered with the BIS.

Contains fulltext : 87476.pdf (Publisher’s version ) (Open Access) Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13-15) and moderate (GCS 9-12) to severe (GCS

Contains fulltext : 88826.x.pdf (Publisher’s version ) (Closed access) BACKGROUND: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. METHODS: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) < or = 8 on admission]. RESULTS: Seventy-six of 119 patients survived and were eligible for follow-up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3-68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92-83.33] and the development of spasticity (RR 16.94, CI 3.96-71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. CONCLUSIONS: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow-up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism. 01 september 2010

ContextA wide range (15–56%) of prevalences of anterior pituitary insufficiency are reported in patients after traumatic brain injury (TBI). However, different study populations, study designs, and diagnostic procedures were used. No data are available on emergency-department-based cohorts of TBI patients.ObjectiveTo assess the prevalence of pituitary dysfunction in an emergency-department-based cohort of TBI patients using strict endocrinological diagnostic criteria.MethodsOf all the patients presenting in the emergency department with TBI over a 2-year period, 516 matched the inclusion criteria. One hundred and seven patients (77 with mild TBI and 30 with moderate/severe TBI) agreed to participate. They were screened for anterior pituitary insufficiency by GHRH–arginine testing, evaluation of fasting morning hormone levels (cortisol, TSH, free thyroxine, FSH, LH, and 17β-estradiol or testosterone), and menstrual history 3–30 months after TBI. Abnormal screening results were defined as low peak GH to GHRH–arginine, or low levels of any of the end-organ hormones with low or normal pituitary hormone levels. Patients with abnormal screening results were extensively evaluated, including additional hormone provocation tests (insulin tolerance test, ACTH stimulation test, and repeated GHRH–arginine test) and assessment of free testosterone levels.ResultsScreening results were abnormal in 15 of 107 patients. In a subsequent extensive endocrine evaluation, anterior pituitary dysfunction was diagnosed in only one patient (partial hypocortisolism).ConclusionBy applying strict diagnostic criteria to an emergency-department-based cohort of TBI patients, it was shown that anterior pituitary dysfunction is rare (

Contains fulltext : 70471.pdf (Publisher’s version ) (Closed access) 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.

Contains fulltext : 52728.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To compare nonreferred, emergency department (ED)-admitted mild traumatic brain injury (MTBI) patients with and without self-reported cognitive complaints on (1) demographic variables and injury characteristics; (2) neuropsychological test performance; (3) 12-day self-monitoring of perceived cognitive problems; and (4) emotional distress, physical functioning, and personality. METHODS: (Neuro)psychological assessment was carried out 6 months post-injury in 79 patients out of a cohort of 618 consecutive MTBI patients aged 18-60, who attended the ED of our level I trauma centre. Cognitive complaints were assessed with the Rivermead Postconcussional Symptoms Questionnaire (RPSQ). In addition, patients monitored concentration problems and forgetfulness during 12 consecutive days. RESULTS: Self-reported cognitive complaints were reported by 39% of the patients. These complaints were strongly related to lower educational levels, emotional distress, personality, and poorer physical functioning (especially fatigue) but not to injury characteristics. Severity of self-reported cognitive complaints was neither associated with the patients' daily observations of cognitive problems nor with outcome on a range of neuropsychological tests. CONCLUSION: Self-reported cognitive complaints were more strongly related to premorbid traits and physical and emotional state factors than to actual cognitive impairments. In line with previous work, this suggests that treatment of emotional distress and fatigue may also reduce cognitive complaints. Cognitive outcome assessment of symptomatic MTBI patients should not be restricted to checklist ratings only, but also include a (neuro)psychological screening. In addition, daily monitoring of complaints is a useful method to gather information about the frequency and pattern of cognitive problems in daily life.