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Head Injury

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Head Injury
Author: David A Olson, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more... Updated: Sep 5, 2012

Background
Head injury can be defined as any alteration in mental or physical functioning related to a blow to the head. Loss of consciousness does not need to occur. The severity of head injuries is most commonly classified by the initial postresuscitation Glasgow Coma Scale (GCS) score, which generates a numerical summed score for eye, motor, and verbal abilities. Traditionally, a score of 13-15 indicates mild injury, a score of 9-12 indicates moderate injury, and a score of 8 or less indicates severe injury. In the last few years, however, some studies have included those patients with scores of 13 in the moderate category, while only those patients with scores of 14 or 15 have been included as mild.[1] Concussion and mild head injury are generally synonymous. Research on head injury has advanced considerably in the last decade. As is typical of many endeavors, these efforts have exposed the complexity of this condition more deeply and have helped researchers and physicians to abandon crude simplifications. This review concentrates primarily on current developments in the diagnosis and management of closed head injuries in adults.

Pathophysiology
Structural changes
Gross structural changes in head injury are common and often obvious both on autopsy and conventional neuroimaging. The skull can fracture in a simple linear fashion or in a more complicated depressed manner, in which bone fragments and pushes beneath the calvarial surface. In patients with mild head injury, a skull fracture markedly increases the chance of significant intracranial injury. Both direct impact and contrecoup injuries, in which the moving brain careens onto the distant skull opposite the point of impact, can result in focal bleeding beneath the calvaria. Such bleeding can result in an intracerebral focal contusion or hemorrhage as well as an extracerebral hemorrhage. Extracerebral hemorrhages are primarily subdural hemorrhages arising from tearing of bridging veins, but epidural hemorrhages from tearing of the middle meningeal artery or the diploic veins are also common. Occasionally, subdural hemorrhages can result from disruption of cortical arteries. This type of subdural hemorrhage is rapidly progressive and can occur after trivial head injury in elderly patients .[2] One study of CT images from 753 patients with severe head injury from the National Institute of Health Traumatic Coma Data Bank in the United States found evidence of intracranial hemorrhagic lesions in 27%. Traumatic
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subarachnoid hemorrhage was even more frequent and occurred in 39% of patients. Furthermore, diffuse cerebral edema also was present in 39%. Cerebral edema can be unilateral or diffuse and can occur even in the absence of intracranial bleeding. Severe brain edema probably occurs more commonly in children than in adults.[3] Neuronal loss is also important. A recent pathological study found that quantitative loss of neurons from the dorsal thalamus correlated with severe disability and vegetative state outcomes in patients with closed head injuries .[4] Finally, axonal injury increasingly has been recognized as a structural sequela of brain injury. The use of amyloid precursor protein staining has resulted in increased recognition of this form of injury. Using this technique, researchers have readily identified axonal injury in patients with mild head injury. Interestingly, a prominent locus of axonal damage has been the fornices, which are important for memory and cognition.[5] More severe and diffuse axonal injury has been found to correlate with vegetative states and the acute onset of coma following injury.[6]

Neurochemical changes
After traumatic brain injury, the brain is bathed with potentially toxic neurochemicals. Catecholamine surges have been documented in the plasma (higher catecholamine levels correlated with worse clinical outcomes) and in the cerebrospinal fluid (CSF) of patients with head injuries (higher CSF 5-hydroxyindole acetic acid (HIAA), the serotonin metabolite, correlated with worse outcomes).[7] Head injury causes release of free radicals and breakdown of membrane lipids. These lipids fragment into mediators of inflammation. The excitotoxic amino acids (ie, glutamate, aspartate) initiate a cascade of processes culminating in an increase in intraneuronal calcium and cell death. Researchers using a microdialysis technique have correlated high CSF levels of excitotoxic amino acids with poor outcomes in head injury.[8] Although neuroprotective strategies employing antiexcitotoxic pharmacotherapies were effective in diminishing the effects of experimental brain injuries in laboratory animals, clinical trials in humans generally have been disappointing.[9] These failures have prompted development of more complex models of neuronal injury and cell death. Recently, researchers have demonstrated that although certain types of glutamate antagonists may protect against acute cell death, they potentiate slowly progressive neuronal injury in experimental rodent models. Still others have found that low-dose glutamate administered before brain injury is somehow neuroprotective. Such dose and timing effects are only beginning to be understood.[10] Prostaglandins, inflammatory mediators produced by membrane lipid breakdown, are also elevated dramatically in the plasma of patients with moderate-to-severe head trauma during the first 2 weeks after injury. Patients with higher prostaglandin levels had significantly worse outcomes than those with more modest elevations. Furthermore, levels of a thromboxane metabolite, a potent vasoconstricting prostaglandin, were elevated disproportionately.[11] Such a process may underlie posttraumatic vasospasm, which has been documented in some, but not all, transcranial Doppler studies of patients with closed head injuries, even in patients without traumatic subarachnoid bleeds.[12] Recently, an increase in T cells reactive against myelin antigens was found in 10 patients with severe head injuries. Although the sample size was limited, those patients with increased T-cell reactivity had improved outcomes compared with their nonreactive counterparts, and a beneficial autoimmune response was proposed.[13] In addition to structural and chemical changes, gene expression is altered following closed head injury. Genes involving growth factors, hormones, toxin-binders, apoptosis (programmed cell death), and inflammation have all been implicated in rodent models. For example, in a mouse model of head injury, elevated levels of the transcription factor p53 were found. p53 translocates to the nucleus and initiates apoptosis or programmed cell death. Such a process could account for the delayed neuronal loss seen in head injuries.[14]

Secondary insults
Hypotension and hypoxia cause the most prominent secondary trauma-induced brain insults. Both hypoxia and hypotension had adverse impacts on outcomes of 716 patients with severe head injuries from the Traumatic Coma Data Bank in the United States. Efforts to limit hypoxic injury with in-field intubation have been unsuccessful. Indeed, a multicenter study of 4098 patients with severe traumatic brain injury found that in-field intubation was associated with a dramatic increase in death and poor long-term neurologic outcome, even after controlling for injury severity.[15] In the Trauma Coma Data Bank study, hypotension was even more significant than hypoxia and, by itself, was associated with a 150% increase in mortality rate. Systemic hypotension is critical because brain perfusion
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diminishes with lower somatic blood pressures. Brain perfusion (ie, cerebral perfusion pressure) is the difference between the mean arterial pressure and intracranial pressure. The intracranial pressure is increased in head injury by intracranial bleeding, cell death, and secondary hypoxic and ischemic injuries. Accordingly, another recent study reported that death and increased disability outcomes correlated with the durations of both systemic hypotension and elevated intracranial pressures.[16] Severe anemia is often coexistent with head injuries, but blood transfusions have been recently associated with increased mortality and complications among 1,250 ICU-admitted patients with brain injuries. This relationship held even after controlling for the degree of anemia.[17] Finally, posttraumatic cerebral infarction occurs in up to 12% of patients with moderate and severe head injuries and is associated with a decreased Glasgow Coma Scale, low blood pressure, and herniation syndromes.[18]

Epidemiology
Frequency
United States In the United States, 1.5 million individuals per year incur a head injury. Of these injuries, 75% are classified as mild. Between 1998 and 2000, the incidence of mild traumatic brain injury was 503 cases per 100,000 persons, with a doubling of this incidence in Native Americans and children. In 2003, elderly persons with head injuries exhibited a doubling in hospitalizations and deaths compared to the national average.[19] In 1995, hospitalization for brain injuries decreased 50% compared to 1980 data, primarily because of increased utilization of outpatient services for patients with minor head injuries. International European rates of hospitalization for head injury have ranged from 91 cases per 100,000 persons per year in Spain in 1988 to 313 cases per 100,000 persons per year in Scotland from 1974-1976.[20] In New Zealand, 782 cases per 100,000 of mild head injury were seen in hospitals or emergency rooms in 1986.[21] Head injury data are difficult to compare internationally for multiple reasons, including inconsistencies and complexities of diagnostic coding and inclusion criteria, case definitions, ascertainment criteria (for example, hospital admissions versus door-to-door surveys), transfers to multiple care facilities (for example, patient admissions may be counted more than once), and regional medical practices, such as the aforementioned recent development in the United States of more outpatient, as opposed to inpatient, services for those with mild head injuries. Adding to this complexity is the finding that some individuals with cognitive and emotional sequelae from mild head injury may not establish the casual connection between their injury and its consequences. Such patients may not seek treatment and may not be expressed in official demographic data.[22, 23]

Mortality/Morbidity
According to the CDC, 50,000 individuals die from traumatic brain injuries each year in the United States. Almost twice that number suffer permanent disability.

Race
A study of intentional head injury from Charlotte, North Carolina, found minority status was a major predictor of intentional head injury, even after controlling for other demographic factors.[24] Furthermore, worse clinical outcomes have been described for African American children with moderate-to-severe head injuries compared with their white counterparts.[25]

Sex
Men in the United States are nearly twice as likely to be hospitalized with a brain injury than women. This male predominance is found worldwide.
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Age
Approximately half of the patients admitted to a hospital for head injury are aged 24 years or younger.

Contributor Information and Disclosures

Author David A Olson, MD Clinical Neurologist, Dekalb Neurology Associates, Decatur, Georgia David A Olson, MD is a member of the following medical societies: American Academy of Neurology Disclosure: Nothing to disclose. Specialty Editor Board Joseph Carcione Jr, DO, MBA Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Florian P Thomas, MD, MA, PhD, Drmed Director, Regional MS Center of Excellence, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, and Sigma Xi Disclosure: Nothing to disclose. Chief Editor Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa Disclosure: Nothing to disclose.

References
1. Stein SC. Minor head injury: 13 is an unlucky number. J Trauma. Apr 2001;50(4):759-60. [Medline]. 2. Matsuyama T, Shimomura T, Okumura Y, et al. Acute subdural hematomas due to rupture of cortical arteries: a study of the points of rupture in 19 cases. Surg Neurol. May 1997;47(5):423-7. [Medline]. 3. Eisenberg HM, Gary HE Jr, Aldrich EF, et al. Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg. Nov 1990;73(5):688-98. [Medline].
emedicine.medscape.com/article/1163653-ov erv iew

4. Maxwell WL, MacKinnon MA, Smith DH, et al. Thalamic nuclei after human blunt head injury. J

4/16

12/20/12

4. Maxwell WL, MacKinnon MA, Smith DH, et al. Thalamic nuclei after human blunt head injury. J Neuropathol Exp Neurol. May 2006;65(5):478-88. [Medline]. 5. Blumbergs PC, Scott G, Manavis J, et al. Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury. J Neurotrauma. Aug 1995;12(4):565-72. [Medline]. 6. Jennett B, Adams JH, Murray LS, et al. Neuropathology in vegetative and severely disabled patients after head injury. Neurology. Feb 27 2001;56(4):486-90. [Medline]. 7. Markianos M, Seretis A, Kotsou S, et al. CSF neurotransmitter metabolites and short-term outcome of patients in coma after head injury. Acta Neurol Scand. Aug 1992;86(2):190-3. [Medline]. 8. Bullock R, Zauner A, Woodward JJ, et al. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. Oct 1998;89(4):507-18. [Medline]. 9. DeGraba TJ, Pettigrew LC. Why do neuroprotective drugs work in animals but not humans?. Neurol Clin. May 2000;18(2):475-93. [Medline]. 10. Jonas W, Lin Y, Tortella F. Neuroprotection from glutamate toxicity with ultra-low dose glutamate. Neuroreport. Feb 12, 2001;12(2):335-9. [Medline]. 11. Yang SY, Gao ZX. Determination and clinical significance of plasma levels of prostaglandins in patients with acute brain injury. Surg Neurol. Sep 1999;52(3):238-45. [Medline]. 12. Zubkov AY, Lewis AI, Raila FA, et al. Risk factors for the development of post-traumatic cerebral vasospasm. Surg Neurol. Feb 2000;53(2):126-30. [Medline]. 13. Cox AL, Coles AJ, Nortje J, et al. An investigation of auto-reactivity after head injury. J Neuroimmunol. May 2006;174(1-2):180-6. [Medline]. 14. Plesnila N, von Baumgarten L, Retiounskaia M, Engel D, Ardeshiri A, Zimmermann R, et al. Delayed neuronal death after brain trauma involves p53-dependent inhibition of NF-kappaB transcriptional activity. Cell Death Differ. Aug 2007;14(8):1529-41. [Medline]. 15. Wang HE, Peitzman AB, Cassidy LD, et al. Out-of-hospital endotracheal intubation and outcome after traumatic brain injury. Ann Emerg Med. Nov 2004;44(5):439-50. [Medline]. 16. Lannoo E, Van Rietvelde F, Colardyn F, et al. Early predictors of mortality and morbidity after severe closed head injury. J Neurotrauma. May 2000;17(5):403-14. [Medline]. 17. Salim A, Hadjizacharia P, DuBose J, Brown C, Inaba K, Chan L. Role of anemia in traumatic brain injury. J Am Coll Surg. Sep 2008;207(3):398-406. [Medline]. 18. Tian HL, Geng Z, Cui YH, Hu J, Xu T, Cao HL. Risk factors for posttraumatic cerebral infarction in patients with moderate or severe head trauma. Neurosurg Rev. Oct 2008;31(4):431-6; discussion 436-7. [Medline]. 19. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil. Nov-Dec 2006;21(6):544-8. [Medline]. 20. Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry. Apr 1996;60(4):362-9. [Medline]. 21. Wrightson P, Gronwall D. Mild head injury in New Zealand: incidence of injury and persisting symptoms. N Z Med J. Mar 27 1998;111(1062):99-101. [Medline]. 22. Thurman D, Guerrero J. Trends in hospitalization associated with traumatic brain injury. JAMA. Sep 8 1999;282(10):954-7. [Medline]. 23. Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. Feb 2004;(43 Suppl):28-60. [Medline]. 24. Wagner AK, Sasser HC, Hammond FM, et al. Intentional traumatic brain injury: epidemiology, risk factors, and associations with injury severity and mortality. J Trauma. Sep 2000;49(3):404-10. [Medline]. 25. Haider AH, Efron DT, Haut ER, DiRusso SM, Sullivan T, Cornwell EE 3rd. Black children experience worse clinical and functional outcomes after traumatic brain injury: an analysis of the National Pediatric emedicine.medscape.com/article/1163653-ov erv iew

5/16

12/20/12

Head Injury

worse clinical and functional outcomes after traumatic brain injury: an analysis of the National Pediatric Trauma Registry. J Trauma. May 2007;62(5):1259-62; discussion 1262-3. [Medline]. 26. Lau BC, Kontos AP, Collins MW, Mucha A, Lovell MR. Which On-field Signs/Symptoms Predict Protracted Recovery From Sport-Related Concussion Among High School Football Players?. Am J Sports Med. Nov 2011;39(11):2311-8. [Medline]. 27. Wu AP, Davidson T. Posttraumatic anosmia secondary to central nervous system injury. Am J Rhinol. Nov-Dec/2008;22:606-7. 28. Bernal-Sprekelsen M, Bleda-Vazquez C, Carrau RL. Ascending meningitis secondary to traumatic cerebrospinal fluid leaks. Am J Rhinol. Jul-Aug 2000;14(4):257-9. [Medline]. 29. Tien HC, Cunha JR, Wu SN, et al. Do trauma patients with a Glasgow Coma Scale score of 3 and bilateral fixed and dilated pupils have any chance of survival?. J Trauma. Feb 2006;60(2):274-8. [Medline]. 30. Mauritz W, Leitgeb J, Wilbacher I, et al. Outcome of brain trauma patients who have a Glasgow Coma Scale score of 3 and bilateral fixed and dilated pupils in the field. European Journal of Emergency Medicine. 2009;16:153-158. 31. Bhatoe HS. Primary brainstem injury: benign course and improved survival. Acta Neurochir (Wien). 1999;141(5):515-9. [Medline]. 32. Munjal SK, Panda NK, Pathak A. Dynamics of Hearing Status in Closed Head Injury. J Neurotrauma. Feb/2010;27:309-316. 33. Mackay LE, Morgan AS, Bernstein BA. Factors affecting oral feeding with severe traumatic brain injury. J Head Trauma Rehabil. Oct 1999;14(5):435-47. [Medline]. 34. Krauss JK, Trankle R, Kopp KH. Post-traumatic movement disorders in survivors of severe head injury. Neurology. Dec 1996;47(6):1488-92. [Medline]. 35. Matser JT, Kessels AG, Jordan BD, et al. Chronic traumatic brain injury in professional soccer players. Neurology. Sep 1998;51(3):791-6. [Medline]. 36. Lobato RD, Rivas JJ, Gomez PA, et al. Head-injured patients who talk and deteriorate into coma. Analysis of 211 cases studied with computerized tomography. J Neurosurg. Aug 1991;75(2):256-61. [Medline]. 37. Ellenberg JH, Levin HS, Saydjari C. Posttraumatic Amnesia as a predictor of outcome after severe closed head injury. Prospective assessment. Arch Neurol. Aug 1996;53(8):782-91. [Medline]. 38. Stuss DT, Binns MA, Carruth FG, et al. The acute period of recovery from traumatic brain injury: posttraumatic amnesia or posttraumatic confusional state?. J Neurosurg. Apr 1999;90(4):635-43. [Medline]. 39. Leininger BE, Gramling SE, Farrell AD, et al. Neuropsychological deficits in symptomatic minor head injury patients after concussion and mild concussion. J Neurol Neurosurg Psychiatry. Apr 1990;53(4):2936. [Medline]. 40. Crevits L, Hanse MC, Tummers P, et al. Antisaccades and remembered saccades in mild traumatic brain injury. J Neurol. Mar 2000;247(3):179-82. [Medline]. 41. Ruffolo LF, Guilmette TJ, Willis GW. Comparison of time and error rates on the trail making test among patients with head injuries, experimental malingerers, patients with suspect effort on testing, and normal controls. Clin Neuropsychol. May 2000;14(2):223-30. [Medline]. 42. Thomas KE, Stevens JA, Sarmiento K, Wald MM. Fall-related traumatic brain injury deaths and hospitalizations among older adults--United States, 2005. J Safety Res. 2008;39(3):269-72. [Medline]. 43. Hefny AF, Eid HO, Abu-Zidan FM. Severe tyre blast injuries during servicing. Injury. May 2009;40(5):4847. [Medline]. 44. Bhattacharjee Y. Neuroscience. Shell shock revisited: solving the puzzle of blast trauma. Science. Jan 25 2008;319(5862):406-8. [Medline].
emedicine.medscape.com/article/1163653-ov erv iew 6/16

12/20/12

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45. Belanger HG, Kretzmer T, Yoash-Gantz R, Pickett T, Tupler LA. Cognitive sequelae of blast-related versus other mechanisms of brain trauma. J Int Neuropsychol Soc. Jan 2009;15(1):1-8. [Medline]. 46. Reymond MA, Marbet G, Radu EW, et al. Aspirin as a risk factor for hemorrhage in patients with head injuries. Neurosurg Rev. 1992;15(1):21-5. [Medline]. 47. Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. Dec/2008;65:1303-8. 48. O'Phelan K, McArthur DL, Chang CW, Green D, Hovda DA. The impact of substance abuse on mortality in patients with severe traumatic brain injury. J Trauma. Sep 2008;65(3):674-7. [Medline]. 49. Talving P, Plurad D, Barmparas G, et al. Isolated severe traumatic brain injuries: association of blood alcohol levels with the severity of injuries and outcomes. J Trauma. Feb/2010;68:357-62. 50. Friedman G, Froom P, Sazbon L, et al. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology. Jan 15 1999;52(2):244-8. [Medline]. 51. Kutner KC, Erlanger DM, Tsai J, et al. Lower cognitive performance of older football players possessing apolipoprotein E epsilon4. Neurosurgery. Sep 2000;47(3):651-7; discussion 657-8. [Medline]. 52. Zhou W, Xu D, Peng X, Zhang Q, Jia J, Crutcher KA. Meta-analysis of APOE4 allele and outcome after traumatic brain injury. J Neurotrauma. Apr 2008;25(4):279-90. [Medline]. 53. Jordan BD. Genetic influences on outcome following traumatic brain injury. Neurochem Res. Apr-May 2007;32(4-5):905-15. [Medline]. 54. Tisdall M, Crocker M, Watkiss J, Smith M. Disturbances of sodium in critically ill adult neurologic patients: a clinical review. J Neurosurg Anesthesiol. Jan 2006;18(1):57-63. [Medline]. 55. Bacic A, Gluncic I, Gluncic V. Disturbances in plasma sodium in patients with war head injuries. Mil Med. Mar 1999;164(3):214-7. [Medline]. 56. Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma. Nov 2000;17(11):1029-39. [Medline]. 57. Halpern CH, Reilly PM, Turtz AR, Stein SC. Traumatic coagulopathy: the effect of brain injury. J Neurotrauma. Aug 2008;25(8):997-1001. [Medline]. 58. Herrmann M, Curio N, Jost S, et al. Release of biochemical markers of damage to neuronal and glial brain tissue is associated with short and long term neuropsychological outcome after traumatic brain injury. J Neurol Neurosurg Psychiatry. Jan 2001;70(1):95-100. [Medline]. 59. Stalnacke BM, Tegner Y, Sojka P. Playing soccer increases serum concentrations of the biochemical markers of brain damage S-100B and neuron-specific enolase in elite players: a pilot study. Brain Inj. Sep 2004;18(9):899-909. [Medline]. 60. Straume-Naesheim TM, Andersen TE, Jochum M, et al. Minor head trauma in soccer and serum levels of S100B. Neurosurgery. Jun/2008;62:1297-305. 61. Metting Z, Wilczak N, Rodiger LA, Schaaf JM, van der Naalt J. GFAP and S100B in the acute phase of mild traumatic brain injury. Neurology. May 1 2012;78(18):1428-33. [Medline]. 62. Haydel MJ, Preston CA, Mills TJ, et al. Indications for computed tomography in patients with minor head injury. N Engl J Med. Jul 13 2000;343(2):100-5. [Medline]. 63. Smits M, Dippel DW, Steyerberg EW, de Haan GG, Dekker HM, Vos PE. Predicting intracranial traumatic findings on computed tomography in patients with minor head injury: the CHIP prediction rule. Ann Intern Med. Mar 20 2007;146(6):397-405. [Medline]. 64. Wang MC, Linnau KF, Tirschwell DL, Hollingworth W. Utility of repeat head computed tomography after blunt head trauma: a systematic review. J Trauma. Jul 2006;61(1):226-33. [Medline]. 65. Smith-Bindman R, McCulloch CE, Ding A, Quale C, Chu PW. Diagnostic imaging rates for head injury in the ED and states' medical malpractice tort reforms. Am J Emerg Med. Jul 2011;29(6):656-64. [Medline].
emedicine.medscape.com/article/1163653-ov erv iew 7/16

12/20/12

Head Injury the ED and states' medical malpractice tort reforms. Am J Emerg Med. Jul 2011;29(6):656-64. [Medline].

66. Levin HS, Williams DH, Valastro M, et al. Corpus callosal atrophy following closed head injury: detection with magnetic resonance imaging. J Neurosurg. Jul 1990;73(1):77-81. [Medline]. 67. Pierallini A, Pantano P, Fantozzi LM, et al. Correlation between MRI findings and long-term outcome in patients with severe brain trauma. Neuroradiology. Dec 2000;42(12):860-7. [Medline]. 68. Rutgers DR, Toulgoat F, Cazejust J, Fillard P, Lasjaunias P, Ducreux D. White matter abnormalities in mild traumatic brain injury: a diffusion tensor imaging study. AJNR Am J Neuroradiol. Mar 2008;29(3):5149. [Medline]. 69. Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol. May 2008;29(5):967-73. [Medline]. 70. Fontaine A, Azouvi P, Remy P, et al. Functional anatomy of neuropsychological deficits after severe traumatic brain injury. Neurology. Dec 10 1999;53(9):1963-8. [Medline]. 71. Gowda NK, Agrawal D, Bal C, et al. Technetium Tc-99m ethyl cysteinate dimer brain single-photon emission CT in mild traumatic brain injury: a prospective study. AJNR Am J Neuroradiol. Feb 2006;27(2):447-51. [Medline]. 72. Garnett MR, Blamire AM, Rajagopalan B, et al. Evidence for cellular damage in normal-appearing white matter correlates with injury severity in patients following traumatic brain injury: A magnetic resonance spectroscopy study. Brain. Jul 2000;123 ( Pt 7):1403-9. [Medline]. 73. Vespa PM, Nuwer MR, Nenov V, et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg. Nov 1999;91(5):750-60. [Medline]. 74. Steinbaugh LA, Lindsell CJ, Shutter LA, Szaflarski JP. Initial EEG predicts outcomes in a trial of levetiracetam vs. fosphenytoin for seizure prevention. Epilepsy Behav. Mar 2012;23(3):280-4. [Medline]. 75. Carter BG, Butt W. Review of the use of somatosensory evoked potentials in the prediction of outcome after severe brain injury. Crit Care Med. Jan 2001;29(1):178-86. [Medline]. 76. Hortobgyi T, Wise S, Hunt N, Cary N, Djurovic V, Fegan-Earl A. Traumatic axonal damage in the brain can be detected using beta-APP immunohistochemistry within 35 min after head injury to human adults. Neuropathol Appl Neurobiol. Apr 2007;33(2):226-37. [Medline]. 77. Dressler J, Hanisch U, Kuhlisch E, et al. Neuronal and glial apoptosis in human traumatic brain injury. Int J Legal Med. 2007;121:365-375. 78. McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. Jul/2009;68:709-35. 79. White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg. Jun 2006;102(6):1836-46. [Medline]. 80. Roberts I. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. 2000;CD000033. [Medline]. 81. Shafi S, Diaz-Arrastia R, Madden C, Gentilello L. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma. Feb 2008;64(2):335-40. [Medline]. 82. Farahvar A, Gerber LM, Chiu YL, Carney N, Hrtl R, Ghajar J. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg. Aug 17 2012;[Medline]. 83. Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: management protocol and clinical results. J Neurosurg. Dec 1995;83(6):949-62. [Medline]. 84. White H, Venkatesh B. Cerebral perfusion pressure in neurotrauma: a review. Anesth Analg. Sep/2008;107:979-88.
emedicine.medscape.com/article/1163653-ov erv iew 8/16

12/20/12

85. The SAFE Study Investigators. Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury. NEJM. Aug/2007;357:874-84. 86. Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. Feb 22 2001;344(8):556-63. [Medline]. 87. Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev. Apr/2009;15:CD001048. 88. Clifton GL, Valadka A, Zygun D, et al. Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. Feb 2011;10(2):131-9. [Medline]. 89. Hrtl R, Gerber LM, Ni Q, Ghajar J. Effect of early nutrition on deaths due to severe traumatic brain injury. J Neurosurg. Jul 2008;109(1):50-6. [Medline]. 90. Reiff DA, Haricharan RN, Bullington NM, et al. Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacologic prophylaxis. J Trauma. May/2009;66:1436-40. 91. Depew AJ, Hu CK, Nguyen AC, et al. Thromboembolic prophylaxis in blunt traumatic intracranial hemorrhage: a retrospective review. Am Surg. OCt/2008;74:906-11. 92. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. Oct 9 2004;364(9442):1321-8. [Medline]. 93. Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. Aug 23 1990;323(8):497-502. [Medline]. 94. Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. Oct 1999;91(4):593-600. [Medline]. 95. Murray GD, Teasdale GM, Schmitz H. Nimodipine in traumatic subarachnoid haemorrhage: a re-analysis of the HIT I and HIT II trials. Acta Neurochir (Wien). 1996;138(10):1163-7. [Medline]. 96. Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol. Jan 2007;6(1):2938. [Medline]. 97. [Best Evidence] Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. Apr 2007;49(4):391-402, 402.e1-2. [Medline]. 98. Empey PE, McNamara PJ, Young B, et al. Cyclosporin A disposition following acute traumatic brain injury. J Neurotrauma. Jan 2006;23(1):109-16. [Medline]. 99. Maas AI, Murray G, Henney H, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol. Jan 2006;5(1):38-45. [Medline]. 100. Tapia-Perez JH, Sanchez-Aguilar M, Torres-Corzo JG, Gordillo-Moscoso A, Martinez-Perez P, Madeville P. Effect of rosuvastatin on amnesia and disorientation after traumatic brain injury (NCT003229758). J Neurotrauma. Aug 2008;25(8):1011-7. [Medline]. 101. Sullivan PG, Geiger JD, Mattson MP, et al. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol. Nov 2000;48(5):723-9. [Medline]. 102. Cirak B, Rousan N, Kocak A, et al. Melatonin as a free radical scavenger in experimental head trauma. Pediatr Neurosurg. Dec 1999;31(6):298-301. [Medline]. 103. Meythaler JM, Guin-Renfroe S, Grabb P, Hadley MN. Long-term continuously infused intrathecal baclofen for spastic-dystonic hypertonia in traumatic brain injury: 1-year experience. Arch Phys Med Rehabil. Jan 1999;80(1):13-9. [Medline]. 104. Richardson D, Sheean G, Werring D, et al. Evaluating the role of botulinum toxin in the management of focal hypertonia in adults. J Neurol Neurosurg Psychiatry. Oct 2000;69(4):499-506. [Medline].
emedicine.medscape.com/article/1163653-ov erv iew 9/16

12/20/12

focal hypertonia in adults. J Neurol Neurosurg Psychiatry. Oct 2000;69(4):499-506. [Medline]. 105. Plenger PM, Dixon CE, Castillo RM, et al. Subacute methylphenidate treatment for moderate to moderately severe traumatic brain injury: a preliminary double-blind placebo-controlled study. Arch Phys Med Rehabil. Jun 1996;77(6):536-40. [Medline]. 106. Kim YH, Ko MH, Na SY, et al. Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study. Clin Rehabil. Jan 2006;20(1):24-30. [Medline]. 107. Zhang L, Plotkin RC, Wang G, et al. Cholinergic augmentation with donepezil enhances recovery in shortterm memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil. Jul 2004;85(7):1050-5. [Medline]. 108. Khateb A, Ammann J, Annoni JM, Diserens K. Cognition-enhancing effects of donepezil in traumatic brain injury. Eur Neurol. 2005;54(1):39-45. [Medline]. 109. Bhatt M, Desai J, Mankodi A, Elias M, Wadia N. Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: a report on three patients. Mov Disord. Mar 2000;15(2):313-7. [Medline]. 110. Karli DC, Burke DT, Kim HJ, Calvanio R, Fitzpatrick M, Temple D. Effects of dopaminergic combination therapy for frontal lobe dysfunction in traumatic brain injury rehabilitation. Brain Inj. Jan 1999;13(1):63-8. [Medline]. 111. Nahas Z, Arlinghaus KA, Kotrla KJ, et al. Rapid response of emotional incontinence to selective serotonin reuptake inhibitors. J Neuropsychiatry Clin Neurosci. Fall 1998;10(4):453-5. [Medline]. 112. Fann JR, Uomoto JM, Katon WJ. Sertraline in the treatment of major depression following mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. Spring 2000;12(2):226-32. [Medline]. 113. Page S, Levine Peter. Forced use after TBI: promoting plasticity and function through practice. Brain Inj. Aug 2003;17(8):675-84. [Medline]. 114. Salazar AM, Warden DL, Schwab K, et al. Cognitive rehabilitation for traumatic brain injury: A randomized trial. Defense and Veterans Head Injury Program (DVHIP) Study Group. JAMA. Jun 21 2000;283(23):3075-81. [Medline]. 115. Zhao H, Bai XJ. Influence of operative timing on prognosis of patients with acute subdural hematoma. Chin J Traumatol. Oct/2009;12:296-8. 116. Croce MA, Dent DL, Menke PG, et al. Acute subdural hematoma: nonsurgical management of selected patients. J Trauma. Jun 1994;36(6):820-6; discussion 826-7. [Medline]. 117. Patel NY, Hoyt DB, Nakaji P, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma. Mar/2000;48:367-74. 118. Howard JL, Cipolle MD, Anderson M, Sabella V, Shollenberger D, Li PM. Outcome after decompressive craniectomy for the treatment of severe traumatic brain injury. J Trauma. Aug 2008;65(2):380-5; discussion 385-6. [Medline]. 119. Holder HD, Gruenewald PJ, Ponicki WR, et al. Effect of community-based interventions on high-risk drinking and alcohol-related injuries. JAMA. Nov 8 2000;284(18):2341-7. [Medline]. 120. Gentilello LM, Rivara FP, Donovan DM, et al. Alcohol interventions in a trauma center as a means of reducing the risk of injury recurrence. Ann Surg. Oct 1999;230(4):473-80; discussion 480-3. [Medline]. 121. Thompson DC, Rivara FP, Thompson R. Helmets for preventing head and facial injuries in bicyclists. Cochrane Database Syst Rev. 2000;CD001855. [Medline]. 122. Heng KW, Lee AH, Zhu S, et al. Helmet use and bicycle-related trauma in patients presenting to an acute hospital in Singapore. Singapore Med J. May 2006;47(5):367-72. [Medline]. 123. Lee BH, Schofer JL, Koppelman FS. Bicycle safety helmet legislation and bicycle-related non-fatal injuries in California. Accid Anal Prev. Jan 2005;37(1):93-102. [Medline]. 124. Donders J, Boonstra T. Correlates of invalid neuropsychological test performance after traumatic brain injury. Brain Inj. Mar 2007;21(3):319-26. [Medline].

Head Injury

emedicine.medscape.com/article/1163653-ov erv iew

10/16

injury. Brain Inj. Mar 2007;21(3):319-26. [Medline]. 125. Hutchison M, Comper P, Mainwaring L, Richards D. The influence of musculoskeletal injury on cognition: implications for concussion research. Am J Sports Med. Nov 2011;39(11):2331-7. [Medline]. 126. Dacey RG Jr, Alves WM, Rimel RW, et al. Neurosurgical complications after apparently minor head injury. Assessment of risk in a series of 610 patients. J Neurosurg. Aug 1986;65(2):203-10. [Medline]. 127. Deb S, Lyons I, Koutzoukis C. Neuropsychiatric sequelae one year after a minor head injury. J Neurol Neurosurg Psychiatry. Dec 1998;65(6):899-902. [Medline]. 128. Dikmen SS, Corrigan JD, Levin HS, et al. Cognitive Outcome Following Traumatic Brain Injury. J Head Trauma Rehabil. 2009;24:430-438. 129. Cantu RC. Second-impact syndrome. Clin Sports Med. Jan 1998;17(1):37-44. [Medline]. 130. McCrory P, Meeuwisse W, Johnston K, et al. Consensus statement on Concussion in Sport 3rd International Conference on Concussion in Sport held in Zurich, November 2008. Clin J Sport Med. May/2009;19:185-200. 131. McCrory PR, Berkovic SF. Second impact syndrome. Neurology. Mar 1998;50(3):677-83. [Medline]. 132. Mayers L. Return-to-Play Criteria After Athletic Concussion. Arch Neurol. Sept/2008;65:1158-1161. 133. Asikainen I, Kaste M, Sarna S. Early and late posttraumatic seizures in traumatic brain injury rehabilitation patients: brain injury factors causing late seizures and influence of seizures on long-term outcome. Epilepsia. May 1999;40(5):584-9. [Medline]. 134. Angeleri F, Majkowski J, Cacchio G, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. Sep 1999;40(9):1222-30. [Medline]. 135. Diaz-Arrastia R, Agostini MA, Frol AB, et al. Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults. Arch Neurol. Nov 2000;57(11):1611-6. [Medline]. 136. Obermann M, Holbe D, Katsarava Z. Post-traumatic headache. Expert Rev Neurother. Sep/2009;9:13611370. 137. Packard RC, Ham LP. Pathogenesis of posttraumatic headache and migraine: a common headache pathway?. Headache. Mar 1997;37(3):142-52. [Medline]. 138. Warner JS. Posttraumatic headache--a myth?. Arch Neurol. Dec 2000;57(12):1778-80; discussion 17801. [Medline]. 139. Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following traumatic brain injury. Arch Gen Psychiatry. Jan 2004;61(1):42-50. [Medline]. 140. Bilgic B, Baral-Kulaksizoglu I, Hanagasi H, et al. Obsessive-compulsive disorder secondary to bilateral frontal damage due to a closed head injury. Cogn Behav Neurol. Jun 2004;17(2):118-20. [Medline]. 141. Sachdev P, Smith JS, Cathcart S. Schizophrenia-like psychosis following traumatic brain injury: a chartbased descriptive and case-control study. Psychol Med. Feb 2001;31(2):231-9. [Medline]. 142. McCartan DP, Fleming FJ, Motherway C, Grace PA. Management and outcome in patients following head injury admitted to an Irish Regional Hospital. Brain Inj. Apr 2008;22(4):305-12. [Medline]. 143. van der Naalt J, van Zomeren AH, Sluiter WJ, et al. One year outcome in mild to moderate head injury: the predictive value of acute injury characteristics related to complaints and return to work. J Neurol Neurosurg Psychiatry. Feb 1999;66(2):207-13. [Medline]. 144. Chamelian L, Feinstein A. Outcome after mild to moderate traumatic brain injury: the role of dizziness. Arch Phys Med Rehabil. Oct 2004;85(10):1662-6. [Medline]. 145. Richmond R, Aldaghlas TA, Burke C, Rizzo AG, Griffen M, Pullarkat R. Age: Is It All in the Head? Factors Influencing Mortality in Elderly Patients With Head Injuries. J Trauma. Feb 17 2011;[Medline]. 146. Ritchie PD, Cameron PA, Ugoni AM, et al. A study of the functional outcome and mortality in elderly patients with head injuries. J Clin Neurosci. Jul 2000;7(4):301-4. [Medline].
emedicine.medscape.com/article/1163653-ov erv iew 11/16

12/20/12

Head Injury

147. Wade DT, King NS, Wenden FJ, et al. Routine follow up after head injury: a second randomised controlled trial. J Neurol Neurosurg Psychiatry. Aug 1998;65(2):177-83. [Medline]. 148. Schanke AK, Sundet K. Comprehensive driving assessment: neuropsychological testing and on- road evaluation of brain injured patients. Scand J Psychol. Jun 2000;41(2):113-21. [Medline]. 149. Bazarian JJ, McClung J, Shah MN, et al. Mild traumatic brain injury in the United States, 1998--2000. Brain Inj. Feb 2005;19(2):85-91. [Medline]. 150. Black K, Zafonte R, Millis S, et al. Sitting balance following brain injury: does it predict outcome?. Brain Inj. Feb 2000;14(2):141-52. [Medline]. 151. Blumbergs PC, Scott G, Manavis J, et al. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet. Oct 15 1994;344(8929):1055-6. [Medline]. 152. Bruce DA, Alavi A, Bilaniuk L, et al. Diffuse cerebral swelling following head injuries in children: the syndrome of "malignant brain edema". J Neurosurg. Feb 1981;54(2):170-8. [Medline]. 153. Cassidy JD, Carroll LJ, Cote P, et al. Effect of eliminating compensation for pain and suffering on the outcome of insurance claims for whiplash injury. N Engl J Med. Apr 20 2000;342(16):1179-86. [Medline]. 154. Centers for Disease Control and Prevention. Sports-related recurrent brain injuries--United States. MMWR Morb Mortal Wk ly Rep. Mar 14 1997;46(10):224-7. [Medline]. 155. Cernak I, Savic VJ, Kotur J, et al. Characterization of plasma magnesium concentration and oxidative stress following graded traumatic brain injury in humans. J Neurotrauma. Jan 2000;17(1):53-68. [Medline]. 156. Chesnut RM. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma. Aug/2008;65:500-1. 157. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. Feb 1993;34(2):216-22. [Medline]. 158. Chiu WT, Kuo CY, Hung CC, et al. The effect of the Taiwan motorcycle helmet use law on head injuries. Am J Public Health. May 2000;90(5):793-6. [Medline]. 159. Cho YW, Jang SH, Lee ZI, et al. Effect and appropriate restriction period of constraint-induced movement therapy in hemiparetic patients with brain injury: a brief report. NeuroRehabilitation. 2005;20(2):71-4. [Medline]. 160. Collins MW, Grindel SH, Lovell MR, et al. Relationship between concussion and neuropsychological performance in college football players. JAMA. Sep 8 1999;282(10):964-70. [Medline]. 161. Dharap SB, Khandkar AA, Pandey A, Sharma AK. Repeat CT scan in closed head injury. Injury. Mar 2005;36(3):412-6. [Medline]. 162. Drake AI, Gray N, Yoder S, et al. Factors predicting return to work following mild traumatic brain injury: a discriminant analysis. J Head Trauma Rehabil. Oct 2000;15(5):1103-12. [Medline]. 163. Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. Jul 1988;69(1):15-23. [Medline]. 164. Fabbri A, Servadei F, Marchesini G, et al. Early predictors of unfavorable outcome in subjects with moderate head injury in the emergency department. J Neurol Neurosurg Psychiatry. May/2008;79:567-73. 165. Feldman Z, Gurevitch B, Artru AA, et al. Effect of magnesium given 1 hour after head trauma on brain edema and neurological outcome. J Neurosurg. Jul 1996;85(1):131-7. [Medline]. 166. Gordon WA, Brown M, Sliwinski M, et al. The enigma of "hidden" traumatic brain injury. J Head Trauma Rehabil. Dec 1998;13(6):39-56. [Medline]. 167. Guerra WK, Gaab MR, Dietz H, et al. Surgical decompression for traumatic brain swelling: indications and results. J Neurosurg. Feb 1999;90(2):187-96. [Medline]. 168. Gusmao SN, Pittella JE. Extradural haematoma and diffuse axonal injury in victims of fatal road traffic accidents. Br J Neurosurg. Apr 1998;12(2):123-6. [Medline]. emedicine.medscape.com/article/1163653-ov erv iew

12/20/12

Head Injury

accidents. Br J Neurosurg. Apr 1998;12(2):123-6. [Medline]. 169. Haig AJ, Ruess JM. Recovery from vegetative state of six months' duration associated with Sinemet (levodopa/carbidopa). Arch Phys Med Rehabil. Dec 1990;71(13):1081-3. [Medline]. 170. Hall JR, Reyes HM, Horvat M, et al. The mortality of childhood falls. J Trauma. Sep 1989;29(9):1273-5. [Medline]. 171. Haltiner AM, Newell DW, Temkin NR, et al. Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. J Neurosurg. Oct 1999;91(4):588-92. [Medline]. 172. Hamill RW, Woolf PD, McDonald JV, et al. Catecholamines predict outcome in traumatic brain injury. Ann Neurol. May 1987;21(5):438-43. [Medline]. 173. Hanlon RE, Demery JA, Martinovich Z, et al. Effects of acute injury characteristics on neurophysical status and vocational outcome following mild traumatic brain injury. Brain Inj. Nov 1999;13(11):873-87. [Medline]. 174. Harders A, Kakarieka A, Braakman R. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. J Neurosurg. Jul 1996;85(1):82-9. [Medline]. 175. Homayoun P, Parkins NE, Soblosky J, et al. Cortical impact injury in rats promotes a rapid and sustained increase in polyunsaturated free fatty acids and diacylglycerols. Neurochem Res. Feb 2000;25(2):269-76. [Medline]. 176. Ikonomidou C, Stefovska V, Turski L. Neuronal death enhanced by N-methyl-D-aspartate antagonists. Proc Natl Acad Sci U S A. Nov 7 2000;97(23):12885-90. [Medline]. 177. Inamasu J, Hori S, Aoki K, et al. CT scans essential after posttraumatic loss of consciousness. Am J Emerg Med. Nov 2000;18(7):810-1. [Medline]. 178. Jordan BD, Relkin NR, Ravdin LD, et al. Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA. Jul 9 1997;278(2):136-40. [Medline]. 179. Keenan HT, Brundage SI, Thompson DC, et al. Does the face protect the brain? A case-control study of traumatic brain injury and facial fractures. Arch Surg. Jan 1999;134(1):14-7. [Medline]. 180. Knoller N, Levi L, Shoshan I, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med. Mar 2002;30(3):548-54. [Medline]. 181. Kobori N, Clifton GL, Dash P, et al. Altered expression of novel genes in the cerebral cortex following experimental brain injury. Brain Res Mol Brain Res. Aug 15 2002;104(2):148-58. [Medline]. 182. Kobrine AI, Timmins E, Rajjoub RK, et al. Demonstration of massive traumatic brain swelling within 20 minutes after injury. Case report. J Neurosurg. Feb 1977;46(2):256-8. [Medline]. 183. Lal S, Merbtiz CP, Grip JC. Modification of function in head-injured patients with Sinemet. Brain Inj. JulSep 1988;2(3):225-33. [Medline]. 184. Landau WM. Tizanidine and spasticity. Neurology. Dec 1995;45(12):2295-6. [Medline]. 185. Landy PJ. Neurological sequelae of minor head and neck injuries. Injury. Apr 1998;29(3):199-206. [Medline]. 186. Lane PL, Skoretz TG, Doig G, et al. Intracranial pressure monitoring and outcomes after traumatic brain injury. Can J Surg. Dec 2000;43(6):442-8. [Medline]. 187. Lang DA, Teasdale GM, Macpherson P, et al. Diffuse brain swelling after head injury: more often malignant in adults than children?. J Neurosurg. Apr 1994;80(4):675-80. [Medline]. 188. Levin HS, Gary HE Jr, Eisenberg HM, et al. Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. J Neurosurg. Nov 1990;73(5):699-709. [Medline]. 189. Levin HS, Mattis S, Ruff RM, et al. Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg. Feb 1987;66(2):234-43. [Medline]. 190. Levin HS, Williams DH, Eisenberg HM, et al. Serial MRI and neurobehavioural findings after mild to moderate closed head injury. J Neurol Neurosurg Psychiatry. Apr 1992;55(4):255-62. [Medline]. emedicine.medscape.com/article/1163653-ov erv iew

13/16

12/20/12

Head Injury

moderate closed head injury. J Neurol Neurosurg Psychiatry. Apr 1992;55(4):255-62. [Medline]. 191. Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet. Mar 10 2001;357(9258):771-2. [Medline]. 192. Macfarlane DP, Nicoll JA, Smith C, et al. APOE epsilon4 allele and amyloid beta-protein deposition in long term survivors of head injury. Neuroreport. Dec 16 1999;10(18):3945-8. [Medline]. 193. Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. Feb 20 1997;336(8):540-6. [Medline]. 194. Marmarou A, Anderson RL, Ward JD, et al. Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg. 1991;75:S59-66. 195. Marshall LF, Gautille T, Klauber MR, et al. The outcome of severe head injury. J Neurosurg. 1991;75:S2836. 196. Mayers l. Return-to-Play Criteria after Athletic Concussion. Archives of Neurology. Sep/2008;65:11581161. 197. Miller EC, Derlet RW, Kinser D. Minor head trauma: Is computed tomography always necessary?. Ann Emerg Med. Mar 1996;27(3):290-4. [Medline]. 198. Mittenberg W, Strauman S. Diagnosis of mild head injury and the postconcussion syndrome. J Head Trauma Rehabil. Apr 2000;15(2):783-91. [Medline]. 199. Mosimann UP, Muri RM, Felblinger J, et al. Saccadic eye movement disturbances in whiplash patients with persistent complaints. Brain. Apr 2000;123 ( Pt 4):828-35. [Medline]. 200. Murray JA, Demetriades D, Berne TV, et al. Prehospital intubation in patients with severe head injury. J Trauma. Dec 2000;49(6):1065-70. [Medline]. 201. Nagy KK, Joseph KT, Krosner SM, et al. The utility of head computed tomography after minimal head injury. J Trauma. Feb 1999;46(2):268-70. [Medline]. 202. Owings JT, Wisner DH, Battistella FD, et al. Isolated transient loss of consciousness is an indicator of significant injury. Arch Surg. Sep 1998;133(9):941-6. [Medline]. 203. Packard RC, Ham LP. Posttraumatic headache. J Neuropsychiatry Clin Neurosci. Summer 1994;6(3):22936. [Medline]. 204. Palmer AM, Marion DW, Botscheller ML, et al. Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J Neurochem. Dec 1993;61(6):2015-24. [Medline]. 205. Patel NY, Hoyt DB, Nakaji P, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma. Mar 2000;48(3):367-74; discussion 374-5. [Medline]. 206. Paterakis K, Karantanas AH, Komnos A, et al. Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase. J Trauma. Dec 2000;49(6):1071-5. [Medline]. 207. Pop E. Dexanabinol Pharmos. Curr Opin Investig Drugs. Dec 2000;1(4):494-503. [Medline]. 208. Procaccio F, Stocchetti N, Citerio G, et al. Guidelines for the treatment of adults with severe head trauma (part II). Criteria for medical treatment. J Neurosurg Sci. Mar 2000;44(1):11-8. [Medline]. 209. Report of the Quality Standards Subcommittee, American Academy of Neurology. Practice parameter: the management of concussion in sports (summary statement). Report of the Quality Standards Subcommittee. Neurology. Mar 1997;48(3):581-5. [Medline]. 210. Rugg-Gunn FJ, Symms MR, Barker GJ, et al. Diffusion imaging shows abnormalities after blunt head trauma when conventional magnetic resonance imaging is normal. J Neurol Neurosurg Psychiatry. Apr 2001;70(4):530-3. [Medline]. 211. Salmond CH, Menon DK, Chatfield DA, et al. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage. Jan 1 2006;29(1):117-24. [Medline]. 212. Signoretti S, Marmarou A, Tavazzi B, et al. The protective effect of cyclosporin A upon N-acetylaspartate and mitochondrial dysfunction following experimental diffuse traumatic brain injury. J Neurotrauma. Sep14/16 emedicine.medscape.com/article/1163653-ov erv iew

and mitochondrial dysfunction following experimental diffuse traumatic brain injury. J Neurotrauma. Sep 2004;21(9):1154-67. [Medline]. 213. Sloan RL, Brown KW, Pentland B. Fluoxetine as a treatment for emotional lability after brain injury. Brain Inj. Jul-Aug 1992;6(4):315-9. [Medline]. 214. Snoek JW, Minderhoud JM, Wilmink JT. Delayed deterioration following mild head injury in children. Brain. Mar 1984;107 ( Pt 1):15-36. [Medline]. 215. Speech TJ, Rao SM, Osmon DC, et al. A double-blind controlled study of methylphenidate treatment in closed head injury. Brain Inj. Jul-Aug 1993;7(4):333-8. [Medline]. 216. Struchen MA, Hannay HJ, Contant CF, et al. The relation between acute physiological variables and outcome on the Glasgow Outcome Scale and Disability Rating Scale following severe traumatic brain injury. J Neurotrauma. Feb 2001;18(2):115-25. [Medline]. 217. Sturmi JE, Smith C, Lombardo JA. Mild brain trauma in sports. Diagnosis and treatment guidelines. Sports Med. Jun 1998;25(6):351-8. [Medline]. 218. Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death?. J Neurosci Res. Jan 1-15 2005;79(1-2):231-9. [Medline]. 219. Teasdale GM. Head injury. J Neurol Neurosurg Psychiatry. May 1995;58(5):526-39. [Medline]. 220. The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Role of steroids. J Neurotrauma. Jun-Jul 2000;17(6-7):531-5. [Medline]. 221. The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Use of barbiturates in the control of intracranial hypertension. J Neurotrauma. Jun-Jul 2000;17(6-7):527-30. [Medline]. 222. Thurman DJ, Alverson C, Dunn KA, et al. Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehabil. Dec 1999;14(6):602-15. [Medline]. 223. Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. Jan 25 2000;54(2):340-5. [Medline]. 224. van Reekum R, Cohen T, Wong J. Can traumatic brain injury cause psychiatric disorders?. J Neuropsychiatry Clin Neurosci. Summer 2000;12(3):316-27. [Medline]. 225. Velmahos GC, Jindal A, Chan LS, et al. "Insignificant" mechanism of injury: not to be taken lightly. J Am Coll Surg. Feb 2001;192(2):147-52. [Medline]. 226. Wesson D, Spence L, Hu X, et al. Trends in bicycling-related head injuries in children after implementation of a community-based bike helmet campaign. J Pediatr Surg. May 2000;35(5):688-9. [Medline]. 227. Whelan FJ, Walker MS, Schultz SK. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. Sep 2000;12(3):131-5. [Medline]. 228. Whyte J, Hart T, Schuster K, et al. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. Nov-Dec 1997;76(6):440-50. [Medline]. 229. Wilberger JE Jr, Harris M, Diamond DL. Acute subdural hematoma: morbidity, mortality, and operative timing. J Neurosurg. Feb 1991;74(2):212-8. [Medline]. 230. Withaar FK, Brouwer WH, van Zomeren AH. Fitness to drive in older drivers with cognitive impairment. J Int Neuropsychol Soc. May 2000;6(4):480-90. [Medline]. 231. Young B, Runge JW, WebMD, LLC Medscape Reference 2011 Waxman KS, et al. Effects of pegorgotein on neurologic outcome of patients with severe head injury. A multicenter, randomized controlled trial. JAMA. Aug 21 1996;276(7):538-43. [Medline]. 232. Zafonte RD, Mann NR. Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia. Arch Phys Med Rehabil. May 1997;78(5):540-2. [Medline].

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Head hyponatremia. Arch Phys Med Rehabil.Injury 1997;78(5):540-2. [Medline]. May

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