AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 most commonly is classified by the initial postresuscitation Glasgow Coma Scale (GCS) score, which generates a numerical summed score for eye, motor, and verbal abilities. 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. Concussion and mild head injury are synonymous.

Research on head injury has advanced considerably in the past 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, 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.

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 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.

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.

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. More severe and diffuse axonal injury has been found to correlate with vegetative states and the acute onset of coma following injury.

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). 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.

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. 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.

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. 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.

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.

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 mice, transthyretin mRNA levels increase for 2 hours to 2 weeks following a concussive impact. This protein binds amyloid protein and may offer neuroprotection after head injury.

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.

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 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.

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 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 during the period 1974-1976. Using a door-to-door survey methodology, researchers have estimated that 56 cases per 100,000 persons per year in China sustained a brain injury in 1983.

Head injury data are difficult to compare internationally for various reasons, including inconsistencies and complexities of diagnostic coding and inclusion criteria, transfers to multiple care facilities (ie, 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.

Mortality/Morbidity

In the United States each year, 50,000 individuals die from head injuries, and almost twice that number suffer permanent disability.

Race

An older study from the Chicago region documented that black residents experienced twice the risk of head injury as white residents. A more recent 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. Furthermore, a study of moderate and severe head injury in 106 children reported that African Americans had worse functional outcomes 1 year after head injury than their white counterparts. This puzzling relationship existed even after considering the socioeconomic and educational levels of the parents.

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.

Age

Approximately half of the patients admitted to a hospital for head injury are aged 24 years or younger.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

History in most patients with head injury should be self-evident. However, consider trauma with intracerebral pathology in any patient with a coma of unknown etiology.

• In the acute setting, the patient may be comatose or confused, and witnesses to the accident or injury are of obvious and crucial importance.
• Elicit the type and mechanisms of the injury, as these may have prognostic value. Patients sustaining a head injury from an assault or from being struck with a falling object have a markedly greater likelihood of poorer vocational outcomes than patients sustaining the more common acceleration/deceleration injuries, presumably because the former injury types entail greater axonal damage.
• Ascertain whether the patient lost consciousness. Even a questionable loss of consciousness can be a marker of severe neurological injury.
• The presence of prior head injuries, particularly prior concussive episodes in sports, can indicate the potential for more severe long-term outcomes.
• Remote or active drug or alcohol use may raise the risk of intracranial bleeding and cloud the mental status assessment.
• Present anticoagulant therapy is also worrisome.
• Carefully consider past psychiatric disease and a premorbid history of headaches.

Physical

• Elemental neurologic examination
• • The GCS is the mainstay for rapid neurologic assessment in acute head injury. Both initial and worst GCS postresuscitation scores have correlated significantly with 1-year outcomes following severe head injury.
  • Following ascertainment of the GCS score, focus the examination on signs of external trauma. Bruising or bleeding on the head and scalp and blood in the ear canal or behind the tympanic membranes may be clues to occult brain injuries. Also consider coexistent cervical spine and other systemic injuries.
  • Anosmia is common and probably is caused by the shearing of the olfactory nerves at the cribriform plate. If accompanied by rhinorrhea, a CSF leak with the attendant risk of ascending meningitis must be excluded.
  • Abnormal postresuscitation pupillary reactivity correlates with a poor 1-year outcome. In fact, a 2006 study reported no survivors among 173 head-injured patients who presented with bilaterally fixed and dilated pupils and a GCS score of 3. A unilaterally dilated pupil with or without ipsilateral cranial nerve (CN) III paralysis may indicate impending herniation.
  • Isolated internuclear ophthalmoplegia secondary to traumatic brainstem injuries has been described and has a relatively benign prognosis.
  • CN VI palsies may indicate raised intracranial pressure. CN VII palsy, particularly in association with decreased hearing, may indicate a fracture of the temporal bone.
  • Dysphagia raises the risk of both aspiration and inadequate nutrition.
  • Focal motor findings may be manifestations of a localized contusion or, more ominously, an early herniation syndrome.
    • Flexor or extensor posturing obviously implies extensive intracranial pathology or raised intracranial pressure. In the chronic phase, motoric manifestations typically include spasticity or, more unusually, akinesia and rigidity.
    • Tremors and dystonia recede with time, but these still can affect as many as 12% of survivors of severe head injury 2 years after the initial trauma.
    • Although postural stability and balance depend on inputs from multiple components of the nervous system, impairments in sitting balance alone have been demonstrated to be predictive of poor functional abilities upon discharge from rehabilitation.
    • Primitive reflexes, despite their presence in some healthy elderly patients, are useful and when multiple can correlate with cognitive deficits.
• Bedside cognitive testing
• • In the acute setting, measurements of the patient's level of consciousness, attention, and orientation are of primary importance. Aphasia obviously implicates localized pathology.
  • Lucid intervals are not unusual. Of 838 patients with severe head injury in one study, 25% talked at some point between the trauma onset and their deterioration into coma. Although 81% of these patients had a focal lesion, 19% exhibited diffuse brain swelling, and approximately one third of these patients demonstrated coexistent subarachnoid hemorrhage or other nonfocal intracranial bleeding. Such diffuse swelling was much more likely in children and adolescents than adults.
  • Some patients acutely recovering from head trauma demonstrate no ability to retain new information.
    • This inability to lay down new memories after a head injury originally was labeled posttraumatic amnesia.
    • The patient's subjective estimate of his or her first recollection of events following the head injury defined the termination of this period.
    • These subjective estimates have yielded in recent years to prospective serial mental status assessments. These mental status assessments have validated the prognostic value of the duration of posttraumatic amnesia; patients with longer durations of posttraumatic amnesia have poorer outcomes.
    • Furthermore, more recent work has suggested that posttraumatic amnesia is somewhat of a misnomer. Because severe inattention in the postinjury state primarily prevents retention of new information, "posttraumatic confusional state" is a more accurate descriptor.
  • In the long-term setting, bedside cognitive tests are employed to help distinguish damaged and spared realms of cognitive functioning.
    • Even though most of these tests are not quantitative, they readily provide the examiner with immediate information to help in diagnosis and therapy.
    • One standardized test that can be administered easily is the Mini-Mental State Examination. Although this test disproportionately emphasizes left hemisphere functioning, one study has documented that 23% of patients with mild head injuries score less than 24 out of 30 points when assessed with this instrument 1 year after injury.
  • Although all cognitive domains should be assessed, the investigation of frontal or executive systems assumes even greater importance in the long-term setting. While examining mnemonic and visual spatial and language functioning, the quality of the patient's responses, whether perseverative or impulsive, socially sanctioned or grossly inappropriate, is also important to observe and document.
  • Motor regulation can be assessed rapidly using the Luria "fist, chop, slap" sequencing task.
  • An antisaccade task, in which the patient looks away from the offered visual stimulus, recently has been shown to be impaired in patients with symptomatic whiplash injury compared to controls, although the sensitivity of this test in detecting brain injury has been questioned.
  • Letter fluency, in which the patient names as many words as possible beginning with a specific letter in 1 minute, and category fluency, in which the patient names as many items as possible in a certain category in 1 minute, provide further information about self-generative frontal processes.
  • An untimed Trails B test, in which the patient alternates between number and letter sequences, allows further qualitative testing of frontal functioning. Be cautious in overinterpreting this or any single test. Malingerers have been shown to fake performance errors on the Trails B.

Causes

• Road accidents involving motor vehicle drivers and occupants, cyclists, and pedestrians are the main risk factor for head injuries.
• Assaults in economically depressed regions and during wartime are other major risk factors.
• Athletic participation, especially football and soccer, is another important cause of these injuries.
• Falls cause head injuries in elderly patients and children, occasionally with catastrophic results.
• Anticoagulants and antiplatelet medications, such as aspirin, raise the risk of intracranial bleeding with even trivial head injuries.
• Alcohol use raises the risks of incurring a head injury.
• • Perhaps because it may impede excitotoxicity, alcohol use at the time of injury may decrease the likelihood of a poor outcome.
  • A newer study of intentional head injuries reported that patients consuming alcohol had higher initial GCS scores. Another study of patients with apparently trivial injuries (patients either were found down or fell from heights <10 ft) found that outcomes were better in patients who were severely intoxicated (blood alcohol levels >200 mg/dL).
• Although the presence of APOE4 alleles is not an established risk factor for head injury, the presence of even one of these alleles increases the risk of a poor outcome.
• • Patients who are homozygous or heterozygous for the APOE4 allele have an almost 14-times greater likelihood of a poor outcome after head injury than those with other APOE genotypes.
  • Similarly, football players and boxers with an APOE4 allele are at greater risk for posttraumatic cognitive problems than APOE4-negative athletes.
  • Other genetic determinants of head injury undoubtedly will surface with further research.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Alterations in serum sodium levels are critical and occur in as many as 50% of comatose patients with head injuries.
• • Hyponatremia may be due to the syndrome of inappropriate antidiuretic hormone (SIADH) or cerebral salt wasting. Both syndromes involve decreased serum sodium level in the face of increased urinary sodium losses.
  • Unlike SIADH, in which the patient is euvolemic, cerebral salt wasting typically occurs with volume depletion and is caused by the release of a natriuretic hormone. Some researchers suggest that this natriuretic hormone can be measured readily in the serum because it binds to digoxin antibodies and produces a false-positive test for digoxin in patients who are not receiving this medication.
  • Elevated sodium levels in head injury indicate simple dehydration or diabetes insipidus.
• Magnesium is depleted in the acute phases of both minor and severe head injuries.
• • Because this cation blocks the excitotoxic response and functions as an antioxidant, careful monitoring of magnesium may improve outcomes.
  • Early administration of magnesium has attenuated experimental brain injury in rats.
• Coagulation studies, including prothrombin times (PT), activated partial thromboplastin times (aPTT), and platelet counts, are important to exclude a coagulopathy.
• Blood alcohol levels and drug screens are important because positive results may help explain subnormal levels of consciousness and cognition in some patients with head trauma.
• Obtain renal function tests and creatine kinase levels to help exclude rhabdomyolysis if a crush injury has occurred or marked rigidity is present.
• Elevated serum levels of neuron-specific enolase and protein S-100 B obtained within 24 hours of head injury have been demonstrated to correlate with persistent cognitive impairment at 6 months in patients with severe or mild head injuries. Neuron-specific enolase and S-100 B elevations have been correlated with frequent "headings" of balls during soccer playing. Although further research is needed, the ease of measuring these serum proteins makes them potential prognostic biomarkers.

Imaging Studies

• Computerized tomography (CT) is the main imaging modality employed in the acute setting. Magnetic resonance imaging (MRI) typically is reserved for patients who have mental status abnormalities unexplained by CT scan findings.
• • Controversy exists as to whether all patients with mild head injuries should have neuroimaging. In general, patients with any loss of consciousness should undergo CT scanning.
  • Some researchers have established clinical criteria to identify those patients who are most likely to have abnormal scans. For example, in a group of 909 consecutive patients who had experienced a mild head injury with a transient loss of consciousness, yet scored a full 15 on their initial GCS, all 57 (6%) patients with abnormal CT scans were identified by the presence of any one of the following clinical features: age older than 60 years, headaches, vomiting, alcohol or drug intoxication, trauma above the clavicles, memory problems, or seizures. Further validation of such imaging rules is needed.
  • Repeat CT is needed, of course, when clinical deterioration occurs. The need for routine repeat head CT is unclear. A 2006 multistudy review found neurosurgical interventions resulting from a repeat CT scan occurred in 0-54% of patients.
• MRI has been demonstrated to be more sensitive than CT scanning, particularly at identifying nonhemorrhagic diffuse axonal injury lesions.
• • MRI imaging has shown degeneration of the corpus callosum following severe head injuries with axonal damage in adults and children.
  • Specialized MRI techniques have demonstrated that deep lesions (lesions in the thalamus, cerebellum, and brain stem) in children with head injuries correlate with poor 1-year functional outcomes.
  • Furthermore, increased total lesion volume on fluid-attenuated inversion-recovery (FLAIR) MRI images has been demonstrated to correlate with poor clinical outcomes as well.
• Diffusion-weighted imaging may disclose abnormal lesions in patients with head injury even when their conventional MRI scans are unremarkable. Remember that white matter hyperintensities in patients with head trauma may recede when initial MRI scans are compared with those obtained in the months following the injury. A current study of 16 patients with mild-to-severe head injuries who underwent diffusion tensor imaging 6 months after their ictus displayed diffuse abnormalities that correlated with impairments in learning and memory.
• Functional imaging and MRI spectroscopy may have eventual clinical utility. At present, they are promising research tools.
• • Behavioral disorders, memory, and executive dysfunction correlated with abnormalities of cingulate gyrus metabolism in 13 patients with severe head injuries who underwent resting 18F-fluorodeoxyglucose positron emission tomographic (PET) imaging and a battery of neuropsychological tests. A more recent study found that while only 34% of CT results were abnormal in 92 patients with mild head injury, 63% of SPECT results demonstrated regions of hypoperfusion within 72 hours of the trauma. Frontal hypoperfusion predominated in adults.
  • Proton magnetic resonance spectroscopy of frontal white matter that appears normal on MRI has shown an increase in the choline-creatine ratio in patients with mild head injuries indicating aberrant metabolism.

Other Tests

• EEG is of limited usefulness in patients with head injuries.
• • Although certain EEG patterns may have prognostic significance, considerable interpretation is needed, and sedative medications and electrical artifacts are confounding.
  • The most useful role of EEG in head injuries may be to assist in the diagnosis of nonconvulsive status epilepticus. In a recent study that used both clinical and EEG criteria, nonconvulsive status epilepticus was diagnosed in 8% of 236 comatose patients. Although identification of nonconvulsive status epilepticus in a comatose patient may imply improved outcome with treatment of the seizures, the patients identified in nonconvulsive status in this study did not have improved outcomes compared with those patients who were not in nonconvulsive status.
  • A recent meta-analysis of the prognostic ability of somatosensory evoked potentials in predicting outcomes in patients with severe brain injuries examined 44 studies and found that if patients with focal lesions, recent decompressive craniotomies, or subdural and extradural fluid collections were excluded, bilaterally absent somatosensory evoked potentials correctly predicted unfavorable outcomes in 99.5% of patients.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Acute management
• • 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. The mere insertion of an intracranial pressure monitor has been associated with improved survival. 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.)
  • 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.
  • 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, in a post hoc analysis, this study found that the rewarming of patients with head injury who arrived in the emergency department already hypothermic was likely detrimental.
  • Steroids have demonstrated no benefits 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 one 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 humans 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 two large trials of patients with all types of traumatic intracranial injuries.
  • Although numerous synthetic neuroprotective agents are under development, several existing substances also show promise.
    • Because of its excitotoxic blocking properties, magnesium chloride has been used to reduce cortical injury in experimentally brain-injured rats.
    • Melatonin is a free radical scavenger, and when injected early in brain-injured rats, it significantly reduced levels of lipid breakdown products.
    • 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.
    • 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.
    • 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.
• Long-term management
• • 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 are used and demonstrable functional improvement has been lacking.
    • 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 cognitive rehabilitation than those in the control group.

Surgical Care

Two decades ago, the prompt surgical evacuation of subdural hematomas in less than 4 hours was believed to be a major determinant of an optimal outcome. Subsequent studies have found that the extent of the original intracranial injury and the generated intracranial pressures are 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 especially prone to nonoperative failures.
• Some have advocated surgical decompressive craniectomies for patients with increased intracranial pressure refractory to conventional medical treatment. Of 57 patients with head injuries undergoing this procedure, 58% reportedly attained a good outcome.
• 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.

Consultations

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.

Diet

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.

Activity

Usually no general limitations are placed on activity. Patient-by-patient recommendations based on the individual's motoric and cognitive recovery are necessary.

MEDICATION

Section 7 of 11  

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• Differentials
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medications commonly are used in the acute setting to control early seizures, reduce intracranial pressure, and correct electrolyte abnormalities. Nimodipine may be neuroprotective in the subset of patients with traumatic subarachnoid hemorrhages.

In the long-term setting, cognitive and motoric augmentation as well as the control of spasticity and emotional incontinence may require pharmacologic interventions.

Drug Category: Osmotic diuretics

These agents may help reduce intracranial pressure.

Drug Category: Anticonvulsants

These agents may help prevent early seizures in head injury.

Drug Category: Electrolytes

Magnesium is given in hypomagnesemic states to ensure that adequate stores are present during acute phase of head injuries.

Drug Category: Barbiturates

These agents may help reduce intracranial pressure that is refractory to other conventional measures.

Drug Category: Calcium channel blocker

Nimodipine has been demonstrated to improve outcomes of patients with traumatic subarachnoid hemorrhages.

Drug Category: Stimulants

These agents may help increase alertness and some aspects of cognitive functioning in patients with brain injury.

Drug Category: Dopamine agonist

These agents may increase alertness in patients with brain injury; also may help in occasional patients with posttraumatic parkinsonism.

Drug Category: Selective serotonin reuptake inhibitors

These agents have been of benefit in patients with head injuries and emotional incontinence.

Drug Category: Antispasticity medications

These agents may reduce painful cramping and detrimental muscle tightening.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• This needs to be individualized. Certainly after a moderate or severe head injury, transfer to an inpatient rehabilitation unit is recommended.

Further Outpatient Care

• This also depends on the degree of the head injury and the individual patient's cognitive and motor abilities and pain complaints.

In/Out Patient Meds

• See Medical Care.

Transfer

• Patients with moderately severe or severe head injuries and head injuries with significant extracranial components are cared for best at a specialized trauma center.

Deterrence/Prevention

• Reducing morbidity and mortality rates associated with head injuries is likely to be difficult. Violence, automobiles, and drug and alcohol use are prevalent in Western culture.
• A study of community-based programs reported modest success, primarily by employing increased police surveillance and law enforcement to reduce overdrinking and alcohol-related injuries. Motor vehicle accidents in which the driver was intoxicated declined 6%, and more significantly, overall assault cases seen in local emergency departments decreased 42%.
• Another study has shown that patients who were screened for alcohol problems and provided with an organized intervention to reduce their alcohol consumption exhibited a 47% decrease in emergency department–evaluated injuries compared to patients receiving no alcohol screening or intervention.
• The use of protective devices also is promising. A meta-analysis of case-control studies of bicycle helmet use concluded that helmets reduce the risk of severe head and brain injuries by 63-88%. Indeed, a 2006 study of 160 cyclist injuries in Singapore found that helmet users sustained head injuries only 5.9% of the time, compared with 40% of the time for nonusers. Similarly, a California law mandating the use of bicycle helmets for riders aged 17 years and younger reduced traumatic brain injuries by 18%. However, subgroup analysis revealed that this reduction failed to apply to urban, female, and African American riders.

Complications

• Mild head injury
• • Mild head injuries are those that generate GCS scores of 13-15. Such injuries usually are considered relatively benign, and the accompanying cognitive impairments typically resolve within 3 months of injury.
  • Patients with lingering complaints often are assumed to have either a psychological reaction to the injury or to be "faking." A recent review of mild head injury reported that 33-47% of patients with head injuries who are embroiled in litigation outright malinger. One practitioner from Australia reported that of his 414 patients with closed head injuries, those with more severe injuries were less likely to report persistent head or neck pain than those with milder injuries.
  • However, an initial grading of "mild" does not necessarily mean a mild outcome. As many as 3% of patients with an initial mild injury may require a neurosurgical operation. Some patients have died hours after sustaining trivial head injuries. Also, as previously mentioned, axonal damage has been documented pathologically with mild head injuries.
  • Disability rates may be pronounced with putatively mild injuries as well. Recent studies have demonstrated that following mild head injury, only 54-79% of patients are able to return to full preinjury employment. Another study of 148 patients with mild head injury discovered that after 1 year, 26% had moderate disability and 3%, severe disability. Significant neuropsychological dysfunction, primarily of attentional and memory domains, may persist after mild head injury alone. Irritability and fatigue may linger as well.
• Second impact syndrome
• • In the United States, athletic competitions account for 300,000 mild head injuries per year. The second impact syndrome occurs when an athlete suffers a minor concussion and subsequently is re-injured in play. The repeated concussive events are theorized to result in autoregulatory dysfunction and vascular congestion. Catastrophic brain edema, herniation, and sudden death may ensue.
  • At least 35 cases occurred among US football participants from 1980-1993, but the general incidence of this syndrome is unknown. Concerns about athletes at risk returning to play too soon have generated formalized recommendations from the American Academy of Neurology. Return to play is postponed for increasing lengths of time depending on the severity of the concussion.
  • Some researchers have questioned the existing literature's documentation of initial injuries, hypothesizing that the second impact syndrome is more one of primary impact and that secondary prevention strategies are not justified empirically. Nevertheless, the second impact syndrome maintains a large role in the contemporary management of sports-related brain injuries.
• Posttraumatic epilepsy
• • Posttraumatic seizures occur clinically in approximately 4% of patients with head injuries within the first week of the head injury. Continuous EEG monitoring has disclosed a higher incidence (22%).
  • Seizures after the first week occur in 4-30% of patients. The severity of the head injury, early seizures, depressed skull fractures, and temporal and frontal injuries identified on CT scans all have been associated with the development of late seizures.
  • Although focal EEG findings traditionally have not been predictive of late seizures, one recent study reported that a focal EEG 1 month after injury resulted in a 3.49-times higher risk of posttraumatic epilepsy.
  • Recently, MRI-visualized hippocampal sclerosis has been associated with intractable epilepsy in patients who sustained moderate-to-severe head injuries when aged 10-31 years.
• Posttraumatic headaches
• • Posttraumatic headaches are common and may occur in 30-80% of patients after a head injury. The alterations in cations, catecholamines, and excitatory amino acids are similar in both migraine and head injury.
  • Posttraumatic headaches typically manifest with a vascular component, but chronic daily headaches are also common.
  • Although controversial, some authors have reported that most posttraumatic headaches are primarily rebound or analgesic-overuse headaches. Nearly three fourths of such patients may benefit from cessation of pain medications.
  • Greater occipital neuralgia can occur following head and neck injuries. Greater occipital nerve pain occurs in the back of the head and may be characterized by lancinating or aching sensations in this region.
• Posttraumatic movement disorders
  • Tremor, dystonia, parkinsonism, myoclonus, and hemiballism all can occur following head injuries.
  • In a 2-year follow-up study of 398 patients with severe head injuries, 12% had persistent movement disorders. Disabling dystonia and low-frequency kinetic tremors were present in 5.4%. Parkinsonism and myoclonus attributable to the injury occurred in less than 1% of patients.
• Posttraumatic psychiatric disorders
  • Disorders of emotional functioning have been documented repeatedly after head injuries. A review of 10 studies has estimated that major depression occurs in approximately 44% of patients with head injury. Depression has been associated with left frontal injuries. Bipolar disorder is also more frequent in patients with head injuries than in the general population and is associated with seizures and right hemispheric lesions.
  • Additionally, impulsive and disinhibited behaviors are common in patients with frontal injuries, although even obsessive-compulsive features have also been reported.
  • Head injury-related psychosis is controversial. A case-control study of 45 patients with psychosis following head injury found that auditory hallucinations and paranoid delusions developed after a 54-month postinjury latent period. More widespread injury on neuroimaging and decreased cognitive functioning characterized the psychotic head-injured patients in comparison to nonpsychotic control patients with head injuries.

Prognosis

• This discussion has delineated a myriad of prognostic factors. Head injuries may result in death, a vegetative state, partial recovery, or full return to work. Each patient presents with a unique baseline neurological make up, mechanisms of injury, secondary complications, and postinjury adjustment and support system.
• The most important prognostic factors are probably age, mechanism of injury, postresuscitation GCS score, postresuscitation pupillary reactivity, postresuscitation blood pressures, intracranial pressures, duration of posttraumatic amnesia or confusion, sitting balance, and intracranial pathology identified on neuroimaging.
• The mortality rate of severe head injuries ranges from 25-36% in adults within the first 6 months after injury. Most deaths occur within the first 2 weeks.
• • One study reported that at least 53% of 300 survivors of a severe head injury were either severely disabled or in a vegetative state at the time of hospital discharge.
  • A more recent study found that 29% of survivors were either vegetative or severely disabled after 6 months of follow-up care.
  • Conversely, 82% of 67 patients with mild or moderate head injury experienced a good 1-year outcome, and 73% were able to return to work. However, subjective complaints persisted in a large minority, with more than one third of patients reporting drowsiness, fatigue, forgetfulness, poor concentration, and irritability. Other studies have identified dizziness along with analgesic and psychotropic medication use as predictors of failure to return to work after mild and moderate head injuries.
• An Australian study of patients with head injuries incurred from 1984-1991 found that all 59 patients who were aged 65 years or older and scored less than 11 on the postresuscitation GCS either died or were left with severe disability. Future studies are needed to determine whether this grim prognostic indicator has more universal validity.

Patient Education

• The physician may be hesitant to suggest to patients that problems may arise from a mild head injury. Such information may induce the expectations of symptoms when no symptoms are present and arouse anxiety. However, at least one study has shown that patients with head injury who were contacted by phone and offered education about their injury and follow-up care experienced significantly fewer postconcussive symptoms and less disruption of social activities.
• At present, most patients incurring a head injury probably should be informed that cognitive and emotional dysfunction as well as head pain and other somatic symptoms are not uncommon in the aftermath. At least in mild injuries, these symptoms typically are self-limited, and most people return to normal functioning after a few weeks to months.
• For excellent patient education resources, visit eMedicine's Back, Ribs, Neck, and Head Center, Dementia Center, and Eye and Vision Center. Also, see eMedicine's patient education articles Concussion, Dementia in Head Injury, and Black Eye.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Head injuries and their sequelae are embedded inextricably in the medicolegal system. Both malpractice suits and tort litigation arise from the acute and long-term care of patients with head injuries.
• • A detailed history, review of systems, and complete examination is therefore essential.
  • Incorporate previous head pain, psychiatric treatments, and medication failures in the medical history.
  • Procure prior medical records, if possible, from emergency departments and other treating physicians.
  • Vague prior head injuries may become significant if emergency records report orofacial trauma or other clinical features that subsequently were forgotten or deemed unimportant by the patient and significant others.
  • Conversely, the patient's denial of preinjury head pain also may be significant if prior medical records reveal past treatment for migraines.
• Documentation should be meticulous.
• • The physician must substantiate that a certain event likely induced a brain injury; delineate the physical, emotional, and cognitive consequences of that injury; and arrive at a prognosis for recovery.
  • The physician's findings and conclusions should rest securely on accessible and up-to-date published medical literature.
• Relying on ancillary personnel or testing to the exclusion of the examiner's own evaluation can be perilous.
• • Subtle MRI abnormalities may not be included in the radiology report.
  • The author recently examined an individual with purported remote head injury who easily copied complicated figures and drew and labeled a clock face, although a few weeks previously this same patient performed 3 standard deviations below the mean on a judgment of line orientation test. Such discordance between bedside and quantitative neuropsychological testing certainly broadens the differential diagnosis.
• Adequately addressing long-term functional impairments is also paramount.
• • Driving independently is of particular importance to most patients. Although estimating driving ability on the basis of cognitive testing is difficult, some have found that visual spatial skills, reaction times, and awareness of deficits correlate with driving abilities. In some cases, actual road tests may be needed.
  • Finally, patients with pain and emotional complaints that are refractory to standard management must receive documented referrals to appropriate specialists.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction