- Author: David A Olson, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more...
Head injury can be defined as any alteration in mental or physical functioning related to a blow to the head (see the image below). According to the Centers for Disease Control and Prevention (CDC), 50,000 individuals die from traumatic brain injuries each year in the United States. Almost twice that many people suffer permanent disability.
Essential update: Two phase 3 trials find progesterone does not improve functional outcome in TBI
In a pair of randomized, controlled multicenter studies, the neurosteroid progesterone showed no beneficial effect on functional outcomes in patients with acute traumatic brain injury (TBI).[1, 2, 3, 4]
The first trial, the double-blind PROTECT (Progesterone for the Traumatic Brain Injury, Experimental Clinical Treatment) III study in patients with severe, moderate-to-severe, or moderate acute TBI, found no significant difference in favorable outcomes between treatment and placebo groups; the trial was halted after enrollment of 882 of 1140 planned participants. Subjects in the progesterone group had higher rates of phlebitis or thrombophlebitis than those in the placebo group.
In the second study, SYNAPSE (the Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury), 1195 patients with severe TBI were assigned to receive either progesterone or placebo. Similar rates of favorable outcomes and mortality were observed in the two groups.
Signs and symptoms
The Glasgow Coma Scale (GCS) is the mainstay for rapid neurologic assessment in acute head injury. Following ascertainment of the GCS score, the examination is focused on signs of external trauma, as follows:
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
Anosmia: Common; probably caused by the shearing of the olfactory nerves at the cribriform plate 
Abnormal postresuscitation pupillary reactivity: Correlates with a poor 1-year outcome
Isolated internuclear ophthalmoplegia secondary to traumatic brainstem injuries: Has a relatively benign prognosis 
Cranial nerve (CN) VI palsy: May indicate raised intracranial pressure
CN VII palsy: May indicate a fracture of the temporal bone, particularly if it occurs in association with decreased hearing
Hearing loss: Occurs in 20-30% of patients with head injuries 
Dysphagia: Raises the risk of aspiration and inadequate nutrition 
Focal motor findings: Include flexor or extensor posturing, tremors and dystonia, impairments in sitting balance, and primitive reflexes; may be manifestations of a localized contusion or an early herniation syndrome
See Clinical Presentation for more detail.
Bedside cognitive testing
In the acute setting, measurements of the patient's level of consciousness, attention, and orientation are of primary importance.
Some patients acutely recovering from head trauma demonstrate no ability to retain new information. Mental status assessments have validated the prognostic value of the duration of posttraumatic amnesia; patients with longer durations of posttraumatic amnesia have poorer outcomes.
In the long-term setting, the following bedside cognitive tests can be employed:
Mini-Mental State Examination
Luria "fist, chop, slap" sequencing task: To rapidly assess motor regulation
Antisaccade task: Impaired in patients with symptomatic brain injury; the sensitivity of this test in detecting brain injury has been questioned 
Letter and category fluency: To provide information about self-generative frontal processes.
Untimed Trails B test: Allows further qualitative testing of frontal functioning
Sodium levels: Alterations in serum sodium levels 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; elevated sodium levels in head injury indicate simple dehydration or diabetes insipidus
Magnesium levels: These are depleted in the acute phases of minor and severe head injuries
Coagulation studies: Including prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count; these are important to exclude a coagulopathy
Blood alcohol levels and drug screens: May help to explain subnormal levels of consciousness and cognition in some patients with head trauma
Renal function tests and creatine kinase levels: To help exclude rhabdomyolysis if a crush injury has occurred or marked rigidity is present
Neuron-specific enolase and protein S-100 B: Elevated serum levels may correlate with persistent cognitive impairment at 6 months in patients with severe or mild head injuries 
Computed tomography scanning: The main imaging modality used in the acute setting
Magnetic resonance imaging: Typically reserved for patients who have mental status abnormalities unexplained by CT scan findings
Although certain electroencephalographic patterns may have prognostic significance, considerable interpretation is needed, and sedative medications and electrical artifacts are confounding. The most useful role of electroencephalography (EEG) in head injuries may be to assist in the diagnosis of nonconvulsive status epilepticus.
See Workup for more detail.
If the intracranial pressure rises above 20-25 mm Hg, intravenous mannitol, cerebrospinal fluid drainage, and hyperventilation can be used. If the intracranial pressure does not respond to these conventional treatments, high-dose barbiturate therapy is permissible.
Another approach used by some clinicians is to focus primarily on improving cerebral perfusion pressure as opposed to intracranial pressure in isolation.
Decompressive craniectomies are sometimes advocated for patients with increased intracranial pressure refractory to conventional medical treatment.
Dantrolene, baclofen, diazepam, and tizanidine are current oral medication approaches to hypertonicity. Baclofen and tizanidine are customarily preferred because of their more favorable side-effect profiles.
Traditionally, the prompt surgical evacuation of subdural hematomas was believed to be a major determinant of an optimal outcome. However, research indicates that the extent of the original intracranial injury and the generated intracranial pressures may be more important than the timing of surgery.
Head injury can be defined as any alteration in mental or physical functioning related to a blow to the head. Loss of consciousness does not need to occur. The severity of head injuries is most commonly classified by the initial postresuscitation Glasgow Coma Scale (GCS) score, which generates a numerical summed score for eye, motor, and verbal abilities. Traditionally, a score of 13-15 indicates mild injury, a score of 9-12 indicates moderate injury, and a score of 8 or less indicates severe injury. In the last few years, however, some studies have included those patients with scores of 13 in the moderate category, while only those patients with scores of 14 or 15 have been included as mild. Concussion and mild head injury are generally synonymous.
Research on head injury has advanced considerably in the last decade. As is typical of many endeavors, these efforts have exposed the complexity of this condition more deeply and have helped researchers and physicians to abandon crude simplifications. This review concentrates primarily on current developments in the diagnosis and management of closed head injuries in adults.
Gross structural changes in head injury are common and often obvious both on autopsy and conventional neuroimaging. The skull can fracture in a simple linear fashion or in a more complicated depressed manner, in which bone fragments and pushes beneath the calvarial surface. In patients with mild head injury, a skull fracture markedly increases the chance of significant intracranial injury.
Both direct impact and contrecoup injuries, in which the moving brain careens onto the distant skull opposite the point of impact, can result in focal bleeding beneath the calvaria. Such bleeding can result in an intracerebral focal contusion or hemorrhage as well as an extracerebral hemorrhage. Extracerebral hemorrhages are primarily subdural hemorrhages arising from tearing of bridging veins, but epidural hemorrhages from tearing of the middle meningeal artery or the diploic veins are also common. Occasionally, subdural hemorrhages can result from disruption of cortical arteries. This type of subdural hemorrhage is rapidly progressive and can occur after trivial head injury in elderly patients.
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.
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 a mouse model of head injury, elevated levels of the transcription factor p53 were found. p53 translocates to the nucleus and initiates apoptosis or programmed cell death. Such a process could account for the delayed neuronal loss seen in head injuries.
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.
Severe anemia is often coexistent with head injuries, but blood transfusions have been recently associated with increased mortality and complications among 1,250 ICU-admitted patients with brain injuries. This relationship held even after controlling for the degree of anemia.
Finally, posttraumatic cerebral infarction occurs in up to 12% of patients with moderate and severe head injuries and is associated with a decreased Glasgow Coma Scale, low blood pressure, and herniation syndromes.
In the United States, 1.5 million individuals per year incur a head injury. Of these injuries, 75% are classified as mild. Between 1998 and 2000, the incidence of mild traumatic brain injury was 503 cases per 100,000 persons, with a doubling of this incidence in Native Americans and children.
In 2003, elderly persons with head injuries exhibited a doubling in hospitalizations and deaths compared to the national average.
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.
European rates of hospitalization for head injury have ranged from 91 cases per 100,000 persons per year in Spain in 1988 to 313 cases per 100,000 persons per year in Scotland from 1974-1976. In New Zealand, 782 cases per 100,000 of mild head injury were seen in hospitals or emergency rooms in 1986.
Head injury data are difficult to compare internationally for multiple reasons, including inconsistencies and complexities of diagnostic coding and inclusion criteria, case definitions, ascertainment criteria (for example, hospital admissions versus door-to-door surveys), transfers to multiple care facilities (for example, patient admissions may be counted more than once), and regional medical practices, such as the aforementioned recent development in the United States of more outpatient, as opposed to inpatient, services for those with mild head injuries. Adding to this complexity is the finding that some individuals with cognitive and emotional sequelae from mild head injury may not establish the casual connection between their injury and its consequences. Such patients may not seek treatment and may not be expressed in official demographic data.[35, 36]
According to the CDC, 50,000 individuals die from traumatic brain injuries each year in the United States. Almost twice that number suffer permanent disability.
A study of intentional head injury from Charlotte, North Carolina, found minority status was a major predictor of intentional head injury, even after controlling for other demographic factors. Furthermore, worse clinical outcomes have been described for African American children with moderate-to-severe head injuries compared with their white counterparts.
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.
Approximately half of the patients admitted to a hospital for head injury are aged 24 years or younger.
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