Head Injury Treatment & Management
- Author: David A Olson, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more...
In the setting of acute head injury, give priority to the immediate assessment and stabilization of the airway and circulation. Despite the fact that prehospital intubation has become common, at least one study has reported a higher rate of mortality in patients intubated in the field than in those intubated in the hospital setting. In this study, however, more critically ill patients required in-field intubation.
Following stabilization, direct attention to prevention of secondary injury. Keep mean arterial pressures above 90 mm Hg; arterial saturations should be greater than 90%. Urgent CT scanning is a priority.
Next, focus attention on reducing intracranial pressure, since elevated intracranial pressure is an independent predictor of poor outcome. If the intracranial pressure rises above 20-25 mm Hg, intravenous mannitol, CSF drainage, and hyperventilation can be used. Hypertonic saline has also been used in lieu of mannitol to lower intracranial pressure, but more definitive studies are needed. If the intracranial pressure does not respond to these conventional treatments, high-dose barbiturate therapy is permissible, despite the fact that no evidence currently suggests that barbiturate treatment actually improves outcomes. (Its blood pressure–lowering effects may be detrimental.)
Interestingly, a 2008 study utilizing the National Trauma Data Bank retrospectively uncovered a 45% reduction in survival in patients who underwent intracranial pressure monitoring. These results had been called into question because of a dearth of clinical and neuroimaging data, but a 2012 prospective study of 2134 patients with severe traumatic brain injury found improved 2-week survival in patients who underwent ICP monitoring compared to those who were not monitored. Nevertheless, the non-monitored patients may have had a more grave prognosis to start with because they were significantly older and more likely to have had pupillary abnormalities, factors which could have impacted the treating physicians' decision to implement ICP monitoring.
Another approach used by some clinicians is to focus primarily on improving cerebral perfusion pressure as opposed to intracranial pressure in isolation. One study reported that 80% of patients with severe head injuries experienced recoveries with no or little disability after volume expansion, mannitol, CSF drainage, and vasopressors were used to maintain a cerebral perfusion pressure of at least 70 mm Hg. Other studies have found higher perfusion pressures were associated with more complications and have recommended maintaining a cerebral perfusion pressure of 50-70 mm Hg.
The question whether saline or albumin fluid resuscitation would maximize cerebral perfusion pressure and lead to improve outcomes lead to a large, double-blind, randomized controlled study of 460 patients with Glasgow Coma Scale scores < 13 who also had abnormal head CT scan results. A post-hoc 2-year follow-up demonstrated increased mortality in those receiving albumin as opposed to saline.
Although hypothermic therapy initially appeared promising, and despite the fact that hypothermia decreases intracranial pressure, a large randomized study of 392 patients with head injuries recently demonstrated that hypothermic therapy does not improve outcomes. In addition, a post-hoc analysis found that the rewarming of patients with head injury who arrived in the emergency department already hypothermic was likely detrimental. Furthermore, a current review of 23 randomized, controlled trials concluded that this therapy was of no benefit.
Acute hypothermic treatment has been found to worsen outcomes in patients with diffuse head injuries but to improve outcomes in patients with surgically-evacuated hematomas. This indicates a potential benefit in this subgroup; however, further prospective studies are needed.
Head injury induces a hypermetabolic state and early nutritional interventions may be as critical as cerebral perfusion pressure. Parental or enteral feedings reduced mortality by at least 50% in one study when given early in the course of severe head injury.
As mentioned previously, head injury may alter coagulation parameters, and this can raise the risk of deep venous thrombosis to as much as 15% if no pharmacologic prophylaxis is given within the first 48 hours. The risk of extension of intracranial bleeding needs to be balanced with the benefits of thromboembolic prevention. A retrospective review suggested that early prophylaxis is safe because there was no difference between intracranial hemorrhage progression in patients with head injury who received enoxaparin or heparin within the first 3 days versus later in the course of their hospitalization. Further studies, of course, are required.
Steroids have demonstrated no benefit in the treatment of acute head injury. A 2004 multicenter European randomized trial of steroids versus placebo found a higher mortality after only 2 weeks in the steroid-treated patients.
Phenytoin has demonstrated efficacy in controlling early posttraumatic seizures, but mortality rates, surprisingly, were unaffected by this benefit. In 1 study, approximately 2.5% of patients treated with phenytoin had an allergic reaction to the drug during the first 2 weeks of therapy. A trial of valproate in early seizure prophylaxis showed a trend toward an increased mortality rate. Anticonvulsant therapy, if used, should be discontinued after 1-2 weeks unless further seizures supervene.
Finally, as stated previously, neuroprotective agents mostly have failed to improve the outcomes of patients with brain injury. However, the calcium channel blocker nimodipine was successful in reducing rates of death and severe disability when instituted acutely in patients with head injuries and traumatic subarachnoid hemorrhages, despite its failure to improve outcomes in 2 large trials of patients with all types of traumatic intracranial injuries.
Although numerous synthetic neuroprotective agents are under development, several existing substances have shown promise, but other agents have been disappointing.
Because of its excitotoxic blocking properties, magnesium chloride has been used to reduce cortical injury in experimentally brain-injured rats. Unfortunately, a human double-blind study of 499 patients with moderate or severe head injury failed to show benefit; the magnesium-treated patients actually did worse. One potential confounder in this study was vigilance and aggressive repletion of hypomagnesemia in controls.
Progesterone given intravenously in a phase II, randomized, double-blind, placebo-controlled trial of 100 patients with moderate and severe head injury showed no adverse effects and reduced 30-day mortality by 57%. Unfortunately, worse outcomes were seen in the treated group with severe head injuries as measured by the extended Glasgow Outcome Score, perhaps because of the increased survivorship of sicker patients.
Experimental brain injury creates permeability in mitochondrial membranes, which contributes to cell death by causing calcium effluxes and energy depletion. Cyclosporin inhibits mitochondrial permeability and has been used in a phase II study of patients with traumatic brain injuries. Further trials are planned.
Cannabinoids also protect against excitotoxicity, but disappointingly, in a recent phase 3 trial, dexanabinol, a weak N -methyl-D-aspartic acid (NMDA) antagonist, showed no efficacy in outcome improvement when given within 6 hours to patients with severe closed head injuries.
Rosuvastatin given in the acute phase of moderate head injury significantly reduced amnesia in a double-blind placebo-controlled study of 34 patients.
Animal studies of some health food supplements may lead to new directions. The dietary supplement creatine, when fed to rats for 4 weeks prior to an experimental brain injury, reduced cortical damage by 50%, primarily through stabilizing mitochondrial functioning. Melatonin is a free radical scavenger, and when injected early in brain-injured rats, it significantly reduced levels of lipid breakdown products.
Hypertonicity from spasticity or dystonia with attendant muscle spasms is often disabling. Although dantrolene, baclofen, diazepam, and tizanidine are current oral medication approaches to this problem, baclofen and tizanidine are customarily preferred because of their more favorable side effect profiles.
When using these agents, careful evaluation of functional status and symptom relief is a priority since adverse effects such as sedation may be pronounced.
Intrathecal baclofen is a newer approach with reported efficacy and minimal adverse effects. One study of 17 patients with traumatic brain injuries showed improved motor tone and decreased muscle spasms with intrathecal baclofen, but whether these benefits will translate into improved functioning remains unknown.
Botulinum toxin also has shown promise in decreasing hypertonia in patients with head injuries, primarily by improving passive range of motion rather than by decreasing functional disability.
Solid data on cognitive enhancing medications for patients with head injury are lacking. Typically, only small numbers of subjects have been used and demonstrable functional improvement has been only marginally convincing.
Despite these drawbacks, one double-blind, placebo-controlled study of methylphenidate demonstrated improved motor outcomes and attention in patients with head injuries during active treatment, but only 6 patients completed each 30-day treatment arm. A 2006 double-blind, placebo-controlled study of 18 patients with closed head injuries treated with a single dose of 20 mg of methylphenidate achieved significant improvement in reaction times on a working memory test, but no other cognitive tasks significantly benefited.
Donepezil treatment significantly improved visual and verbal memory as well as attentional deployment in 18 patients with head injuries of all levels of severity in a 2004 double-blind, placebo-controlled study. Other less rigorous studies have also reported cognitive improvements in donepezil-treated, head-injured patients.
Anecdotal reports exist of dramatic alerting responses to both levodopa and methylphenidate in patients with vegetative or comatose states. Levodopa treatment has also resulted in improvement in patients with akinesia and rigidity secondary to traumatic substantia nigral damage. Furthermore, levodopa has even produced qualitative cognitive improvements in a small number of head-injured patients.
Emotional lability and the pathologic laughing and crying associated with pseudobulbar palsy reportedly have responded rapidly and exquisitely to selective serotonin reuptake inhibitors. Sertraline has shown efficacy in depression in mild head injury. Treat other possible psychiatric complications of head injury on a patient-by-patient basis, since no extensive pharmacologic trials of this dimension of head injury have been conducted.
Although a full review of nonmedical therapies is beyond the scope of this article, some promising new developments have occurred in both physical and cognitive therapies.
Constraint-induced movement therapy is a form of physical therapy that emphasizes using the paralyzed arm and minimizes reliance on the unaffected extremity (patients commonly wear mittens on their unaffected arm for several hours a day). This form of treatment has resulted in significantly improved function of the paralyzed arm when used in small numbers of brain-injured patients 1-6 years after their injury.
In a randomized trial in 120 military personnel with moderate-to-severe head injuries, in-hospital cognitive rehabilitation proved unsuccessful compared to a limited in-home program, but a subgroup post hoc analysis indicated that patients with unconsciousness lasting 1 hour or more had a greater functional recovery with in-hospital cognitive rehabilitation than those in the control group.
Traditionally, the prompt surgical evacuation of subdural hematomas in less than 4 hours was believed to be a major determinant of an optimal outcome. Indeed, a recent publication found a delay in surgery for acute subdural hematomas of over 5 hours was associated with increased mortality. Nevertheless, other recent investigations have emphasized that the extent of the original intracranial injury and the generated intracranial pressures may be more important than the timing of surgery.
For example, 70% of 83 patients with GCS scores of 11-15 who had subdural hematomas less than 1 cm in width and no cisternal effacement on neuroimaging or focal neurological deficits were successfully managed nonoperatively with only 6% eventually requiring surgery. 
Another study of 462 patients with head injuries with CT-imaged intracranial hematomas who were treated nonoperatively found that only approximately 10% progressed clinically and eventually required surgery. Frontal parenchymal hematomas were more likely to require eventual surgery. 
Decompressive craniectomies are sometimes advocated for patients with increased intracranial pressure refractory to conventional medical treatment. Of 40 patients with severe head injury who underwent this procedure (some for ICP elevations in isolation and some for ICP elevations with mass lesions), 30% had a favorable long-term outcome.  At least 2 major randomized clinical trials of this intervention are now underway.
The operative and nonoperative management of intracranial injuries is an ever-evolving area of study and, at present, more a matter of neurosurgical judgment than hard and fast decision rules.
In the acute setting, a consultation with a neurosurgeon is critical for patients with moderate or severe head injuries, focal neurological findings, or intracranial pathology identified on neuroimaging.
In the acute setting, nasogastric feedings may need to be initiated for patients with significant head injuries and depressed levels of consciousness or dysphagia. Careful attention to protein stores and electrolyte balance is critical during this phase of treatment.
Usually no general limitations are placed on activity. Patient-by-patient recommendations based on the individual's motoric and cognitive recovery are necessary.
Progesterone fails in traumatic brain injury. Melville NA. Medscape Medical News. December 11, 2014. [Full Text].
Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, et al. Very Early Administration of Progesterone for Acute Traumatic Brain Injury. N Engl J Med. 2014 Dec 10. [Medline].
Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, et al. A Clinical Trial of Progesterone for Severe Traumatic Brain Injury. N Engl J Med. 2014 Dec 10. [Medline].
Schwamm LH. Progesterone for Traumatic Brain Injury - Resisting the Sirens' Song. N Engl J Med. 2014 Dec 10. [Medline].
Wu AP, Davidson T. Posttraumatic anosmia secondary to central nervous system injury. Am J Rhinol. Nov-Dec/2008. 22:606-7.
Bhatoe HS. Primary brainstem injury: benign course and improved survival. Acta Neurochir (Wien). 1999. 141(5):515-9. [Medline].
Munjal SK, Panda NK, Pathak A. Dynamics of Hearing Status in Closed Head Injury. J Neurotrauma. Feb/2010. 27:309-316.
Mackay LE, Morgan AS, Bernstein BA. Factors affecting oral feeding with severe traumatic brain injury. J Head Trauma Rehabil. 1999 Oct. 14(5):435-47. [Medline].
Ellenberg JH, Levin HS, Saydjari C. Posttraumatic Amnesia as a predictor of outcome after severe closed head injury. Prospective assessment. Arch Neurol. 1996 Aug. 53(8):782-91. [Medline].
Crevits L, Hanse MC, Tummers P, et al. Antisaccades and remembered saccades in mild traumatic brain injury. J Neurol. 2000 Mar. 247(3):179-82. [Medline].
Tisdall M, Crocker M, Watkiss J, Smith M. Disturbances of sodium in critically ill adult neurologic patients: a clinical review. J Neurosurg Anesthesiol. 2006 Jan. 18(1):57-63. [Medline].
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. 2001 Jan. 70(1):95-100. [Medline].
Roberts I. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. 2000. CD000033. [Medline].
Stein SC. Minor head injury: 13 is an unlucky number. J Trauma. 2001 Apr. 50(4):759-60. [Medline].
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. 1997 May. 47(5):423-7. [Medline].
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. 1990 Nov. 73(5):688-98. [Medline].
Maxwell WL, MacKinnon MA, Smith DH, et al. Thalamic nuclei after human blunt head injury. J Neuropathol Exp Neurol. 2006 May. 65(5):478-88. [Medline].
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. 1995 Aug. 12(4):565-72. [Medline].
Jennett B, Adams JH, Murray LS, et al. Neuropathology in vegetative and severely disabled patients after head injury. Neurology. 2001 Feb 27. 56(4):486-90. [Medline].
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. 1992 Aug. 86(2):190-3. [Medline].
Bullock R, Zauner A, Woodward JJ, et al. Factors affecting excitatory amino acid release following severe human head injury. J Neurosurg. 1998 Oct. 89(4):507-18. [Medline].
DeGraba TJ, Pettigrew LC. Why do neuroprotective drugs work in animals but not humans?. Neurol Clin. 2000 May. 18(2):475-93. [Medline].
Jonas W, Lin Y, Tortella F. Neuroprotection from glutamate toxicity with ultra-low dose glutamate. Neuroreport. 2001 Feb 12,. 12(2):335-9. [Medline].
Yang SY, Gao ZX. Determination and clinical significance of plasma levels of prostaglandins in patients with acute brain injury. Surg Neurol. 1999 Sep. 52(3):238-45. [Medline].
Zubkov AY, Lewis AI, Raila FA, et al. Risk factors for the development of post-traumatic cerebral vasospasm. Surg Neurol. 2000 Feb. 53(2):126-30. [Medline].
Cox AL, Coles AJ, Nortje J, et al. An investigation of auto-reactivity after head injury. J Neuroimmunol. 2006 May. 174(1-2):180-6. [Medline].
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. 2007 Aug. 14(8):1529-41. [Medline].
Wang HE, Peitzman AB, Cassidy LD, et al. Out-of-hospital endotracheal intubation and outcome after traumatic brain injury. Ann Emerg Med. 2004 Nov. 44(5):439-50. [Medline].
Lannoo E, Van Rietvelde F, Colardyn F, et al. Early predictors of mortality and morbidity after severe closed head injury. J Neurotrauma. 2000 May. 17(5):403-14. [Medline].
Salim A, Hadjizacharia P, DuBose J, Brown C, Inaba K, Chan L. Role of anemia in traumatic brain injury. J Am Coll Surg. 2008 Sep. 207(3):398-406. [Medline].
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. 2008 Oct. 31(4):431-6; discussion 436-7. [Medline].
Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil. 2006 Nov-Dec. 21(6):544-8. [Medline].
Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry. 1996 Apr. 60(4):362-9. [Medline].
Wrightson P, Gronwall D. Mild head injury in New Zealand: incidence of injury and persisting symptoms. N Z Med J. 1998 Mar 27. 111(1062):99-101. [Medline].
Thurman D, Guerrero J. Trends in hospitalization associated with traumatic brain injury. JAMA. 1999 Sep 8. 282(10):954-7. [Medline].
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. 2004 Feb. (43 Suppl):28-60. [Medline].
Wagner AK, Sasser HC, Hammond FM, et al. Intentional traumatic brain injury: epidemiology, risk factors, and associations with injury severity and mortality. J Trauma. 2000 Sep. 49(3):404-10. [Medline].
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 Trauma Registry. J Trauma. 2007 May. 62(5):1259-62; discussion 1262-3. [Medline].
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. 2011 Nov. 39(11):2311-8. [Medline].
Bernal-Sprekelsen M, Bleda-Vazquez C, Carrau RL. Ascending meningitis secondary to traumatic cerebrospinal fluid leaks. Am J Rhinol. 2000 Jul-Aug. 14(4):257-9. [Medline].
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. 2006 Feb. 60(2):274-8. [Medline].
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.
Krauss JK, Trankle R, Kopp KH. Post-traumatic movement disorders in survivors of severe head injury. Neurology. 1996 Dec. 47(6):1488-92. [Medline].
Matser JT, Kessels AG, Jordan BD, et al. Chronic traumatic brain injury in professional soccer players. Neurology. 1998 Sep. 51(3):791-6. [Medline].
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. 1991 Aug. 75(2):256-61. [Medline].
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. 1999 Apr. 90(4):635-43. [Medline].
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. 1990 Apr. 53(4):293-6. [Medline].
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. 2000 May. 14(2):223-30. [Medline].
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].
Hefny AF, Eid HO, Abu-Zidan FM. Severe tyre blast injuries during servicing. Injury. 2009 May. 40(5):484-7. [Medline].
Bhattacharjee Y. Neuroscience. Shell shock revisited: solving the puzzle of blast trauma. Science. 2008 Jan 25. 319(5862):406-8. [Medline].
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. 2009 Jan. 15(1):1-8. [Medline].
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].
Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. Dec/2008. 65:1303-8.
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. 2008 Sep. 65(3):674-7. [Medline].
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.
Friedman G, Froom P, Sazbon L, et al. Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury. Neurology. 1999 Jan 15. 52(2):244-8. [Medline].
Kutner KC, Erlanger DM, Tsai J, et al. Lower cognitive performance of older football players possessing apolipoprotein E epsilon4. Neurosurgery. 2000 Sep. 47(3):651-7; discussion 657-8. [Medline].
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. 2008 Apr. 25(4):279-90. [Medline].
Jordan BD. Genetic influences on outcome following traumatic brain injury. Neurochem Res. 2007 Apr-May. 32(4-5):905-15. [Medline].
Bacic A, Gluncic I, Gluncic V. Disturbances in plasma sodium in patients with war head injuries. Mil Med. 1999 Mar. 164(3):214-7. [Medline].
Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma. 2000 Nov. 17(11):1029-39. [Medline].
Halpern CH, Reilly PM, Turtz AR, Stein SC. Traumatic coagulopathy: the effect of brain injury. J Neurotrauma. 2008 Aug. 25(8):997-1001. [Medline].
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. 2004 Sep. 18(9):899-909. [Medline].
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.
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. 2012 May 1. 78(18):1428-33. [Medline].
Haydel MJ, Preston CA, Mills TJ, et al. Indications for computed tomography in patients with minor head injury. N Engl J Med. 2000 Jul 13. 343(2):100-5. [Medline].
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. 2007 Mar 20. 146(6):397-405. [Medline].
Wang MC, Linnau KF, Tirschwell DL, Hollingworth W. Utility of repeat head computed tomography after blunt head trauma: a systematic review. J Trauma. 2006 Jul. 61(1):226-33. [Medline].
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. 2011 Jul. 29(6):656-64. [Medline].
Levin HS, Williams DH, Valastro M, et al. Corpus callosal atrophy following closed head injury: detection with magnetic resonance imaging. J Neurosurg. 1990 Jul. 73(1):77-81. [Medline].
Pierallini A, Pantano P, Fantozzi LM, et al. Correlation between MRI findings and long-term outcome in patients with severe brain trauma. Neuroradiology. 2000 Dec. 42(12):860-7. [Medline].
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. 2008 Mar. 29(3):514-9. [Medline].
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. 2008 May. 29(5):967-73. [Medline].
Fontaine A, Azouvi P, Remy P, et al. Functional anatomy of neuropsychological deficits after severe traumatic brain injury. Neurology. 1999 Dec 10. 53(9):1963-8. [Medline].
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. 2006 Feb. 27(2):447-51. [Medline].
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. 2000 Jul. 123 ( Pt 7):1403-9. [Medline].
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. 1999 Nov. 91(5):750-60. [Medline].
Steinbaugh LA, Lindsell CJ, Shutter LA, Szaflarski JP. Initial EEG predicts outcomes in a trial of levetiracetam vs. fosphenytoin for seizure prevention. Epilepsy Behav. 2012 Mar. 23(3):280-4. [Medline].
Carter BG, Butt W. Review of the use of somatosensory evoked potentials in the prediction of outcome after severe brain injury. Crit Care Med. 2001 Jan. 29(1):178-86. [Medline].
Hortobágyi 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. 2007 Apr. 33(2):226-37. [Medline].
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.
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.
White H, Cook D, Venkatesh B. The use of hypertonic saline for treating intracranial hypertension after traumatic brain injury. Anesth Analg. 2006 Jun. 102(6):1836-46. [Medline].
Shafi S, Diaz-Arrastia R, Madden C, Gentilello L. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma. 2008 Feb. 64(2):335-40. [Medline].
Farahvar A, Gerber LM, Chiu YL, Carney N, Härtl R, Ghajar J. Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring. J Neurosurg. 2012 Aug 17. [Medline].
Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: management protocol and clinical results. J Neurosurg. 1995 Dec. 83(6):949-62. [Medline].
White H, Venkatesh B. Cerebral perfusion pressure in neurotrauma: a review. Anesth Analg. Sep/2008. 107:979-88.
The SAFE Study Investigators. Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury. NEJM. Aug/2007. 357:874-84.
Clifton GL, Miller ER, Choi SC, et al. Lack of effect of induction of hypothermia after acute brain injury. N Engl J Med. 2001 Feb 22. 344(8):556-63. [Medline].
Sydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev. Apr/2009. 15:CD001048.
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. 2011 Feb. 10(2):131-9. [Medline].
Härtl R, Gerber LM, Ni Q, Ghajar J. Effect of early nutrition on deaths due to severe traumatic brain injury. J Neurosurg. 2008 Jul. 109(1):50-6. [Medline].
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.
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.
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. 2004 Oct 9. 364(9442):1321-8. [Medline].
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. 1990 Aug 23. 323(8):497-502. [Medline].
Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg. 1999 Oct. 91(4):593-600. [Medline].
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].
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. 2007 Jan. 6(1):29-38. [Medline].
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. 2007 Apr. 49(4):391-402, 402.e1-2. [Medline].
Empey PE, McNamara PJ, Young B, et al. Cyclosporin A disposition following acute traumatic brain injury. J Neurotrauma. 2006 Jan. 23(1):109-16. [Medline].
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. 2006 Jan. 5(1):38-45. [Medline].
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. 2008 Aug. 25(8):1011-7. [Medline].
Sullivan PG, Geiger JD, Mattson MP, et al. Dietary supplement creatine protects against traumatic brain injury. Ann Neurol. 2000 Nov. 48(5):723-9. [Medline].
Cirak B, Rousan N, Kocak A, et al. Melatonin as a free radical scavenger in experimental head trauma. Pediatr Neurosurg. 1999 Dec. 31(6):298-301. [Medline].
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. 1999 Jan. 80(1):13-9. [Medline].
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. 2000 Oct. 69(4):499-506. [Medline].
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. 1996 Jun. 77(6):536-40. [Medline].
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. 2006 Jan. 20(1):24-30. [Medline].
Zhang L, Plotkin RC, Wang G, et al. Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil. 2004 Jul. 85(7):1050-5. [Medline].
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].
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. 2000 Mar. 15(2):313-7. [Medline].
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. 1999 Jan. 13(1):63-8. [Medline].
Nahas Z, Arlinghaus KA, Kotrla KJ, et al. Rapid response of emotional incontinence to selective serotonin reuptake inhibitors. J Neuropsychiatry Clin Neurosci. 1998 Fall. 10(4):453-5. [Medline].
Fann JR, Uomoto JM, Katon WJ. Sertraline in the treatment of major depression following mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2000 Spring. 12(2):226-32. [Medline].
Page S, Levine Peter. Forced use after TBI: promoting plasticity and function through practice. Brain Inj. 2003 Aug. 17(8):675-84. [Medline].
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. 2000 Jun 21. 283(23):3075-81. [Medline].
Zhao H, Bai XJ. Influence of operative timing on prognosis of patients with acute subdural hematoma. Chin J Traumatol. Oct/2009. 12:296-8.
Croce MA, Dent DL, Menke PG, et al. Acute subdural hematoma: nonsurgical management of selected patients. J Trauma. 1994 Jun. 36(6):820-6; discussion 826-7. [Medline].
Patel NY, Hoyt DB, Nakaji P, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma. Mar/2000. 48:367-74.
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. 2008 Aug. 65(2):380-5; discussion 385-6. [Medline].
Holder HD, Gruenewald PJ, Ponicki WR, et al. Effect of community-based interventions on high-risk drinking and alcohol-related injuries. JAMA. 2000 Nov 8. 284(18):2341-7. [Medline].
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. 1999 Oct. 230(4):473-80; discussion 480-3. [Medline].
Thompson DC, Rivara FP, Thompson R. Helmets for preventing head and facial injuries in bicyclists. Cochrane Database Syst Rev. 2000. CD001855. [Medline].
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. 2006 May. 47(5):367-72. [Medline].
Lee BH, Schofer JL, Koppelman FS. Bicycle safety helmet legislation and bicycle-related non-fatal injuries in California. Accid Anal Prev. 2005 Jan. 37(1):93-102. [Medline].
Donders J, Boonstra T. Correlates of invalid neuropsychological test performance after traumatic brain injury. Brain Inj. 2007 Mar. 21(3):319-26. [Medline].
Hutchison M, Comper P, Mainwaring L, Richards D. The influence of musculoskeletal injury on cognition: implications for concussion research. Am J Sports Med. 2011 Nov. 39(11):2331-7. [Medline].
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. 1986 Aug. 65(2):203-10. [Medline].
Deb S, Lyons I, Koutzoukis C. Neuropsychiatric sequelae one year after a minor head injury. J Neurol Neurosurg Psychiatry. 1998 Dec. 65(6):899-902. [Medline].
Dikmen SS, Corrigan JD, Levin HS, et al. Cognitive Outcome Following Traumatic Brain Injury. J Head Trauma Rehabil. 2009. 24:430-438.
Cantu RC. Second-impact syndrome. Clin Sports Med. 1998 Jan. 17(1):37-44. [Medline].
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.
McCrory PR, Berkovic SF. Second impact syndrome. Neurology. 1998 Mar. 50(3):677-83. [Medline].
Mayers L. Return-to-Play Criteria After Athletic Concussion. Arch Neurol. Sept/2008. 65:1158-1161.
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. 1999 May. 40(5):584-9. [Medline].
Angeleri F, Majkowski J, Cacchio G, et al. Posttraumatic epilepsy risk factors: one-year prospective study after head injury. Epilepsia. 1999 Sep. 40(9):1222-30. [Medline].
Diaz-Arrastia R, Agostini MA, Frol AB, et al. Neurophysiologic and neuroradiologic features of intractable epilepsy after traumatic brain injury in adults. Arch Neurol. 2000 Nov. 57(11):1611-6. [Medline].
Obermann M, Holbe D, Katsarava Z. Post-traumatic headache. Expert Rev Neurother. Sep/2009. 9:1361-1370.
Packard RC, Ham LP. Pathogenesis of posttraumatic headache and migraine: a common headache pathway?. Headache. 1997 Mar. 37(3):142-52. [Medline].
Warner JS. Posttraumatic headache--a myth?. Arch Neurol. 2000 Dec. 57(12):1778-80; discussion 1780-1. [Medline].
Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following traumatic brain injury. Arch Gen Psychiatry. 2004 Jan. 61(1):42-50. [Medline].
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. 2004 Jun. 17(2):118-20. [Medline].
Sachdev P, Smith JS, Cathcart S. Schizophrenia-like psychosis following traumatic brain injury: a chart- based descriptive and case-control study. Psychol Med. 2001 Feb. 31(2):231-9. [Medline].
McCartan DP, Fleming FJ, Motherway C, Grace PA. Management and outcome in patients following head injury admitted to an Irish Regional Hospital. Brain Inj. 2008 Apr. 22(4):305-12. [Medline].
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. 1999 Feb. 66(2):207-13. [Medline].
Chamelian L, Feinstein A. Outcome after mild to moderate traumatic brain injury: the role of dizziness. Arch Phys Med Rehabil. 2004 Oct. 85(10):1662-6. [Medline].
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. 2011 Feb 17. [Medline].
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. 2000 Jul. 7(4):301-4. [Medline].
Wade DT, King NS, Wenden FJ, et al. Routine follow up after head injury: a second randomised controlled trial. J Neurol Neurosurg Psychiatry. 1998 Aug. 65(2):177-83. [Medline].
Schanke AK, Sundet K. Comprehensive driving assessment: neuropsychological testing and on- road evaluation of brain injured patients. Scand J Psychol. 2000 Jun. 41(2):113-21. [Medline].
Anderson P. Hemodynamic Complications Common in Traumatic Brain Injury. Available at http://www.medscape.com/viewarticle/778999. Accessed: March 25, 2013.
Bazarian JJ, McClung J, Shah MN, et al. Mild traumatic brain injury in the United States, 1998--2000. Brain Inj. 2005 Feb. 19(2):85-91. [Medline].
Black K, Zafonte R, Millis S, et al. Sitting balance following brain injury: does it predict outcome?. Brain Inj. 2000 Feb. 14(2):141-52. [Medline].
Blumbergs PC, Scott G, Manavis J, et al. Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet. 1994 Oct 15. 344(8929):1055-6. [Medline].
Bruce DA, Alavi A, Bilaniuk L, et al. Diffuse cerebral swelling following head injuries in children: the syndrome of "malignant brain edema". J Neurosurg. 1981 Feb. 54(2):170-8. [Medline].
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. 2000 Apr 20. 342(16):1179-86. [Medline].
Centers for Disease Control and Prevention. Sports-related recurrent brain injuries--United States. MMWR Morb Mortal Wkly Rep. 1997 Mar 14. 46(10):224-7. [Medline].
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. 2000 Jan. 17(1):53-68. [Medline].
Chesnut RM. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma. Aug/2008. 65:500-1.
Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma. 1993 Feb. 34(2):216-22. [Medline].
Chiu WT, Kuo CY, Hung CC, et al. The effect of the Taiwan motorcycle helmet use law on head injuries. Am J Public Health. 2000 May. 90(5):793-6. [Medline].
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].
Collins MW, Grindel SH, Lovell MR, et al. Relationship between concussion and neuropsychological performance in college football players. JAMA. 1999 Sep 8. 282(10):964-70. [Medline].
Dharap SB, Khandkar AA, Pandey A, Sharma AK. Repeat CT scan in closed head injury. Injury. 2005 Mar. 36(3):412-6. [Medline].
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. 2000 Oct. 15(5):1103-12. [Medline].
Eisenberg HM, Frankowski RF, Contant CF, et al. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988 Jul. 69(1):15-23. [Medline].
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.
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. 1996 Jul. 85(1):131-7. [Medline].
Gordon WA, Brown M, Sliwinski M, et al. The enigma of "hidden" traumatic brain injury. J Head Trauma Rehabil. 1998 Dec. 13(6):39-56. [Medline].
Guerra WK, Gaab MR, Dietz H, et al. Surgical decompression for traumatic brain swelling: indications and results. J Neurosurg. 1999 Feb. 90(2):187-96. [Medline].
Gusmao SN, Pittella JE. Extradural haematoma and diffuse axonal injury in victims of fatal road traffic accidents. Br J Neurosurg. 1998 Apr. 12(2):123-6. [Medline].
Haig AJ, Ruess JM. Recovery from vegetative state of six months'' duration associated with Sinemet (levodopa/carbidopa). Arch Phys Med Rehabil. 1990 Dec. 71(13):1081-3. [Medline].
Hall JR, Reyes HM, Horvat M, et al. The mortality of childhood falls. J Trauma. 1989 Sep. 29(9):1273-5. [Medline].
Haltiner AM, Newell DW, Temkin NR, et al. Side effects and mortality associated with use of phenytoin for early posttraumatic seizure prophylaxis. J Neurosurg. 1999 Oct. 91(4):588-92. [Medline].
Hamill RW, Woolf PD, McDonald JV, et al. Catecholamines predict outcome in traumatic brain injury. Ann Neurol. 1987 May. 21(5):438-43. [Medline].
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. 1999 Nov. 13(11):873-87. [Medline].
Harders A, Kakarieka A, Braakman R. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. J Neurosurg. 1996 Jul. 85(1):82-9. [Medline].
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. 2000 Feb. 25(2):269-76. [Medline].
Ikonomidou C, Stefovska V, Turski L. Neuronal death enhanced by N-methyl-D-aspartate antagonists. Proc Natl Acad Sci U S A. 2000 Nov 7. 97(23):12885-90. [Medline].
Inamasu J, Hori S, Aoki K, et al. CT scans essential after posttraumatic loss of consciousness. Am J Emerg Med. 2000 Nov. 18(7):810-1. [Medline].
Jordan BD, Relkin NR, Ravdin LD, et al. Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing. JAMA. 1997 Jul 9. 278(2):136-40. [Medline].
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. 1999 Jan. 134(1):14-7. [Medline].
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. 2002 Mar. 30(3):548-54. [Medline].
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. 2002 Aug 15. 104(2):148-58. [Medline].
Kobrine AI, Timmins E, Rajjoub RK, et al. Demonstration of massive traumatic brain swelling within 20 minutes after injury. Case report. J Neurosurg. 1977 Feb. 46(2):256-8. [Medline].
Lal S, Merbtiz CP, Grip JC. Modification of function in head-injured patients with Sinemet. Brain Inj. 1988 Jul-Sep. 2(3):225-33. [Medline].
Landau WM. Tizanidine and spasticity. Neurology. 1995 Dec. 45(12):2295-6. [Medline].
Landy PJ. Neurological sequelae of minor head and neck injuries. Injury. 1998 Apr. 29(3):199-206. [Medline].
Lane PL, Skoretz TG, Doig G, et al. Intracranial pressure monitoring and outcomes after traumatic brain injury. Can J Surg. 2000 Dec. 43(6):442-8. [Medline].
Lang DA, Teasdale GM, Macpherson P, et al. Diffuse brain swelling after head injury: more often malignant in adults than children?. J Neurosurg. 1994 Apr. 80(4):675-80. [Medline].
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. 1990 Nov. 73(5):699-709. [Medline].
Levin HS, Mattis S, Ruff RM, et al. Neurobehavioral outcome following minor head injury: a three-center study. J Neurosurg. 1987 Feb. 66(2):234-43. [Medline].
Levin HS, Williams DH, Eisenberg HM, et al. Serial MRI and neurobehavioural findings after mild to moderate closed head injury. J Neurol Neurosurg Psychiatry. 1992 Apr. 55(4):255-62. [Medline].
Li J, Brown J, Levine M. Mild head injury, anticoagulants, and risk of intracranial injury. Lancet. 2001 Mar 10. 357(9258):771-2. [Medline].
Macfarlane DP, Nicoll JA, Smith C, et al. APOE epsilon4 allele and amyloid beta-protein deposition in long term survivors of head injury. Neuroreport. 1999 Dec 16. 10(18):3945-8. [Medline].
Marion DW, Penrod LE, Kelsey SF, et al. Treatment of traumatic brain injury with moderate hypothermia. N Engl J Med. 1997 Feb 20. 336(8):540-6. [Medline].
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.
Marshall LF, Gautille T, Klauber MR, et al. The outcome of severe head injury. J Neurosurg. 1991. 75:S28-36.
Mayers l. Return-to-Play Criteria after Athletic Concussion. Archives of Neurology. Sep/2008. 65:1158-1161.
Miller EC, Derlet RW, Kinser D. Minor head trauma: Is computed tomography always necessary?. Ann Emerg Med. 1996 Mar. 27(3):290-4. [Medline].
Mittenberg W, Strauman S. Diagnosis of mild head injury and the postconcussion syndrome. J Head Trauma Rehabil. 2000 Apr. 15(2):783-91. [Medline].
Mosimann UP, Muri RM, Felblinger J, et al. Saccadic eye movement disturbances in whiplash patients with persistent complaints. Brain. 2000 Apr. 123 ( Pt 4):828-35. [Medline].
Murray JA, Demetriades D, Berne TV, et al. Prehospital intubation in patients with severe head injury. J Trauma. 2000 Dec. 49(6):1065-70. [Medline].
Nagy KK, Joseph KT, Krosner SM, et al. The utility of head computed tomography after minimal head injury. J Trauma. 1999 Feb. 46(2):268-70. [Medline].
Owings JT, Wisner DH, Battistella FD, et al. Isolated transient loss of consciousness is an indicator of significant injury. Arch Surg. 1998 Sep. 133(9):941-6. [Medline].
Packard RC, Ham LP. Posttraumatic headache. J Neuropsychiatry Clin Neurosci. 1994 Summer. 6(3):229-36. [Medline].
Palmer AM, Marion DW, Botscheller ML, et al. Traumatic brain injury-induced excitotoxicity assessed in a controlled cortical impact model. J Neurochem. 1993 Dec. 61(6):2015-24. [Medline].
Patel NY, Hoyt DB, Nakaji P, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma. 2000 Mar. 48(3):367-74; discussion 374-5. [Medline].
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. 2000 Dec. 49(6):1071-5. [Medline].
Pop E. Dexanabinol Pharmos. Curr Opin Investig Drugs. 2000 Dec. 1(4):494-503. [Medline].
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. 2000 Mar. 44(1):11-8. [Medline].
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. 1997 Mar. 48(3):581-5. [Medline].
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. 2001 Apr. 70(4):530-3. [Medline].
Salmond CH, Menon DK, Chatfield DA, et al. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage. 2006 Jan 1. 29(1):117-24. [Medline].
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. 2004 Sep. 21(9):1154-67. [Medline].
Sloan RL, Brown KW, Pentland B. Fluoxetine as a treatment for emotional lability after brain injury. Brain Inj. 1992 Jul-Aug. 6(4):315-9. [Medline].
Snoek JW, Minderhoud JM, Wilmink JT. Delayed deterioration following mild head injury in children. Brain. 1984 Mar. 107 ( Pt 1):15-36. [Medline].
Speech TJ, Rao SM, Osmon DC, et al. A double-blind controlled study of methylphenidate treatment in closed head injury. Brain Inj. 1993 Jul-Aug. 7(4):333-8. [Medline].
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. 2001 Feb. 18(2):115-25. [Medline].
Sturmi JE, Smith C, Lombardo JA. Mild brain trauma in sports. Diagnosis and treatment guidelines. Sports Med. 1998 Jun. 25(6):351-8. [Medline].
Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE. Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death?. J Neurosci Res. 2005 Jan 1-15. 79(1-2):231-9. [Medline].
Teasdale GM. Head injury. J Neurol Neurosurg Psychiatry. 1995 May. 58(5):526-39. [Medline].
The Brain Trauma Foundation, The American Association of Neurological Surgeons, The Joint Section on Neurotrauma and Critical Care. Role of steroids. J Neurotrauma. 2000 Jun-Jul. 17(6-7):531-5. [Medline].
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. 2000 Jun-Jul. 17(6-7):527-30. [Medline].
Thurman DJ, Alverson C, Dunn KA, et al. Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehabil. 1999 Dec. 14(6):602-15. [Medline].
Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000 Jan 25. 54(2):340-5. [Medline].
van Reekum R, Cohen T, Wong J. Can traumatic brain injury cause psychiatric disorders?. J Neuropsychiatry Clin Neurosci. 2000 Summer. 12(3):316-27. [Medline].
Velmahos GC, Jindal A, Chan LS, et al. "Insignificant" mechanism of injury: not to be taken lightly. J Am Coll Surg. 2001 Feb. 192(2):147-52. [Medline].
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. 2000 May. 35(5):688-9. [Medline].
Whelan FJ, Walker MS, Schultz SK. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. 2000 Sep. 12(3):131-5. [Medline].
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. 1997 Nov-Dec. 76(6):440-50. [Medline].
Wilberger JE Jr, Harris M, Diamond DL. Acute subdural hematoma: morbidity, mortality, and operative timing. J Neurosurg. 1991 Feb. 74(2):212-8. [Medline].
Withaar FK, Brouwer WH, van Zomeren AH. Fitness to drive in older drivers with cognitive impairment. J Int Neuropsychol Soc. 2000 May. 6(4):480-90. [Medline].
Young B, Runge JW, Waxman KS, et al. Effects of pegorgotein on neurologic outcome of patients with severe head injury. A multicenter, randomized controlled trial. JAMA. 1996 Aug 21. 276(7):538-43. [Medline].
Zafonte RD, Mann NR. Cerebral salt wasting syndrome in brain injury patients: a potential cause of hyponatremia. Arch Phys Med Rehabil. 1997 May. 78(5):540-2. [Medline].