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Gordon D. Murray, Paul M. Brennan, and Graham M. Teasdale

-injury databases. The CRASH (Corticosteroid Randomisation After Significant Head Injury) study recruited 10,008 adults with head injury and GCS scores of 14 or less from 239 hospitals in 49 countries. 43 The IMPACT (International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury) prognostic model was developed using data from 11,989 patients who had sustained moderate (GCS scores 9–12) or severe (GCS scores 3–8) traumatic brain injuries (TBIs): the data had been collected prospectively during 11 different studies. 28 The present study used pooled data derived

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Paul M. Brennan, Gordon D. Murray, and Graham M. Teasdale

Prognosis and Clinical Trials in TBI). 10 In the CRASH study 10,008 adults with head injury were recruited from 239 hospitals in 49 countries. The IMPACT database, on the other hand, contains data on 11,989 patients with traumatic brain injury (TBI), which were collected prospectively for 11 different studies including 8 randomized controlled trials and 3 epidemiological studies. GCS Score and Pupil Reactivity From the CRASH and IMPACT databases we identified patients for whom both GCS score and pupil reactivity information were available. In the CRASH study, the eye

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Vengalathur Ganesan Ramesh

TO THE EDITOR: The ability to predict the outcome after traumatic brain injury (TBI) adds to the clinical armamentarium of everyone involved in the care of such patients. This ability helps not only in planning better and more aggressive care of those patients with predicted borderline prognosis, but also in preparing the patient’s family in cases with grave prognosis. I read with interest the articles by Brennan et al. 1 and Murray et al. 2 ( Brennan PM, Murray GD, Teasdale GM: Simplifying the use of prognostic information in traumatic brain injury. Part 1

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Davi J. Fontoura Solla, Manoel Jacobsen Teixeira, and Wellingson Silva Paiva

TO THE EDITOR: We read with great interest the articles recently published by Brennan et al. 2 and Murray et al. 4 concerning the Glasgow Coma Scale-Pupils (GCS-P) score, and we commend the authors on the efforts undertaken to improve traumatic brain injury (TBI) prognostication ( Brennan PM, Murray GD, Teasdale GM: Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg 128 :1612–1620, June 2018 ; Murray GD, Brennan PM, Teasdale GM: Simplifying the use of

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Paul M. Brennan, Gordon D. Murray, and Graham M. Teasdale

simple, quick arithmetic calculation, to more complex multivariate models, such as the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT). 12 A number of imputation methods for dealing with missing GCS data have been proposed, although alternative approaches to imputation can result in different predictions of mortality. 13–16 These imputation strategies are principally used to support the analysis of trauma registry data, in which missing GCS observations can be as high as 20% 13 and are most

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Laura E. L. Pettigrew, J. T. Lindsay Wilson, and Graham M. Teasdale

: Management of Head Injuries. Philadelphia: FA Davis, 1981 12. Kreutzer JS , Marwitz JH , Witol AD : Interrelationships between crime, substance abuse, and aggressive behaviours among persons with traumatic brain injury. Brain Inj 9 : 757 – 768 , 1995 Kreutzer JS, Marwitz JH, Witol AD: Interrelationships between crime, substance abuse, and aggressive behaviours among persons with traumatic brain injury. Brain Inj 9: 757–768, 1995 13. Kreutzer JS , Wehman PH , Harris JA , et al : Substance

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Michael C. Wallace, Graham M. Teasdale, and James McCulloch

. Dewar D , Wallace MC , Kurumaji A , et al : Alterations in the N-methyl-D-aspartate receptor complex following focal cerebral ischemia. J Cereb Blood Flow Metab 9 : 709 – 712 , 1989 Dewar D, Wallace MC, Kurumaji A, et al: Alterations in the N-methyl-D-aspartate receptor complex following focal cerebral ischemia. J Cereb Blood Flow Metab 9: 709–712, 1989 11. Faden AI , Demediuk P , Panter SS , et al : The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science

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Imran Liaquat, Laurence T. Dunn, James A. R. Nicoll, Graham M. Teasdale, and John D. Norrie

does not influence the likelihood of suffering a mass lesion after traumatic brain injury. Linear regression analyses demonstrate that the presence of an APOE-ϵ4 allele is an independent predictor of a larger intracranial hematoma after head injury, compared with the presence of its isoforms. The larger hematomas found in patients with the APOE-ϵ4 allele may partly explain the poorer outcomes after head injury observed in these patients. Acknowledgments We thank Professor Gordon Murray for initial statistical advice and Mrs. Janice Stewart for the APOE

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M. Ross Bullock, Randall E. Merchant, Sung C. Choi, Charlotte B. Gilman, Jeffrey S. Kreutzer, Anthony Marmarou, and Graham M. Teasdale

Under the auspices of the American Brain Injury Consortium and the Joint Section of Neurotrauma and Critical Care of the American Association of Neurological Surgeons, the authors have reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI.

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A new experimental model of contusion in the rat

Histopathological analysis and temporal patterns of cerebral blood flow disturbances

Peter Mathew, Ross Bullock, David I. Graham, William L. Maxwell, Graham M. Teasdale, and James McCulloch

injury in humans: an analysis of 45 cases. Ann Neurol 12 : 557 – 563 , 1982 Adams JH, Graham DI, Murray LS, et al: Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases. Ann Neurol 12: 557–563, 1982 4. Bouma GJ , Muizelaar JP , Choi SC , et al : Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. J Neurosurg 75 : 685 – 693 , 1991 Bouma GJ, Muizelaar JP, Choi SC, et al: Cerebral circulation and metabolism after severe