Acute serum free thiols: a potentially modifiable biomarker of oxidative stress following traumatic brain injury.

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 < 0.001) indicating increased oxidative stress. Concentrations of serum free thiols were higher in patients with complete functional recovery (GOSE = 8) than in patients with incomplete recovery (GOSE < 8) (median [interquartile range]; 235.7 [205.1-271.9] vs. 205.2 [173-226.7] µM, 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.

The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study.

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.

Cerebrolysin after moderate to severe traumatic brain injury: prospective meta-analysis of the CAPTAIN trial series.

INTRODUCTION: This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. MATERIALS AND METHODS: The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. RESULTS: A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a "small-to-medium" sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. DISCUSSION: The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.

INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

Unexpected emergence from the vegetative state: delayed discovery rather than late recovery of consciousness.

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.

Association of Very Early Serum Levels of S100B, Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and Spectrin Breakdown Product with Outcome in ProTECT III.

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 < 0.001). Compared with a model containing baseline patient variables/characteristics, inclusion of S100B and GFAP significantly improved prognostic capacity (p ≤ 0.05 both comparisons); conversely, UCH-L1 and SBDP did not. A final predictive model incorporating baseline patient variables/characteristics and biomarker data (S100B and GFAP) had the best prognostic capability (area under the curve [AUC] = 0.85, 95% confidence interval [CI]: CI 0.81-0.89). Very early measurements of brain-specific biomarkers are independently associated with 6-month outcome after moderate-to-severe TBI and enhance outcome prediction.

The association between post-concussion symptoms and health-related quality of life in patients with mild traumatic brain injury.

A subset of mild traumatic brain injury (mTBI) patients experience post-concussion symptoms. When a cluster of post-concussion symptoms persists for over three months, it is referred to as post-concussion syndrome (PCS). Little is known about the association between PCS and Health-Related Quality of Life (HRQoL) after mTBI. The aims of this study were to assess the implications of PCS on HRQoL six months after mTBI and the relationship between PCS and HRQoL domains. A prospective observational cohort study was conducted among a sample of mTBI patients. Follow-up postal questionnaires at six months after emergency department (ED) admission included socio-demographic information, the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), and HRQoL measured with the 36-item Short-Form Health Survey (SF-36) and the Perceived Quality of Life Scale (PQoL). In total, 731 mTBI patients were included, of whom 38.7% were classified as suffering from PCS. Patients with PCS had significantly lower scores on all SF-36 domains, lower physical and mental component summary scores and lower mean PQoL scores compared to patients without PCS. All items of the RPQ were negatively correlated to all SF-36 domains and PQoL subscale scores, indicating that reporting problems on any of the RPQ symptoms was associated with a decrease on different aspects of an individuals' HRQoL. To conclude, PCS is common following mTBI and patients with PCS have a considerably lower HRQoL. A better understanding of the relationship between PCS and HRQoL and possible mediating factors in this relationship could improve intervention strategies, the recovery process for mTBI patients and benchmarking.

Adjusting for confounding by indication in observational studies: a case study in traumatic brain injury.

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.

Divergent Classification Methods of Post-Concussion Syndrome after Mild Traumatic Brain Injury: Prevalence Rates, Risk Factors, and Functional Outcome.

Mild traumatic brain injury (mTBI) is a common diagnosis and approximately one third of mTBI patients experience a variety of cognitive, emotional, psychosocial, and behavioral post-concussion symptoms. When a cluster of these symptoms persists for more than 3 months they are often classified as post-concussion syndrome (PCS). The objective of this study was to determine prevalence rates, risk factors, and functional outcome associated with PCS 6 months after mTBI, applying divergent classification methods. Follow-up questionnaires at 6 months after mTBI included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE). The RPQ was analyzed according to different classification methods: the mapped International Classification of Diseases, 10th revision (ICD-10)/Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the RPQ total score, the RPQ3 and the three-factor model using two different cutoff points (mild or worse and moderate or worse). Our results from a sample of 731 mTBI patients showed that prevalence rates of PCS ranged from 11.4% to 38.7% using divergent classification methods. According to all eight methods, 6.3% (n = 46) of mTBI patients experienced PCS. Applying the divergent classification methods resulted in a different set of predictors being statistically significantly associated with PCS, and a different percentage of overlap with functional impairment, measured with the GOSE. In conclusion, depending on the classification method and rating score used, prevalence rates of PCS deviated considerably. For future research, consensus regarding the diagnostic criteria for PCS and the analysis of the RPQ should be reached, to enhance comparability of studies regarding PCS after mTBI.

What is the definition of sports-related concussion: a systematic review.

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.

Comparing health-related quality of life of Dutch and Chinese patients with traumatic brain injury: do cultural differences play a role?

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 < .001) and general health (p < .001), while Chinese patients obtained significantly higher scores on physical functioning (p < .001) and bodily pain (p = .001). Scores on these subscales were not explained by cultural differences in conceptualization, since item- and scale statistics were all sufficient. However, differences among Dutch and Chinese patients were found in the conceptualization of the domains vitality, mental health and social functioning. CONCLUSIONS: One year after TBI, Dutch and Chinese patients reported a different pattern of HRQoL. Further, there might be cultural differences in the conceptualization of some of the SF-36 subscales, which has implications for outcome evaluation in multi-national trials.

Causes and Consequences of Treatment Variation in Moderate and Severe Traumatic Brain Injury: A Multicenter Study.

OBJECTIVES: Although guidelines have been developed to standardize care in traumatic brain injury, between-center variation in treatment approach has been frequently reported. We examined variation in treatment for traumatic brain injury by assessing factors influencing treatment and the association between treatment and patient outcome. DESIGN: Secondary analysis of prospectively collected data. SETTING: Five level I trauma centers in the Netherlands (2008-2009). PATIENTS: Five hundred three patients with moderate or severe traumatic brain injury (Glasgow Coma Scale, 3-13). INTERVENTIONS: We examined variation in seven treatment parameters: direct transfer, involvement of mobile medical team, mechanical ventilation, intracranial pressure monitoring, vasopressors, acute neurosurgical intervention, and extracranial operation. MEASUREMENTS AND MAIN RESULTS: Data were collected on patient characteristics, treatment, and 6-month Glasgow Outcome Scale-Extended. Multivariable logistic regression models were used to assess the extent to which treatment was determined by patient characteristics. To examine whether there were between-center differences in treatment, we used unadjusted and adjusted random effect models with the seven treatment parameters as dependent variables. The influence of treatment approach in a center (defined as aggressive and nonaggressive based on the frequency intracranial pressure monitoring) on outcome was assessed using multivariable random effect proportional odds regression models in those patients with an indication for intracranial pressure monitoring. Sensitivity analyses were performed to test alternative definitions of aggressiveness. Treatment was modestly related to patient characteristics (Nagelkerke R range, 0.12-0.52) and varied widely among centers, even after case-mix correction. Outcome was more favorable in patients treated in aggressive centers than those treated in nonaggressive centers (OR, 1.73; 95% CI, 1.05-3.15). Sensitivity analyses, however, illustrated that the aggressiveness-outcome association was dependent on the definition used. CONCLUSIONS: The considerable between-center variation in treatment for patients with brain injury can only partly be explained by differences in patient characteristics. An aggressive treatment approach may imply better outcome although further confirmation is required.

Effects of an Integrated 'Fast Track' Rehabilitation Service for Multi-Trauma Patients: A Non-Randomized Clinical Trial in the Netherlands.

OBJECTIVES: The effects on health related outcomes of a newly-developed rehabilitation program, called 'supported Fast Track multi-trauma rehabilitation service' (Fast Track), were evaluated in comparison with conventional trauma rehabilitation service (Care as Usual). METHODS: Prospective, multi-center, non-randomized controlled study. Between 2009 and 2012, 132 adult multi-trauma patients were included: 65 Fast Track and 67 Care as Usual patients with an Injury Severity Score ≥16, complex multiple injuries in several extremities or complex pelvic and/or acetabulum fractures. The Fast Track program involved: integrated coordination between trauma surgeon and rehabilitation physician, shorter stay in hospital with faster transfer to a specialized trauma rehabilitation unit, earlier start of multidisciplinary treatment and 'non-weight bearing' mobilization. Primary outcomes were functional status (FIM) and quality of life (SF-36) measured through questionnaires at baseline, 3, 6, 9 and 12 months post-trauma. Outcomes were analyzed using a linear mixed-effects regression model. RESULTS: The FIM scores significantly increased between 0 and 3 months (p<0.001) for both groups showing that they had improved overall, and continued to improve between 3 and 6 months for Fast Track (p = 0.04) and between 3 and 9 months for Care as Usual (p = 0.03). SF-36 scores significantly improved in both groups between 3 and 6 months (Fast Track, p<0.001; Care as Usual, p = 0.01). At 12 months, SF-36 scores were still below (self-reported) baseline measurements of patient health prior to the accident. However, the FIM and SF-36 scores differed little between the groups at any of the measured time points. CONCLUSION: Both Fast Track and Care as Usual rehabilitation programs were effective in that multi-trauma patients improved their functional status and quality of life. A faster (maximum) recovery in functional status was observed for Fast Track at 6 months compared to 9 months for Care as Usual. At twelve months follow-up no differential effects between treatment conditions were found. TRIAL REGISTRATION: ISRCTN68246661.

Abnormal connectivity in the sensorimotor network predicts attention deficits in traumatic brain injury.

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 < 10-3) and a trend towards a significant effect of the DMN connectivity on attention (p = 0.058). A group-by-network interaction on attention was found in the sensorimotor network (p = 0.002). In TBI, attention was positively related to abnormal connectivity within the sensorimotor RSN, while in HC this relation was negative. Our results show altered patterns of functional connectivity after TBI. Attention impairments in TBI were associated with increased connectivity in the sensorimotor network. Further research is needed to test whether attention in TBI patients is directly affected by changes in functional connectivity in the sensorimotor network or whether the effect is actually driven by changes in the DMN.

The juvenile head trauma syndrome: a trauma triggered migraine?

BACKGROUND: The underlying mechanism of the juvenile head trauma syndrome (JHTS) is still uncertain, but it has been suggested that there is a role in cortical spreading depression, a phenomenon that is assumed to be a part of the pathophysiology of migraine. HYPOTHESIS: We postulate that children affected by the JHTS are more susceptible to cortical spreading depression, caused by a genetic etiology similar to genetic factors in migraine. METHODS: Children with the JHTS were selected and evaluated retrospectively in an observational case-control study in two Dutch trauma centers in the period between January 2008 and July 2012. RESULTS: We included 33 patients with the JHTS, who were accounted for approximately 2.5% of the total number (1,342) of children seen at the emergency department with a mild head trauma. The prevalence of migraine in cases compared with controls did not differ. The proportion of patients with a first-degree relative with migraine was significantly higher in cases compared with controls (odds ratio, 2.69; 95% confidence interval, 1.16-6.22; p = 0.010). CONCLUSION: The JHTS is a relatively rare phenomenon, seen in approximately 2.5% of all children seen at the emergency department with mild brain injury. This study demonstrates a significant relationship between the JHTS and a positive history of migraine in first-degree relatives.

The vegetative state: prevalence, misdiagnosis, and treatment limitations.

INTRODUCTION: Patients in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) open their eyes spontaneously, but show only reflexive behavior. Although VS/UWS is one of the worst possible outcomes of acquired brain injury, its prevalence is largely unknown. This study's objective was to map the total population of hospitalized and institutionalized patients in VS/UWS in the Netherlands: prevalence, clinical characteristics, and treatment limitations. METHODS: Nationwide point prevalence study on patients in VS/UWS at least 1 month after acute brain injury in hospitals, rehabilitation centers, nursing homes, institutions for people with intellectual disability, and hospices; diagnosis verification by a researcher using the Coma Recovery Scale-revised (CRS-r); gathering of demographics, clinical characteristics, and treatment limitations. RESULTS: We identified 33 patients in VS/UWS, 24 of whose diagnoses could be verified. Patients were on average 51 years old with a mean duration of VS/UWS of 5 years. The main etiology was hypoxia sustained during cardiac arrest and resuscitation. More than 50% of patients had not received rehabilitation services. Most were given life-sustaining treatment beyond internationally accepted prognostic boundaries regarding recovery of consciousness. Seventeen (39%) of 41 patients presumed to be in VS/UWS were found to be at least minimally conscious. CONCLUSIONS: Results translate to a prevalence of 0.1 to 0.2 hospitalized and institutionalized VS/UWS patients per 100,000 members of the general population. This small figure may be related to the legal option to withhold or withdraw life-sustaining treatment, including artificial nutrition and hydration. On the other hand, this study shows that in certain cases, physicians continue life-prolonging treatment for up to 25 years. Patients have poor access to rehabilitation and are at substantial risk for misdiagnosis.

Impact of depression and post-traumatic stress disorder on functional outcome and health-related quality of life of patients with mild traumatic brain injury.

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.