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), more than 50,000 individuals die from traumatic brain injuries each year in the United States. Almost twice that many people suffer permanent disability. In the United States in 2013, about 2.8 million emergency department (ED) visits, hospitalizations, or deaths were associated with TBI—either alone or in combination with other injuries.[1, 2]
View Image
This 50-year-old woman with epilepsy seized and struck her head. Her initial Glasgow Coma Scale score was 12. Her scan shows prominent right temporal ....
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[3]
Abnormal postresuscitation pupillary reactivity: Correlates with a poor 1-year outcome
Isolated internuclear ophthalmoplegia secondary to traumatic brainstem injuries: Has a relatively benign prognosis[4]
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[5]
Dysphagia: Raises the risk of aspiration and inadequate nutrition[6]
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.
Diagnosis
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.[7]
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[8]
Letter and category fluency: To provide information about self-generative frontal processes.
Untimed Trails B test: Allows further qualitative testing of frontal functioning
Laboratory studies
Sodium levels: Alterations in serum sodium levels occur in as many as 50% of comatose patients with head injuries[9] ; 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: Although earlier studies suggested that elevated serum levels may correlate with persistent cognitive impairment at 6 months in patients with severe or mild head injuries, current opinion considers these tests no longer useful.[10, 11]
In 2018, a commercially available blood test for mild brain injury was approved by the FDA.[12] This test reportedly identifies 98% of patients with abnormal head CT scans.
Imaging studies
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
Electroencephalography
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.
Management
Intracranial pressure
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.[13]
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.
Hypertonicity
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.
Subdural hematomas
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.[14] 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.[15]
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.[16]
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.[17]
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.[18] More severe and diffuse axonal injury has been found to correlate with vegetative states and the acute onset of coma following injury.[19]
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).[20] In addition, 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.[21]
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.[22] 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.[23]
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.[24] 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.[25] Delayed clinical deterioration could represent ischemia from such vasospasm, particularly in younger patients.[26]
Head injury also causes the release of free radicals and the breakdown of membrane lipids. Panels of plasma metabolites related to fatty acid and lipid breakdown products have been found to be elevated in mildly concussed athletes compared to controls.[27]
Other inflammatory biomarkers have yielded complex and contradictory results. However, overall some initial inflammation may promote recovery, but prolonged or high levels of inflammation could be detrimental.[28, 29] For example, in severely brain-injured patients a group of CSF inflammatory mediators including intraleukin 6 and 8 discriminated between good versus poor 6-month outcomes with higher levels of these inflammatory mediators occuring in those with poorer outcomes.[30]
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.[31] Furthermore, in humans, differential activation of inflammatory regulatory genes has been associated with the worse outcomes observed in elderly patients with closed head injuries compared to their younger counterparts.[32]
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.[33] More current epidemiologic research supports the lack of benefit of early intubation.[34]
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.[35]
Severe anemia is often coexistent with head injuries, but blood transfusions have been associated with increased mortality and complications among 1250 ICU-admitted patients with brain injuries. This relationship held even after controlling for the degree of anemia.[36] Similarly, adverse thromboembolic events occured among 200 severely head-injured patients treated wtih erythropoetin and transfusions.[37]
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.[38]
In the United States, 2.8 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. Between 2007 and 2012, brain injury hospitalizations, death, and emergency department visits increased from 640 to 890 cases per 100,000 persons in the United States.[1, 2]
In 2003, elderly persons with head injuries exhibited a doubling in hospitalizations and deaths compared to the national average.[39] This trend has persisted with Canadian, European, and US data demonstrating an increased frequency and severity of traumatic brain injury in the elderly, primarily secondary to falls, while motor vehicular causes have decreased.[40, 41, 42, 2]
International
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 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.[43, 44]
Despite such obstacles, a recent meta-analysis extrapolated head injury rates to total population estimates and found that Southeast Asian and Western Pacific nations carried the heaviest global head injury burden.[45]
Mortality/Morbidity
According to the CDC, about 56,000 individuals die from traumatic brain injuries each year in the United States. Almost twice that number suffer permanent disability.[2]
Race
A study of intentional head injury from Charlotte, North Carolina, found minority status was a major predictor of intentional head injury, even after controlling for other demographic factors.[46] Furthermore, worse clinical outcomes have been described for African American children with moderate-to-severe head injuries compared with their white counterparts.[47]
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. The rates of emergency room visits for the head-injured elderly are more than 3 times higher for those over 84 years of age compared to those between 65 to 74 years of age.[48]
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.[46]
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.
Among high school athletes with head injuries, on-field “dizziness,” but not objective balance impairments, at the time of concussion significantly correlated with prolonged return to play compared to athletes with head injuries who did not experience this symptom.[49]
Carefully consider past psychiatric disease and a premorbid history of headaches.
The Glasgow Coma Scale (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.[3] If accompanied by rhinorrhea, a CSF leak with the attendant risk of ascending meningitis must be excluded.[50]
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[51] , while other researchers have demonstrated that only 9% of 92 such patients attained good outcomes[52] . A unilaterally dilated pupil with or without evidence of ipsilateral cranial nerve (CN) III paralysis, such as ptosis or impaired ocular motility, may indicate impending herniation.
Isolated internuclear ophthalmoplegia secondary to traumatic brainstem injuries has been described and has a relatively benign prognosis.[4]
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.
Hearing loss is also frequent with sensory neural loss occurring in 20-30% of patients with head injuries. Low-frequency loss typically improves after 1 year.[5]
Dysphagia raises the risk of both aspiration and inadequate nutrition.[6]
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.[53]
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.[54]
Primitive reflexes, despite their presence in some healthy elderly patients, are useful and when multiple can correlate with cognitive deficits.
Bedside cognitive testing
See the list below:
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.[55]
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.[7]
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" may be a more accurate descriptor.[56]
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.[57]
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, 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 brain injury compared to controls, although the sensitivity of this test in detecting brain injury has been questioned.[8]
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.[58]
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. The incidence of fall-related traumatic brain injury has been increasing in the United States and in 2013 resulted in 12,015 deaths and 91,470 hospitalizations in the elderly.[2]
Blast injuries from incendiary devices can cause head trauma and primarily occur in soldiers, although even civilian tire explosions have been implicated.[59] While the energy from the blast can directly impact the cranium and be transferred to the brain, some researchers have hypothesized that systemic blood vessels may actually transmit the shock waves.[60] Current clinical studies, however, have failed to identify a unique pattern of neuropsychologic deficits in patients who have incurred such blast injuries.[61]
Anticoagulants and antiplatelet medications, such as aspirin, raise the risk of intracranial bleeding with even trivial head injuries.[62] For example, among elderly patients with head injuries, clopidogrel use has been associated with a 15 times greater mortality compared with patients not taking antithrombotics.[63] Head-injured warfarin users, compared to direct oral anticoagulant users, exhibited a greater mortality and greater need for neurosurgical procedures.[64] Curiously, another study documented counterintuitively that in patients with mild head injury, antiplatelet agent use more than doubled the risk of intracranial bleeding compared to anticoagulant use.[65]
Alcohol use raises the risks of incurring a head injury. Perhaps because it may impede excitotoxicity, alcohol use at the time of injury may actually decrease the likelihood of a poor outcome.
A newer study of intentional head injuries reported that patients consuming alcohol had higher initial GCS scores.[46] 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). Methamphetamine use has also been shown to reduce mortality in severe head injury.[66] More recently, patients with severe brain injuries and high blood alcohol levels (≥ 0.08 mg/L) exhibited a significantly lesser mortality compared with patients with lower levels or the absence of alcohol in their blood.[67]
The presence of even one of the alleles for the APOE4 genotype may increase the risk of a poor outcome.
An earlier study reported that 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.[68]
Football players and boxers with an APOE4 allele are at greater risk for posttraumatic cognitive problems than APOE4 -negative athletes.[69] Similarly, possesion of an APOE4 allele was associated with worse verbal memory after even mild head injuries compared to other APOE genotypes.[70]
Other studies have called these APOE4 associations into question, but a 2008 meta-analysis as well as a 2015 one has supported these observations.[71, 72]
Genes regulating the interleukin, dopamine, and apoptotic systems as well as genes associated with angiotensin converting enzyme and calcium channel polymorphisms have all been implicated in head injury outcomes.[73] For example, a polymorphism in the dopaminergic alpha-synuclein promoter gene has been correlated with poor memory in mildly head-injured adults.[74] Furthermore, a polymorphism of the IL-6 receptor tripled the risk of concussions in athletes over those lacking this allelic variant.[75] Other genetic determinants of head injury will undoubtedly surface with further research.
Alterations in serum sodium levels are critical and occur in as many as 50% of comatose patients with head injuries.[9]
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.[76] The incidence of cerebral salt wasting ranges from 1% to 35% of head-injured patients.[77]
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.[78]
Coagulation studies, including prothrombin times (PT), activated partial thromboplastin times (aPTT), and platelet counts, are important to exclude a coagulopathy. A limited trauma-induced coagulopathy as evidence by prolonged PT levels has been found in patients hospitalized for head injury, but PT levels return to normal after 12 hours and the clinical importance of this prolongation is currently unclear.[79]
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.
Older studies have demonstrated that elevated serum levels of neuron-specific enolase and protein S-100 B obtained within 24 hours of head injury correlated with persistent cognitive impairment at 6 months in patients with severe or mild head injuries.[11] However, neuron-specific enolase and S-100 B elevations have even been correlated with frequent "headings" of balls during soccer playing.[80] Unfortunately, even vigorous soccer training alone increases serum S-100 B as much as playing and heading does, calling into question the specificity of S-100 B as a biomarker of head injury.[81] Furthermore, a 2018 review of neuron-specific enolase in mild head injuries found this marker to be poorly correlated with both symptoms and measures of cognitive functioning.[82]
More recently, utilizing a unique serum immunoassay, elevation of neurofilament light (an axonal breakdown product) measured on day 6 post-injury identified those hockey players with perisistent post-concussive symptoms from those who were able to return to play.[83]
Although other research on patients with mild closed head injuries has found that increased glial fibrillary acid protein (GFAP) levels correlated with abnormal neuroimaging, both GFAP and S100B failed to significantly correlate with clinical outcomes.[84] Nevertheless, combining serum elevations of GFAP along with heart fatty acid binding protein predicated abnormal head CT findings in mildly head injured (GCS 15) patients,[85] and the FDA has recently approved a blood test for head injury combining GFAP and a ubiquitin derivative.[12]
Computerized tomography (CT) is the main imaging modality used in the acute setting.
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.[86] More complicated criteria have been invoked to predict abnormal head CT scans even without loss of consciousness; however, these rules are cumbersome.[87] Further validation of such imaging rules is needed. In the specific case of the elderly with syncope and a subsequent fall, dramatically increased rates of CT abnormalities have been observed.[88]
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.[89]
In addition, emergent brain imaging may be performed for nonmedical reasons. A 10-year study of elderly women with closed head injuries revealed that in general, emergency department physicians who practice in states with tort reform laws ordered significantly less neuroimaging studies than those physicians who practice in states without such legislation.[90]
See the images below.
View Image
This 50-year-old woman with epilepsy seized and struck her head. Her initial Glasgow Coma Scale score was 12. Her scan shows prominent right temporal ....
View Image
This 40-year-old woman was anticoagulated with warfarin (Coumadin) and fell out of her hospital bed. She subsequently died. Her CT scan shows an obvio....
MRI
Magnetic resonance imaging (MRI) is typically reserved for patients who have mental status abnormalities unexplained by CT scan findings. 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.[91]
Furthermore, increased total lesion volume on fluid-attenuated inversion-recovery (FLAIR) MRI images has been demonstrated to correlate with poor clinical outcomes as well.[92]
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.
See the image below.
View Image
This 35-year-old man was in a motor vehicle accident. His initial Glasgow Coma Scale score was 7. He had left hemiparesis. He recovered orientation to....
Diffusion tensor imaging may document axonal pathologies in patients with head injury even when conventional MRI scans are unremarkable. For example, diffusion tensor imaging has identified impaired water diffusion indicating white matter tract disruption in patients with mild head injuries whose MRI scans were normal. Cortical projection fibers were frequently abnormal, and using an innovative fiber tracking methodology, actual disruption of cortical projection fibers could be visualized in 19% of fiber groups studied.[93] Similarly, attention impairments in patients with mild head injuries have recently been correlated with diffusion abnormalities in cortical projection fibers.[94] Furthermore, utilizing this methodology, aggresive behavior in mildly head injured patients has been correlated with reduced white matter in the corpus callosum.[95] Finally, in severe head injuries, reduced track length and reduced track number have correlated with a worse 6-month mortality.[96]
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.[97] 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.[98]
Proton magnetic resonance spectroscopy of frontal white matter that appears normal on MRI has shown a decrease in neuronal N-acetylaspartate spectra and an increase in choline spectra in patients with head injuries indicating neuronal loss.[99, 100]
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. Although a landmark study of continuous EEG monitoring in patients hospitalized with traumatic brain injury had found convulsive and nonconvulsive seizures in 22% of their subjects.[101] more recent investigations have found subclinical seizures in only 3.8% of brain-injured patients monitored with continuous EEG.[102]
A 2012 study reported that severe slowing on continuous EEG monitoring related to delta waves or burst suppression patterns is associated with poor outcomes at 3 and 6 months in patients with traumatic brain injuries.[103]
A 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.[104]
Although a comprehensive discussion of the histology of traumatic brain injury is beyond the scope of this article, several important newer immunohistochemical techniques have further elucidated the pathophysiology of brain injury.
Beta-amyloid precursor protein is made in the neuron and transported to the axon. The shear forces incurred in head injury damage the axon and beta-amyloid accumulates proximal to the injury. Special immunohistochemical stains for this substance have detected beta-amyloid accumulation as early as 35 minutes after severe head injuries in humans.[105]
As mentioned previously, apoptosis (programmed cell death) is initiated in brain trauma and may account for delayed loss of functioning. Using a combination of enzymatic and immunohistochemical marking, the DNA fragmentation accompanying apoptosis has been documented in human trauma patients and occurs from 2 hours to 12 days after the initial injury.[106]
Chronic repetitive head injuries in athletes results in a tauopathy, which was previously known as dementia pugilistica (it is not confined to boxers alone). Tau reactive neurofibrillary tangles and astrocytic tangles accumulate primarily in the frontal and temporal cortices in irregular patches, preferentially occupying the depths of sulci.[107] In afflicted patients, initial psychiatric symptoms of depression and behavioral dyscontrol progress to a debilitating dementia.[108] This syndrome is now known as Chronic Traumatic Encephalopathy (CTE). Indeed, fragments of tau have been identified in the plasma of concussed hockey players, offering yet another serum biomarker of closed head injury.[109]
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.[33]
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 a recent meta-analysis found no evidence of diminished mortality or improved ICP control with this treatment.[110] More definitive studies are obviously needed.[111] 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.)[13]
Interestingly, a 2008 study utilizing the National Trauma Data Bank retrospectively uncovered a 45% reduction in survival in patients who underwent intracranial pressure monitoring.[112] 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.[113]
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.[114] 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.[115]
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.[116]
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.[117] Furthermore, a current review of 23 randomized, controlled trials concluded that this therapy was of no benefit.[118]
Although acute hypothermic treatment has been found to worsen outcomes in patients with diffuse head injuries, it may improve outcomes in patients with surgically-evacuated hematomas. This indicates a potential benefit in this subgroup; however, further prospective studies are needed.[119] Current opinion holds that therapeutic hypothermia administration should be reserved only for clinical trials.[120]
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.[121]
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.[122] 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.[123] 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.[124] Steroid-induced hyperglycemia may have been detrimental as a recent meta-analysis found careful glucose regulation improved functional outcomes in head-injured patients.[125]
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.[126] A trial of valproate in early seizure prophylaxis showed a trend toward an increased mortality rate. Because of its relatively benign side-effect profile, levetiracetam has been increasingly employed to prevent post-traumatic seizures, but its efficacy has not been empirically validated.[127] Indeed, a retrospective review of 5551 acutely brain-injured patients found no significant difference in seizure rates between the patients prophylaxed with levetiracetam and the patients who were untreated, calling into question the routine practice of employing levetiracetam for seizure prophylaxis.[128] Anticonvulsant therapy, if used, should be discontinued after 1–2 weeks unless further seizures supervene.[129]
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.[130]
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.[131]
Although promising in rodents, in a recent pair of randomized, controlled multicenter studies, the neurosteroid progesterone showed no beneficial effect on functional outcomes in patients with acute traumatic brain injury.[132, 133, 134, 135]
The first trial, the double-blind PROTECT (Progesterone for the Traumatic Brain Injury, Experimental Clinical Treatment) III study in patients with severe to moderate acute traumatic brain injury, found no significant difference in favorable outcomes between treatment and placebo groups; the trial was halted after enrollment of 882 of 1140 planned participants.[132] 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 traumatic brain injury were assigned to receive either progesterone or placebo.[133] Similar rates of favorable outcomes and mortality were observed in the two groups.
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.[136]
More conventional agents have also included propranolol in a large, non-randomized prospective trial. When initiated within the first 24 hours in patients with moderate to severe head injuries, propranolol significantly reduced mortality, presumable by blocking the catecholamine surge that accompanies the initial injury.[137] A recent randomized trial of erythropoetin also showed promising effects with 33% of treated severely head-injured patients exhibiting a good recovery compared to only 13% of controls.[138]
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.[139] More encouraging but less rigorous was a retrospective analysis of traumatic brain-injured patients that found decreased mortality among those patients with THC in their urine compared to those without this substance.[140]
Rosuvastatin given in the acute phase of moderate head injury significantly reduced amnesia in a double-blind placebo-controlled study of 34 patients.[141] Other research has retrospectively found that statin use was associated with a decreased mortality in a large, 100,515 patient cohort of brain injured elderly.[142] Furthermore, a randomized prospective trial of atorvastatin demonstated improved functional outcomes at 3 months post-injury in patients with brain contusions who were treated with a mere 10-day course.[143]
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.[144] Furthermore, an open-label study of children and adolescents with traumatic brain injuries reported not only a shortened duration of post-traumatic amnesia but also reduced subjective symptoms in those treated with oral creatine for 6 months compared to those not treated.[145] Melatonin is a free-radical scavenger, and when injected early in brain-injured rats, it significantly reduced levels of lipid breakdown products.[146]
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.[147]
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.[148, 149]
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.[150] 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.[151]
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.[152] Other less rigorous studies have also reported cognitive improvements in donepezil-treated, head-injured patients.[153]
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.[154] Furthermore, levodopa has even produced qualitative cognitive improvements in a small number of head-injured patients.[155]
Emotional lability and the pathologic laughing and crying associated with pseudobulbar palsy reportedly have responded rapidly and exquisitely to not only selective serotonin reuptake inhibitors but also possibly to dextromethorphan with quinidine.[156, 157] Sertraline has shown efficacy in depression in mild head injury.[158] 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.
Nonmedical therapy
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.[159]
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.[160]
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.[161] 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.[162]
Subdural hematomas less than 5mm in thickness seldom require surgical attention.[163]
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.[164]
Among 77 mild brain-injured patients with small subarachnoid bleeds, non-displaced skull fractures, and subdural hematomas less than 4mm, only 1.3% required a formal neurosurgical consult. The vast majority of patients were managed by trauma surgeons alone with no untoward complications.[165]
Decompressive craniectomies are sometimes advocated for patients with increased intracranial pressure refractory to conventional medical treatment. Although some studies have shown favorable long-term outcomes with this procedure[166]
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.
Guidelines for traumatic brain injury are undergoing constant revision with the incorporation of newly completed clinical studies and research.
The American Association of Neurological Surgeons generally does not produce specific treatment guidelines. However, the Brain Trauma Foundation recently published revised guidelines for severe traumatic brain injury, and their recommendations have been endorsed by neurosurgical professional organizations. These guidelines are based on high-to-moderate quality evidence and are summarized below:[167]
1. If decompressive craniectomy is performed, a large frontal, temporal, and parietal one is preferred over smaller craniectomies.
2. There is no evidence that hypothermia improves outcomes.
3. There is insufficient evidence to support a specific hyperosmolar treatment (mannitol or hypertonic saline) for increased intracranial pressure.
4. There is insufficient evidence to support CSF drainage.
5. There is insufficient evidence to support prophylactic hyperventilation.
6. There is insufficient evidence for sedatives, analgesics, or anesthetic agents.
7. Steroids are to be avoided as they increase mortality.
8. Enteral feeding should be initiated within the first week.
9. Early tracheostomy placement is recommended.
10. Povidone-iodine oral care should not be used as this may increase ARDS.
11. There is insufficient evidence to support specific DVT-prevention strategies.
In 2013, the American Academy of Neurology[168] introduced guidelines for concussion in sports. These guidelines endorsed symptom checklists to be used by non-physician assesors to help diagnose concussions. An athlete with an identified concussion is prohibited from returning to play until the signs and symptoms of the concussion have resolved. Athletes with multiple concussions and objective neurologic or cognitive impairments are retired from play.
In 2008, the CDC recommended imaging guidelines for mild traumatic brain injury, which were re-affirmed in 2013. A CT of the head is indicated in patients with head injury and loss of consciousness or amnesia if the patient has also had any of the following: headache, vomiting, age greater than 60 years, drug or alcohol intoxication, short-term memory loss, evidence of trauma above the clavicles, a seizure, a focal neurologic deficit, a GCS less than 15, or a coagulopathy. Such complicated decisions rules seem impractical and will hopefully be clarified with further research.[169]
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.
Clinical Context:
May reduce subarachnoid space pressure by creating osmotic gradient between CSF in arachnoid space and plasma. Not for long-term use. Initially assess for adequate renal function in adults by administering test dose of 200 mg/kg, given IV over 3-5 min; should produce urine flow of at least 30-50 mL/h of urine over 2-3 h. Same test in children should produce urine flow of at least 1 mL/kg/h over 1-3 h.
Clinical Context:
May act in motor cortex, where it may inhibit spread of seizure activity; activity of brainstem centers responsible for tonic phase of grand mal seizures also may be inhibited.
Individualize dose. Administer larger dose in evening if dose cannot be divided equally.
Clinical Context:
Nutritional supplement in hyperalimentation; cofactor in enzyme systems involved in neurochemical transmission and muscular excitability. In adults, 60-180 mEq of potassium, 10-30 mEq of magnesium, and 10-40 mmol of phosphate per day may be necessary for optimum metabolic response.
Clinical Context:
Indicated for improvement of neurological impairments resulting from spasms following subarachnoid hemorrhage caused by ruptured congenital intracranial aneurysm in patients who are in good neurological condition postictus.
While studies show benefit on severity of neurological deficits caused by cerebral vasospasm following subarachnoid hemorrhage, no evidence that drug either prevents or relieves spasms of cerebral arteries. Thus, actual mechanism of action unknown.
Therapy should start within 96 h of subarachnoid hemorrhage. If capsule cannot be swallowed because patient undergoing surgery or unconscious, a hole can be made at both ends of capsule with 18-gauge needle and contents extracted into a syringe. Contents then can be emptied into patients' in situ nasogastric tube and washed down tube with 30 mL isotonic saline.
Clinical Context:
Blocks the reuptake of norepinephrine and dopamine into presynaptic neurons. May stimulate cerebral cortex and subcortical structures.
Clinical Context:
Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system. Absorption decreased by meals, which include other large neutral amino acids. Only patients with meaningful motor fluctuations need consider low-protein or protein-redistributed diet. Greater consistency of absorption achieved when levodopa taken 1 h or more after meals. Nausea often reduced if levodopa taken immediately following meals. Some patients with nausea benefit from additional carbidopa in doses up to 200 mg/d. Half-life of levodopa/carbidopa approximately 2 h.
When more carbidopa required, substitute 1 25/100 tab for each 10/100 tab; when more levodopa required, substitute 25/250 tab for 25/100 or 10/100 tab.
Sustained release (SR) formulation of levodopa/carbidopa is absorbed more slowly and provides more sustained levodopa levels than immediate release (IR) dosage form; SR as effective as IR formulation when levodopa initially required and may be more convenient when fewer intakes are desired.
Patients with dissipating motor fluctuations and no dyskinesia often benefit from prolongation of short-duration response when switched from IR to SR; however, patients with meaningful fluctuations and dyskinesia often experience increase in dyskinesia when switched to SR formulation.
Doses and dosing intervals of SR form may be increased or decreased based on response; most patients have been treated adequately with 2-8 tab/d (divided doses) at intervals of 4-8 h while awake; higher doses (>12 tab/d) and intervals < 4 h have been used but usually are not recommended; if < 4-h interval used or if divided doses are not equal, give smaller doses at end of day. Allow at least a 3-d interval between dosage adjustments. May administer as whole or half tab, which should not be crushed or chewed.
Clinical Context:
SSRIs are antidepressant agents that are chemically unrelated to TCAs, tetracyclic antidepressants (TeCAs), or other available antidepressants. They inhibit central nervous system (CNS) neuronal uptake of serotonin and may have a weak effect on neuronal reuptake of norepinephrine and dopamine.
Clinical Context:
Tizanidine is a centrally acting muscle relaxant that is metabolized in the liver and excreted in urine and feces. A single oral dose of 8mg reduces muscle tone in patients with spasticity for several hours. Blood levels and the spasmolytic effect are linearly correlated.
Clinical Context:
May induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at spinal level. Baclofen presynaptically inhibits the nerve terminal. It is centrally acting and can be administered intrathecally or orally. Baclofen is the preferred drug for spasticity related to spinal cord injury (SCI). Tolerance can occur. Adverse effects are minimized if the drug is given intrathecally.
Clinical Context:
This is a peripherally acting medication that prevents calcium release from the sarcoplasmic reticulum. It is particularly effective in cerebral-origin spasticity, such as that occurring in traumatic brain injury (TBI), stroke, or cerebral palsy. Stimulates muscle relaxation by modulating skeletal muscle contractions at site beyond myoneural junction and acting directly on muscle.
Clinical Context:
Diazepam acts presynaptically and is a gamma-aminobutyric acid ̶ A (GABA-A) agonist. It is centrally acting. Tolerance and addiction can occur.Depresses all levels of CNS, possibly by increasing activity of GABA. Individualize dosage and increase cautiously to avoid adverse effects.
Antispasticity medications can be useful. These agents may reduce painful cramping and detrimental muscle tightening. However, one of the drawbacks of using these agents is that some patients find that the stiffness of spasticity helps them to overcome the muscle weakness. When patients are medicated to reduce stiffness, walking may become more difficult. Adverse effects can also be a problem.
If the patient does well with the medications, however, discomfort associated with spasticity can generally be reduced, mobility can be improved, and the effectiveness of physical therapy (PT) can be enhanced.
Clinical Context:
Dextromethorphan is a sigma-1 receptor agonist and an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Quinidine increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P4502D6, which catalyzes a major biotransformation pathway for dextromethorphan. The mechanism by which dextromethorphan exerts therapeutic effects is unknown.
Glutamate release inhibition and glutamate receptor blockade are alternatives to potentiating D2 receptors in the indirect pallidal outflow pathway by reducing the glutamate-related excitatory circuit in the outflow pathway.
Patients with moderate or severe head injuries and head injuries with significant extracranial components are cared for best at a specialized trauma center.
Reducing morbidity and mortality rates associated with head injuries is likely to be difficult. Violence, automobiles, and drug and alcohol use are prevalent.
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%.[170]
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.[171]
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%.[172] 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.[173] 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.[174]
Falls in the elderly are often multifactorial in origin and consequently, solutions are likely to be complex. Nevertheless, random allocation of indepently living elderly patients to a fall-prevention regime of strength and balance training reduced both the number of falls as well as their severity.[175]
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 are often assumed to have either a psychological reaction to the injury or to be malingering. Various standardized neuropsychologic instruments are available to help sort out legitimate from illegitimate cognitive impairments. About 25% of patients with mild head injury taking such tests yield invalid profiles.[176] Furthermore, coexisting musculoskeletal injuries may impact cognitive testing. For example, collegiate athletes with musculoskeletal injuries performed just as poorly on computerized neuropsychological tests as athletes with concussions.[177]
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.[178] 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. One study of 148 patients with mild head injury based on the GCS discovered that after 1 year, 26% had moderate disability and 3% had severe disability, but all these patients also had either radiological abnormalities or focal neurological signs, placing them in the more severe range of mild head injuries.[179] A recent review sponsored by the National Institute of Medicine concluded that there is no clear evidence of lasting cognitive impairments attributable to mild closed head injuries.[180]
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.[181, 182] In addition, return to play is contingent on the resolution of the initial concussion symptoms.[168]
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.[183] Other researchers more recently have stressed the prolonged nature of recovery from athletic head injuries and the need for longer recuperation prior to return to play.[184] American football, male gender, and young age ranges are associated with this syndrome.[185]
Posttraumatic epilepsy
Posttraumatic seizures occur clinically in approximately 4% of patients with head injuries within the first week of the injury. Continuous EEG monitoring may disclose a higher incidence (22%).[101, 102]
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.[186]
Although focal EEG findings traditionally have not been predictive of late seizures, one study reported that a focal EEG 1 month after injury resulted in a 3.49-times higher risk of posttraumatic epilepsy.[187]
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.[188]
Posttraumatic headaches
Posttraumatic headaches are common and may occur in 30-90% of patients after a head injury.[189] The alterations in cations, catecholamines, and excitatory amino acids are similar in both migraine and head injury.[190]
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.[191]
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.[53]
Posttraumatic psychiatric disorders
Disorders of emotional functioning have been documented repeatedly after head injuries. A case-control study of 91 patients hospitalized with traumatic brain injury recorded a 33% incidence of major depression.[192] Depression has been associated with left frontal injuries. Using a questionnaire methodology, 56% of 774 head injured patients of all levels of severity exhibited depression 10 weeks after their injury.[193] 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.[194]
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 patients with head injuries compared with nonpsychotic control patients with head injuries.[195]
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.
A study of 216 patients hospitalized during 2003-2005 in Ireland found 97% of patients with mild head injury attained a good recovery as measured by the Glasgow Outcome Scale, while 82% of the patients with severe head injury were either vegetative or markedly disabled. After 1 year, 11% of the total patients were unable to work.[196]
Another contemporary study of 309 Italian patients with moderate head injury found that only 15% were vegetative or severely disabled after 6 months. Basal skull fractures, subarachnoid hemorrhages, coagulopathies, subdurals, and poor emergency room clinical status predicted these unfavorable outcomes.[68]
Conversely, in Germany only 82% of 67 patients with mild or moderate head injury experienced a good 1-year outcome, and only 73% were able to return to work. Subjective complaints persisted in a large minority, with more than one third of patients reporting drowsiness, fatigue, forgetfulness, poor concentration, and irritability.[197] 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.[198]
A five-year paid employment status study of 5683 moderate to severely head-injured patients found that not only did age and injury severity adversely affect stable employment, but so did lack of transportation and elevated anxiety levels. Only 27% attained stable 5-year employment.[199] Another study reported that 41% of 4927 moderate and severe head-injured patients attained full or part-time paid employment at year 5.[200]
Overall, patients with traumatic brain injury are 2.23 times more likely to die than their non-injured counterparts. Brain-injured patients' life expectancies are reduced by about 9 years.[201]
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. Furthermore, even after controlling for injury severity and GCS scores, a current study of head-injured elderly motor vehicle accident victims demonstrated more than 3 times the mortality compared with their younger counterparts.[202, 203] Similar results were recently documented in a study of severely head-injured elders from Norway with 72% attaining an unfavorable outcome, defined as inability to be independent when out of their home environment.[204]
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.[205]
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 eMedicineHealth's First Aid and Injuries Center, Brain and Nervous System Center, and Eye and Vision Center. Also, see eMedicineHealth's patient education articles Concussion, Dementia in Head Injury, and Black Eye.
David A Olson, MD, Clinical Neurologist, Dekalb Neurology Group, Decatur, Georgia
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Florian P Thomas, MD, PhD, MA, MS, Chair, Neuroscience Institute and Department of Neurology, Director, National MS Society Multiple Sclerosis Center and Hereditary Neuropathy Foundation Center of Excellence, Hackensack University Medical Center; Founding Chair and Professor, Department of Neurology, Hackensack Meridian School of Medicine at Seton Hall University; Professor Emeritus, Department of Neurology, St Louis University School of Medicine; Editor-in-Chief, Journal of Spinal Cord Medicine
Disclosure: Nothing to disclose.
Chief Editor
Stephen A Berman, MD, PhD, MBA, Professor of Neurology, University of Central Florida College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Joseph Carcione, Jr, DO, MBA, Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans
Disclosure: Nothing to disclose.
References
Rates of TBI-related Emergency Department Visits, Hospitalizations, and Deaths--United States, 2001-2010. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/traumaticbraininjury/data/rates.html. Accessed: September 11, 2016.
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.
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.
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.
Melville, N. A. Progesterone Fails in Traumatic Brain Injury. Medscape Medical News. Available at http://www.medscape.com/viewarticle/836443. December 11, 2014; Accessed: December 11, 2014.
Carney N, Totten AM, O'Reilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Brain Trauma Foundation. Available at https://braintrauma.org/coma/guidelines. September 2016; Accessed: September 22, 2016.
Updated Mild Traumatic Brain Injury Guideline for Adults. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/traumaticbraininjury/mtbi_guideline.html. January 22, 2016; Accessed: September 24, 2016.
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.
Anderson P. Hemodynamic Complications Common in Traumatic Brain Injury. Available at http://www.medscape.com/viewarticle/778999. Accessed: March 25, 2013.
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.
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.
This 50-year-old woman with epilepsy seized and struck her head. Her initial Glasgow Coma Scale score was 12. Her scan shows prominent right temporal bleeding. She recovered to baseline without surgery.
This 50-year-old woman with epilepsy seized and struck her head. Her initial Glasgow Coma Scale score was 12. Her scan shows prominent right temporal bleeding. She recovered to baseline without surgery.
This 40-year-old woman was anticoagulated with warfarin (Coumadin) and fell out of her hospital bed. She subsequently died. Her CT scan shows an obvious right subdural hematoma with mass effect.
This 35-year-old man was in a motor vehicle accident. His initial Glasgow Coma Scale score was 7. He had left hemiparesis. He recovered orientation to temporal parameters after 1 week, but he remained disinhibited and hemiparetic (although able to ambulate). His MRI shows a diffusion-weighted hyperintensity in the right posterior internal capsular limb. This was attributed to an axonal injury. (An embolic workup for stroke was unremarkable, and no dissection was discerned on a carotid Doppler study.)
This 50-year-old woman with epilepsy seized and struck her head. Her initial Glasgow Coma Scale score was 12. Her scan shows prominent right temporal bleeding. She recovered to baseline without surgery.
This 50-year-old man was struck in the head in an assault. His scan shows a right acute subdural hematoma with no mass effect. His initial Glasgow Coma Scale score was 15. He returned home without major sequelae after 5 days of hospitalization.
This is a superior view of the CT scan shown in the previous image. This demonstrates a small left frontal intracranial contusion with some surrounding edema. This could be a marker of axonal injury.
This 23-year-old woman was in a motor vehicle accident with impact on the left. Her initial Glasgow Coma Scale score was 6 and she required intubation. Her scan shows a subtle right posterior frontal linear hyperdensity, most likely a small petechial bleed (contrecoup). This could also be a marker of axonal injury.
This 35-year-old man was in a motor vehicle accident. His initial Glasgow Coma Scale score was 7. He had left hemiparesis. He recovered orientation to temporal parameters after 1 week, but he remained disinhibited and hemiparetic (although able to ambulate). His MRI shows a diffusion-weighted hyperintensity in the right posterior internal capsular limb. This was attributed to an axonal injury. (An embolic workup for stroke was unremarkable, and no dissection was discerned on a carotid Doppler study.)
This 40-year-old woman was anticoagulated with warfarin (Coumadin) and fell out of her hospital bed. She subsequently died. Her CT scan shows an obvious right subdural hematoma with mass effect.
This elderly woman had a history of frequent falls and presented with seizures, possibly from her right hypodense subdural hematoma shown here. The subdural hematoma appears chronic and exhibits no mass effect.
This 23-year-old freelance graphic artist has drifted from job to job following his head injury 2 years prior to this scan. He was hospitalized initially for about 1 week for intracranial bleeding. This CT scan shows obvious medial bifrontal atrophy.
){kind=link}
){kind=link}
){kind=link}