A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator

for the Pediatric Emergency Research Canada (PERC) Concussion Team IMPORTANCE Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCEA clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

Normative studies of variability in performance by healthy adults on neuropsychological batteries are reviewed. Regarding test score scatter, normative participants often have large discrepancies between best and worst scores. When "abnormality" was defined as a score more than one standard deviation below the mean, in test batteries with at least 20 measures, the great majority of normative participants had one or more abnormalities. Restricting samples to participants with above average IQ or educational levels and using more conservative definitions of abnormality, such as two standard deviations below the mean did not eliminate the presence of abnormal scores. We conclude that abnormal performance on some proportion of neuropsychological tests in a battery is psychometrically normal. Abnormalities do not necessarily signify the presence of acquired brain dysfunction because low scores and large intraindividual variability often are characteristic of healthy adults. We recommend that test battery developers provide data on the amount of variability in normal samples and also provide base rate tables with false positive rates that can be used clinically when interpreting test performance.

This study illustrates the importance of analysing individual athletes' test data because group analyses can obscure slow recovery in a substantial minority of athletes.

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The psychometric criterion of mild cognitive impairment (MCI) generally involves having an unusually low score on memory testing (i.e., 21.5 SDs). However, healthy older adults can obtain low scores, particularly when multiple memory measures are administered. In turn, there is a substantial risk of psychometrically misclassifying MCI in healthy older adults. This study examined the base rates of low memory scores in older adults (55-87 years; n 5 550) from the Wechsler Memory Scale-Third Edition (WMS-III; Wechsler, 1997b) standardization sample. The WMS-III consists of four co-normed episodic memory tests (i.e., Logical Memory, Faces, Verbal Paired Associates, and Family Pictures) that yield eight age-and demographically-adjusted standard scores (Auditory Recognition and Working Memory tests not included). When the eight age-adjusted scores were examined simultaneously, 26% of older adults had one or more scores at or below the 5th percentile (i.e., 21.5 SDs). On the eight demographicallyadjusted scores, 39% had at least one score at or below the 5th percentile. There was an inverse relationship between intellectual abilities and prevalence of low memory scores, particularly with the age-adjusted WMS-III scores. Understanding the base rates of low scores can reduce the overinterpretation of low memory scores and minimize false-positive misclassification. (JINS, 2008, 14, 463-478.)

When assessing older adults for mild cognitive impairment (MCI) or dementia, it is important to understand how often low memory scores are obtained in healthy people in order to minimize false positive diagnoses. This study examines the base rates of low memory scores in older adults across a battery of memory tests. Participants included older adults (55-79 years; N = 742) from the Neuropsychological Assessment Battery (NAB; Stern and White, 2003a) standardization sample. The NAB Memory Module consists of four co-normed memory tests (i.e., List Learning, Shape Learning, Story Learning, and Daily Living Memory) yielding 10 demographically corrected T-scores. When all 10 T-scores were examined simultaneously, 55.5% of older adults had one or more scores one standard deviation (SD) below the mean. At <1.5 SDs, 30.8% of healthy older adults obtained one or more low memory scores. Obtaining low memory scores occurs more often with lesser intellectual abilities. For example, 56.5% of older adults with low average intellectual abilities obtained one or more low memory scores (<1.5 SDs) compared to 21.1% with high average intellectual abilities. Understanding the base rates of low scores can reduce over-interpretation of isolated low memory scores and minimize false positive diagnoses of MCI.

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