Official reprint from UpToDate

www.uptodate.com 2014 UpToDate

Concussion and mild traumatic brain injury

Author Section Editors Deputy Editor

Randolph W Evans, MD, FAAN Michael J Aminoff, MD, DSc Janet L Wilterdink, MD
Maria E Moreira, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2014. | This topic last updated: Jul 03, 2013.

INTRODUCTION Mild traumatic brain injury (TBI) is common and, while typically benign, has a risk of serious short and
long-term sequelae. As a result, it is one of the most important public health problems.

Important considerations in the management of mild TBI include [1]:

Identification of immediate neurologic emergencies

Recognition and management of neurologic sequelae
Prevention of cumulative and chronic brain injury

An overview of the clinical presentation, evaluation, and management of mild TBI in adults is presented here. The
epidemiology, classification of TBI, severe traumatic TBI, postconcussion syndrome are discussed separately. Traumatic
brain injury in children is also discussed separately.

(See "Traumatic brain injury: Epidemiology, classification, and pathophysiology".)

(See "Management of acute severe traumatic brain injury".)
(See "Postconcussion syndrome".)
(See "Minor head trauma in infants and children: Evaluation".)
(See "Initial approach to severe traumatic brain injury in children".)

DEFINITIONS Mild traumatic brain injury (TBI) occurs with head injury due to contact and/or acceleration/deceleration
forces. It is typically defined as mild by a Glasgow Coma Scale (GCS) score of 13 to 15, measured at approximately 30
minutes after the injury (table 1). Some recommend classifying patients with a GCS score of 13 as moderate head injury
(GCS score of 9 to 12) because they seem more similar with regard to prognosis and incidence of intracranial
abnormalities [2-5].

The term concussion is often used in the medical literature as a synonym for mild TBI, but it probably describes a subset of
milder brain injury. The Quality Standards Subcommittee of the American Academy of Neurology defines concussion as a
trauma-induced alteration in mental status that may or may not involve loss of consciousness [1].

An international multidisciplinary conference on concussion convened in 2012 and affirmed the following definition [6]:
"Concussion is a brain injury and is defined as a complex pathophysiological process affecting the brain, induced by
traumatic biomechanical forces. Several common features that incorporate clinical, pathological, and biomechanical injury
constructs that may be utilized in defining the nature of a concussive head injury include the following:

Concussion may be caused by a direct blow to the head, face, neck, or elsewhere on the body with an 'impulsive'
force transmitted to the head.

Concussion typically results in the rapid onset of short-lived impairment of neurologic function that resolves
spontaneously. However, in some cases, symptoms and signs may evolve over a number of minutes to hours.

Concussion may result in neuropathological changes, but the acute clinical symptoms largely reflect a functional
disturbance rather than structural injury, and as such, no abnormality is seen on standard structural neuroimaging
studies.

Concussion results in a graded set of clinical syndromes that may or may not involve loss of consciousness.
Resolution of the clinical and cognitive symptoms typically follows a sequential course. However, it is important to
note that in some cases, symptoms may be prolonged.

EPIDEMIOLOGY Approximately 1.74 million people sustain a traumatic brain injury (TBI) in the United States every

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 year [7]. Most, 75 to 95 percent, are mild [8,9]. The annual incidence of mild head injury per 100,000 population has been
estimated to be 131 for San Diego County, California [10], 149 for Olmsted County, Minnesota [11] and 749 for Auckland,
New Zealand [12]. However, the incidence of mild head injury may be significantly higher, as many cases go unreported
[13,14].

For an industrialized country such as the United States, estimates of the relative causes of TBI are as follows: motor
vehicle accidents (20 to 45 percent), falls (30 to 38 percent), occupational accidents (10 percent), recreational accidents
(10 percent), and assaults (5 to 17 percent) [12,15]. In the elderly, falls are more likely the cause, and motor vehicle
accidents are more common in the young.

Mild TBI also occurs in contact sports; American football, ice hockey, soccer, boxing, and rugby have a particularly high
incidence [16]. The annual incidence of sports-related concussion in the United States is 1.6 to 3.8 million, and the
likelihood of an athlete in a contact sport experiencing a concussion is as high as 20 percent per season [17]. In football
alone, an estimated 10 percent of US college and 20 percent of US high school players sustain brain injuries each season
[18-20].

Mild TBI is also a common injury among soldiers who have participated in combat [14]. In a survey of 2525 Army infantry
soldiers performed three to four months after their return from a one-year deployment in Iraq, 5 percent reported injuries
with loss of consciousness and 10 percent reported injuries with altered consciousness [21]. The mechanisms of injury (in
order of frequency) included blasts or explosions, falls, motor vehicle accidents, and fragment, shrapnel, and bullet
wounds.

Males are more commonly head-injured, with a ratio between 2.0:1 and 2.8:1 [9,12]. However, this likely reflects the
greater participation of men in high risk activities that lead to TBI. Some data suggest that the concussion risk is greater for
female soccer and basketball players [19,22]. About one-half of all patients with mild TBI are between the ages of 15 and
34. Patients at moderate risk include those less than 5 years and those over 60 years. Lower socioeconomic status, lower
cognitive function, and a history of hospital admissions for intoxications are also risk factors for head injury [9,23].

PATHOPHYSIOLOGY Mild head injury may result in cortical contusions due to coup and contrecoup injuries [24]. While
axonal rupture from shear and tensile forces can occur at the time of severe head injury, milder degrees of axonal damage
are postulated to play a role in mild traumatic brain injury (TBI). Disruption of axonal neurofilament organization impairs
axonal transport leading to axonal swelling, Wallerian degeneration, and transection [25]. Release of excitatory
neurotransmitters acetylcholine, glutamate, and aspartate, and the generation of free radicals may contribute to secondary
injury [26]. One, somewhat controversial, theory regarding blast trauma is that the transfer of kinetic energy through the
vascular system to the brain can lead to TBI in the absence of a direct head injury [27].

That these processes occur in mild TBI is supported by findings in animal models of brain injury [25,28]. Evidence of
microscopic axonal injury, axon retraction bulbs and microglial clusters, have also been described in the pathological
examination of patients with minor head injury who died of other injuries [29,30]. Diffusion tensor MRI studies in patients
with mild TBI demonstrate increased fractional anisotropy and decreased diffusivity in the corpus callosum and other white
matter tracts that is suggestive of cytotoxic edema [31-33]. Other neuroimaging studies have shown that patients with mild
head injury may have more frequent and more extensive areas of abnormality as measured by SPECT, PET, CT perfusion,
and functional MRI than can be seen on a conventional CT scan, supporting a role for diffuse structural and/or physiologic
derangement in mild TBI [34-40].

CLINICAL FEATURES

Acute symptoms and signs The hallmark symptoms of concussion are confusion and amnesia, sometimes with, but
often without, preceding loss of consciousness [1,41]. These symptoms may be apparent immediately after the head injury
or may appear several minutes later [42]. It is important to emphasize that the alteration in mental status characteristic of
concussion can occur without loss of consciousness. In fact, the majority of concussions in sports occur without loss of
consciousness and are often unrecognized [43].

The amnesia almost always involves loss of memory for the traumatic event but frequently includes loss of recall for
events immediately before (retrograde amnesia) and after (anterograde amnesia) the head trauma. An athlete with
amnesia may be unable to recall details about recent plays in the game or details of well known current events in the
news. Amnesia also may be evidenced by the patient repeatedly asking a question that has already been answered.
Details regarding the presence and the duration of loss of consciousness, confusion, and amnesia are considered
potentially important to understanding the severity of the injury and the risk of subsequent complications. (See 'Second
impact syndrome' below.)

Other signs and symptoms of a concussion may immediately follow the head trauma or evolve gradually over several
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 minutes to hours. Early symptoms of concussion (within minutes to hours) include headache, dizziness (vertigo or
imbalance), lack of awareness of surroundings, and nausea and vomiting [42]. Over the next hours and days, patients may
also complain of mood and cognitive disturbances, sensitivity to light and noise, and sleep disturbances [44].

Many concussions occur without observed findings [41]. Signs observed in someone with a concussion may include the
following [42]:

Vacant stare (befuddled facial expression)

Delayed verbal expression (slower to answer questions or follow instructions)
Inability to focus attention (easily distracted and unable to follow through with normal activities)
Disorientation (walking in the wrong direction, unaware of time, date, place)
Slurred or incoherent speech (making disjointed or incomprehensible statements)
Gross observable incoordination (stumbling, inability to walk tandem/straight line)
Emotionality out of proportion to circumstances (appearing distraught, crying for no apparent reason)
Memory deficits (exhibited by patient repeatedly asking the same question that has already been answered or
inability to memorize and return three of three words and three of three objects for five minutes)
Any period of loss of consciousness (coma, unresponsiveness to stimuli)

Occasionally, associated transient cortical neurologic deficits, such as global amnesia or cortical blindness, can occur.
These deficits are thought to be secondary to vascular hyperreactivity and may be trauma-induced, migraine-equivalent
phenomena [45-47].

Seizures Early post-traumatic seizures are those that occur within the first week after head injury. These seizures are
considered to be acute symptomatic events and not epilepsy. Post-traumatic seizures occur in fewer than 5 percent of mild
or moderate traumatic brain injury (TBI), and they are more common with more severe TBI, especially if complicated by
intracranial hematoma [48,49].

About half occur within the first 24 hours of the injury; one quarter occur within the first hour [49,50]. The earlier a seizure
begins, the more likely it will be generalized in onset; after the first hour more than half are either simple partial (pure
motor) seizures or focal with secondary generalization [48,49]. Complex partial seizures are rare in this setting.

Early seizures increase the risk of post-traumatic epilepsy by fourfold, to more than 25 percent [49]. While anticonvulsants
may be used in the treatment of early seizures, they are not helpful in the prevention of post-traumatic epilepsy. (See
"Post-traumatic seizures and epilepsy".)

Complicated concussion With uncomplicated, mild TBI, limited structural axonal injury may be present but not evident
on diagnostic computed tomographic (CT) scanning or magnetic resonance imaging (MRI). However, mild TBI can be
complicated by coexistent cortical contusions and the development of intracranial hemorrhage.

Brain contusions are areas of bruising with associated localized ischemia, edema, and mass effect [51]. They result from
direct external contact forces or from the brain being slapped against intracranial surfaces with acceleration/deceleration
trauma. Signs of cortical contusions vary based on their number, size, and location within the brain but include focal
neurologic signs as well as confusion and impaired consciousness. Brain contusions may delay recovery from a
concussion.

Neurologic deterioration after mild TBI is highly suggestive of an evolving intracranial hematoma, which may be
intracerebral or sub- or epidural and usually occurs secondary to a tear in an intracranial artery or vein [52]. Signs include
worsening headache, focal neurologic signs, confusion, and lethargy, which may progress to loss of consciousness or
even death.

Subdural hemorrhage occurs when trauma results in the tearing of bridging veins or dura. The presentation may be acute,
subacute, or chronic. Epidural or intracerebral hemorrhage is usually arterial in origin and has an acute, abrupt
presentation, which might be delayed by minutes to hours from the original injury. It is estimated that before neurologic
deterioration, 20 to 50 percent of persons with epidural hemorrhage have a "lucid interval" following a brief loss of
consciousness or period of confusion. In the setting of substantive secondary hemorrhage with deterioration in the GCS,
the TBI would be reclassified as moderate or severe.

In addition to brain concussion, head trauma may result in injuries to other parts of the head or neck, including skull or
facial bone fractures, spine or spinal cord injuries, eye injuries, and damage to major blood vessels within the neck. A skull
fracture may be accompanied by underlying pathologic findings, including brain contusions, dural tears, and vascular
trauma [53].

ACUTE EVALUATION AND MANAGEMENT Patients suspected to have had a concussion or mild traumatic brain
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 injury (TBI) should be medically evaluated by a trained licensed health professional, whether in a doctors office,
emergency room, or on an athletic field sideline.

The acute evaluation of an individual includes a neurologic assessment and mental status testing [54]. Prolonged
unconsciousness, persistent mental status alterations, or abnormalities on neurologic examination require urgent
neuroimaging and neurosurgical consultation [1].

Cognitive assessment Mild TBI and concussion may be unrecognized by both the injured and non-medically-trained
observers, particularly if there is no loss of consciousness [41]. Simple questions of orientation have inadequate sensitivity
to detect mild TBI after head injury [55]. Some surveys have found that more than 80 percent of individuals with a past
concussion did not recognize it as such [56,57]. A number of diagnostic tools have been developed to aid in concussion-
recognition; however, none of these substitute for a more thorough medical evaluation, nor are they intended to be able to
rule out concussion [58].

Standardized examinations

Standardized Assessment of Concussion The Standardized Assessment of Concussion (SAC) was developed
as a standardized tool for the sideline evaluation of athletes who suffer a head injury [1,55]. The SAC includes
measures of orientation, immediate memory, concentration, delayed recall, neurologic screening, and exertional
maneuvers (table 2). Although not part of the scored assessment, the SAC also includes a graded symptom
checklist, a brief neurologic examination, and records the presence of post-traumatic and retrograde amnesia (table
3) [55,59].

Most studies evaluating the SAC have examined football players and compared scores after head injury to a
preinjury baseline score [55,59-64]. In this regard, it has an estimated sensitivity and specificity of 80 to 94 percent
and 76 to 91 percent, respectively [58].

The validity of this assessment in the absence of a baseline score is uncertain. Patients with concussion have
significantly lower scores than those without [55]. The SAC was also used as an evaluation tool in 165 children
(ages 6 to 18 years) who presented to an emergency room with concussion and were compared to a control group
with minor extremity injury, rather than to a premorbid baseline score as in the studies above [65]. SAC scores were
slightly lower in the concussion group, but this reached statistical significance only in the group age 12 to 14 years.
However, when the graded symptoms checklist (table 3) was summed, this score was significantly higher in
concussion patients compared to controls; with patients scoring a mean of 8 to 14 points, while controls scored 1 to
2 points.

The SAC should not be used in isolation to determine the readiness of athletes to return to play. (See 'Return to
play for athletes' below.)

Post-concussion Symptom Scale and Graded Symptom Checklist - Use of the Post-concussion symptom scale
and Graded symptom checklist requires the patient to rate severity of symptoms on a 7-point scale (0 = none; 6 =
severe) for 15 to 30 symptoms associated with concussion (eg, headache, dizziness, irritability, difficulty
concentrating). As with the SAC, a score greater than a baseline preinjury score is considered indicative of a
concussion, and has been found to have a sensitivity and specificity of 64 to 89 percent and 91 to 100 percent
respectively [58].

While not validated for diagnosis of concussion in the absence of a baseline score, reviewing such symptoms with a
patient who has not been assessed preinjury may still be useful to the clinician in determining the presence and
severity of a concussion.

Sport Concussion Assessment Tool 2 - Although not well validated, and the Sport Concussion Assessment Tool
2 (SCAT2) was endorsed by a Consensus Statement on Concussion in sport in 2008 and is increasingly used [66].
SCAT2 provides a detailed clinical assessment that includes a review of subjective symptoms, the Glasgow coma
scale, the SAC cognitive assessment, and an evaluation of balance and coordination. Although scored on a point
scale of 0 to 100, normative data and a cut-off score have not been defined. As with other standardized assessment
discussed here, use of the tool to guide the examination may provide a useful approach to patient evaluation, even
in the absence of validated scoring [67].

Westmead post-traumatic amnesia scale -Two studies have demonstrated that a revised version of the
Westmead post-traumatic amnesia scale (WPTAS) is both simple to perform, taking less than one minute in the

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 emergency department setting, and correlates with the findings in more detailed neuropsychologic testing [68,69].
An incorrect response to any one question on the WPTAS is considered a positive test for cognitive impairment
after head injury:

What is your name?

What is the name of this place?
Why are you here?
What month are we in?
What year are we in?
In what town/suburb are you in?
How old are you?
What is your date of birth?
What time of day is it? (morning, afternoon, evening)
Three pictures are presented for subsequent recall

Other measures - Other standardized measures used to assess post-traumatic amnesia and other cognitive
neurologic deficits associated with mild TBI include the Immediate Postconcussion Assessment and Cognitive
Testing (ImPACT), the Galveston orientation and amnesia test, the Military Acute Concussion Evaluation (MACE),
and Balance Error Scoring System (BESS), but these have not been well validated [66,68,70-74].

Neuroimaging Neuroimaging, usually with CT, is recommended for a subset of patients with mild TBI. While
neuroimaging is usually normal in patients with a concussion or mild TBI, there is a defined incidence of abnormalities,
some of which are clinically important even indicating neurosurgical intervention. A systematic review of the literature
estimated a prevalence of CT scan abnormalities of 5 percent among patients presenting to a hospital with a GCS = 15
and 30 percent for those presenting with a GCS = 13 [75]. The incidence of abnormalities leading to neurosurgical
intervention is about 1 percent. (See 'Complicated concussion' above.)

Choice of test Brain CT is the test of choice for emergency department evaluation. Most clinically important and all
neurosurgical abnormalities are visible on CT [76]. MRI may have a more important role in the evaluation of patients with
persistent post-traumatic sequelae. (See 'Sequelae' below.)

Compared with CT scanning, MRI is more sensitive in showing small areas of contusion or petechial hemorrhage, axonal
injury, and small extra-axial hematomas [35,77-79]. In case series of patients with mild TBI, MRI abnormalities were
reported in 30 percent of cases with normal CT findings [35,80]. Most of these additional abnormalities were lesions
"consistent with axonal injury," but small contusions and subarachnoid hemorrhage have also been described. While some
nonspecific MR findings may be unrelated to TBI, and do not clearly correlate with TBI severity or outcome, the presence
of one or more brain contusions or foci of hemorrhagic axonal injury has been associated with poorer 3-month outcomes
(OR 4.5 and 3.2, respectively) [79].

Diffusion tensor MRI (DTI) may be more sensitive than conventional MRI for traumatic axonal injury [31,32,81,82]. One
study used DTI to examine 63 US military personnel who sustained uncomplicated mild TBI due to blast trauma (plus
another blast-related mechanism of injury such as being struck by a blunt object or injured in a fall or motor vehicle
accident) and had normal CT scans [81]. As compared with controls, subjects showed marked abnormalities in the middle
cerebellar peduncles, in cingulum bundles, and in the right orbitofrontal white matter, regions not affection in civilian
injuries, which are usually limited to corpus callosum and other white matter tracts [31,32]. When analyzed individually, 18
subjects had abnormal scans. Follow-up scans 6-12 months later showed evidence of evolving injuries [81]. In some
studies, abnormalities on DTI appeared to correlate with symptom-severity [31,83], and in another, seemed to predict
long-term cognitive impairments [84].

Selection of patients There is evidence that patients with mild TBI can be selected for CT scan based on clinical
criteria. Two such criteria, the Canadian CT head rule and the New Orleans criteria, have been developed and
prospectively validated. A conservative approach to selecting individuals for neuroimaging based on these criteria is
presented in the Algorithm (algorithm 1).

The Canadian CT head rule requires a head CT for patients with mild TBI and any one of the following:

GCS <15 two hours after injury

Suspected open or depressed skull fracture
Any sign of basilar skull fracture: hemotympanum, raccoon eyes (intraorbital bruising), Battle's sign (retroauricular
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 bruising), or cerebrospinal fluid leak, oto- or rhinorrhea
Two or more episodes of vomiting
65 years of age or older
Amnesia before impact of 30 or more minutes
Dangerous mechanism (pedestrian struck by motor vehicle, occupant ejected from motor vehicle, fall from 3 feet
or 5 stairs)

Patients with:

Neurologic deficit
Seizure
Presence of bleeding diathesis or oral anticoagulant use

were excluded in the population in which these criteria were originally developed and tested. Hence, the presence of any
of these is also an indication for head CT in this protocol.

The New Orleans criteria are similar and apply to patients with a GCS of 15 and require CT scanning if there is headache,
vomiting, age >60 years, drug or alcohol intoxication, persistent anterograde amnesia, or visible trauma above the clavicle.

Two studies have validated and compared these criteria within the same patient populations:

In an emergency department-based study of 2707 patients with mild TBI (GCS 13 to 15), both criteria had high
sensitivities (100 percent) for detecting neurosurgical and clinically important brain injury abnormalities [85]. The
Canadian CT head rule was significantly more specific resulting in lower CT rates (52.1 versus 88.0 percent).

Another study in 3181 patients with mild TBI presenting to Dutch university hospitals also demonstrated 100 percent
sensitivity for the detection of neurosurgical abnormalities [86]. In this study, the sensitivity for any intracranial
abnormality (including findings not considered clinically important in the previous study) was higher with the New
Orleans criteria (99.4 versus 87.2 percent), and the specificity was higher using the Canadian CT head rule (39.7
versus 3.0 percent).

A study of 1582 consecutive patients with mild TBI (GCS 13 to 15), reported a lower sensitivity of the New Orleans
criteria for predicting both clinically significant CT changes and neurosurgical intervention; however, the New
Orleans criteria were not meant to be applied to patients with a GCS < 15 and when such patients were excluded,
both tests had a similar sensitivity for predicting clinically significant CT changes (93 versus 85 percent) and
neurosurgical intervention (100 versus 96 percent) [87].

Other studies have confirmed the lower specificity of the New Orleans criteria compared to the Canadian CT head rule
[87,88]. This is likely in large part due inclusion of intoxication as a criteria for imaging in the New Orleans criteria. The
American College of Emergency Physicians has endorsed indications for neuroimaging that are concordant with the New
Orleans criteria [89,90]. A conservative approach to selecting individuals for neuroimaging based on these criteria is
presented (algorithm 1).

The risk factors outlined by these criteria for predicting clinically important CT scan abnormalities also apply to patients
who have suffered a mild head injury without concussion (no loss of consciousness or post-traumatic amnesia) [91]. While
the odds ratios for individual risk factors are similar, the overall incidence of abnormal CT scans is lower in this group, and
the sensitivity and specificity of these neuroimaging criteria in this group of patients have not been prospectively assessed.

In addition to diagnostic utility, CT scanning is helpful for prognostic purposes and for determining patient disposition as
discussed in the following section. Neurologically normal patients with a normal CT scan are at low risk for subsequent
neurologic deterioration [2,92,93]. In one study, for example, none of 542 patients admitted to the hospital with a "mild"
head injury and a normal initial CT scan showed subsequent deterioration, and none required surgery [2].

Observation and disposition A conservative approach to the initial approach and disposition of patients with mild TBI
is presented (algorithm 1) [8,75].

Observation is recommended for at least 24 hours after a mild TBI because of the risk of intracranial complications [92,94].

Hospital admission is recommended for patients at risk for immediate complications from head injury [2,53,95-97]. These
include patients with:

GCS <15
Abnormal CT scan: intracranial bleeding, cerebral edema

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 Seizures
Abnormal bleeding parameters from underlying bleeding diathesis or oral anticoagulation

While available neurosurgical service in the admitting hospital may be preferred, it may not be required particularly if the
CT scan is normal. Decisions regarding transfer to a hospital with neurosurgical service should be individualized. Most
patients with an abnormal CT scan should have a follow-up study within 24 hours regardless of clinical change [98,99].
Isolated subarachnoid hemorrhage may be an exception [100,101]. In one retrospective registry review, isolated
subarachnoid hemorrhage in patients with mild TBI (GCS 13) was associated with a benign neurological outcome in all
478 patients; only one developed bilateral subdural hematomas that subsequently required intervention [100].

Admission should also be considered if no responsible person is available at home to monitor the patient for progression of
symptoms. In such patients, a normal CT scan may obviate the need for admission and should be considered specifically
for this purpose, even if not otherwise indicated according to the criteria discussed above. In one study, 575 patients with
GCS = 15 were randomized to immediate CT scan versus in-hospital observation. Similar clinical outcomes were seen in
the two groups; CT scan was the more cost-effective strategy [93,102]. No patient with a normal immediate CT scan later
suffered neurologic complications. Another report also found that strategies of observation and monitoring versus more
liberal CT scans yielded similar clinical outcomes, but emphasized that the latter approach was associated with higher
average radiation exposures and CT scan charges [103].

Outpatient observation may be permitted for the patient whose neurologic condition is very unlikely to deteriorate. There is
substantial evidence that patients with a GCS = 15, normal examination and head CT, and no predisposition to bleeding do
not suffer subsequent neurologic deterioration [89,92,94,104].

The observer should be given explicit and understandable instructions on patient monitoring and how and when to seek
medical help [94]. The following warning signs should prompt the caregiver to seek immediate medical help:

Inability to awaken the patient

Severe or worsening headaches
Somnolence or confusion
Restlessness, unsteadiness, or seizures
Difficulties with vision
Vomiting, fever, or stiff neck
Urinary or bowel incontinence
Weakness or numbness involving any part of the body

These signs may indicate that intracranial bleeding or evolving cerebral edema associated with brain contusions is
occurring. If the patient's condition deteriorates during observation, a thorough neurologic examination should be
performed, and immediate brain CT scanning should be performed once the patient's condition has been stabilized [92].
Consultation with appropriate subspecialists should be obtained if a repeat brain CT scan indicates new intracranial
pathologic findings. In the absence of a clinical deterioration, repeat CT scanning is generally not indicated [105,106].

For patients with uncomplicated concussion a period of physical and cognitive rest is often recommended for at least 24
hours and pending resolution of symptoms; this is followed by a gradual return to work, school, and physical activity [6].
However, the benefit of such recommendations has not been evaluated [107]. Patients with prolonged symptoms may
benefit from re-evaluation and treatment [108]. (See "Postconcussion syndrome".)

Avoidance of activities that may place the patient at risk of subsequent concussion during the acute symptomatic period
seems sensible. Athletes should not return to play while symptomatic. (See 'Return to play for athletes' below.)

SEQUELAE The prognosis for complete recovery is good for an appropriately managed concussion [109,110].
Nonetheless, there are a variety of short and long-term sequelae that have important implications.

Second impact syndrome Diffuse cerebral swelling is a rare but generally fatal complication of mild head injury
[111-114]. The cause is hypothesized to be disordered cerebral autoregulation causing cerebrovascular congestion and
malignant cerebral edema with increased intracranial pressure [42,113,115,116]. The term "second impact syndrome" is
used when diffuse cerebral swelling occurs after a second concussion, while an athlete is still symptomatic from an earlier
concussion [117-121]. Some have suggested a similarity with this phenomenon and the shaken baby syndrome [116].

The second impact syndrome is a rare and somewhat controversial complication [122-124]. It is unclear why this is not a
more frequently reported occurrence in boxers who seem at very high risk for repeated concussions within a short time
span. A 1998 review of the 17 published cases to date revealed that in 12 of these cases, there was insufficient
documentation of a second impact and/or cerebral pathology such that the diagnosis of second impact syndrome seemed

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 questionable [122]. According to a 2013 systematic review, no risk factors for this complication could be identified with any
certainty [58].

Postconcussion syndrome Postconcussion symptoms may result from brain injury or from trauma involving head and
neck structures [110]. These include headache, dizziness (including vertigo and nonspecific dizziness), neuropsychiatric
symptoms, and cognitive impairment [125]. These typically develop in the first days after mild traumatic brain injury (TBI)
and generally resolve within a few weeks to a few months. (See "Postconcussion syndrome".)

Post-traumatic headaches Headaches occur in 25 to 78 of patients after mild TBI [126-129]. According to the
International Headache Society (IHS) criteria, the onset of the post-traumatic headaches should be within seven days after
the injury [130]. The seven-day onset is arbitrary; some suggest that three months seems a more reasonable latency for
onset than does seven days [131]. Headaches may represent a specific injury to the head or neck, may be nonspecific in
character, and may have a symptom pattern indistinguishable from other nontraumatic headache syndromes such as
migraine and tension headache. A number of other explanations for persistent headaches have been advanced including
psychogenic, psychosocial, sociocultural, base rate misattribution, chronic pain, compensation and litigation, and
malingering [132]. (See "Postconcussion syndrome", section on 'Headaches'.)

Post-traumatic epilepsy Mild TBI is associated with a twofold increase in the risk of epilepsy for the first five years
after injury [133]. Seizures occurring within the first week of injury are acute symptomatic events and are not considered
epilepsy. Half of the seizures consistent with post-traumatic epilepsy will occur in the first year; 80 percent will occur within
two years. Prophylactic treatment with anticonvulsants does not prevent post-traumatic epilepsy and is not recommended.
(See "Post-traumatic seizures and epilepsy".)

Post-traumatic vertigo The incidence of post-traumatic vertigo has not been well characterized in prospective studies.
Head injury may lead to vertigo by a variety of mechanisms [134,135]:

Direct injury to the cochlear and/or vestibular structures usually occurs in the setting of transverse fractures of the
temporal bone. Hemotympanum and sensorineural loss often occur. The symptoms are maximal at onset and
progressively improve in most patients over weeks and months due to CNS compensation.

Labyrinthine concussion may occur from blunt injury to the membranous labyrinth against the otic capsule. This also
produces acute onset of vertigo and ataxia, which are maximal at the time of symptom onset and improve over days
to months, usually somewhat quicker then with the more severe injury described above.

Benign paroxysmal positional vertigo (BPPV) occurs after head injury causes shearing and displacement of
otoconia, which then settle into one of the semi-circular canals, most often the posterior canal in this setting. BPPV
produces isolated paroxysms of positionally induced vertigo [136]. There may be a hiatus of weeks and even
months between the injury and the onset of BPPV. (See "Benign paroxysmal positional vertigo".)

Perilymphatic fistula occurs when trauma causes rupture of the oval or round window and presents with sudden
unilateral sensorineural hearing loss and acute, persistent, gradually diminishing vertigo and ataxia. (See
"Pathophysiology, etiology, and differential diagnosis of vertigo", section on 'Perilymphatic fistula'.)

Other potential causes of post-traumatic vertigo include post-traumatic Meniere syndrome, brainstem ischemia due
to vertebral artery dissection, epileptic vertigo, and migraine-related vertigo.

The postconcussion syndrome includes dizziness, which is often nonspecific in character but is sometimes
described as vertigo. (See "Postconcussion syndrome".) When a patient has profound vertigo, especially when
there is accompanying nystagmus, ataxia, hearing symptoms, or evidence of direct vestibular injury, consideration
of the specific vestibular pathologies mentioned previously is advised in order to appropriately manage the patient.

Post-traumatic vertigo and dizziness is a substantial contributor to disability after mild TBI [137-141]. While the approach to
the evaluation and management of vertigo in this setting is similar to patients who have not had head injury, evaluation and
management may be complicated by the fact that there may be more than one site and mechanism of vestibular injury in
the same patient. Some case series also indicate that the symptoms are somewhat more refractory to treatment than their
idiopathic counterparts, perhaps because of multiple contributing pathologic injuries [134,137,142]. The evaluation and
treatment of these and other cause of vertigo are discussed in more detail elsewhere. (See "Evaluation of the patient with
vertigo" and "Treatment of vertigo" and "Benign paroxysmal positional vertigo".)

Other cranial nerve injuries The risk of injury to other cranial nerves increases with the severity of brain injury, but
these can also occur in mild TBI with an incidence of 0.3 percent according to one case series [143]. The distribution is
similar to that for moderate or severe head injuries:
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 Anosmia and hyposmia, which are often reported by the patient as impaired taste as well as smell, occur following
injury to olfactory filaments as they enter the brain through the cribiform plate. While recovery occurs in about
one-third of patients, loss of smell is likely permanent if present one year after the injury [144]. (See "Anatomy and
etiology of taste and smell disorders".)

Diplopia may result from injury to cranial nerves III, IV, and VI. In the setting of mild TBI, injury to cranial nerve IV is
most common, followed by VI. Cranial nerve III is less commonly affected by mild TBI. (See "Overview of diplopia".)

Facial pain and occipital neuralgia may occur in association with mild TBI. The former usually occurs in the setting
of blunt force injury to the trigeminal nerve in the face, while occipital nerve injury may be indirect from a contiguous
musculoskeletal injury in the neck. (See "Overview of craniofacial pain".)

Chronic traumatic encephalopathy There is some evidence that repeated concussions can cause cumulative
neuropsychological deficits (ie, increasing severity and duration of mental status abnormalities after each separate
incident) [145-147]. In addition to cognitive impairment and neuropsychological symptoms (behavior, personality changes,
depression, and suicidality), parkinsonism and other speech and gait abnormalities are described [17,148-150].

Increasing reports of dementia among American National Football League players with a history of multiple concussions
have focused attention on this entity, which has been labeled chronic traumatic encephalopathy in this setting
[148,151-153]. One cohort study found that neurodegenerative disease-related mortality was three times higher in retired
National Football League players compared to the general US population; Alzheimer disease-related mortality was four
times higher [154]. Cumulative effects of repeated concussions have also been implicated in cognitive impairments among
college football players [43] and poorer neuropsychological functioning in amateur and professional soccer players
[155,156].

Chronic neurologic impairment has also long been recognized as a sequelae of boxing, and has been called dementia
pugilistica in this setting [157]. The incidence is approximately 20 percent in professional boxers, and is much lower,
perhaps negligible, in amateur boxers [158,159]. The number of professional bouts (typically greater than 20) appears to
be more important than the number of "knockouts" [160]. The total number and type of head blows, particularly if the angle
of impact or failure to stabilize the head results in rotational head movements, may be important as well, but it is difficult to
quantify.

Single as well as multiple combat-related blast injuries in military personnel have also been identified as a precursor to
chronic traumatic encephalopathy [161-164].

Advanced neuroimaging techniques (diffusion tensor imaging, MR spectroscopy) have demonstrated associated white
matter and other abnormalities in these patients; however, further studies are needed to define the sensitivity and
specificity of specific findings and patterns of findings [153,165].

A 2013 systematic review, primarily of observational data, attempted to define categories of athletes at particular risk of
chronic impairments [58]:

Patients with more prominent subjective complaints after concussion, in particular early posttraumatic headache,
fatigue/fogginess, early amnesia, dizziness, and disorientation are also those who are more likely to have persistent
neurocognitive deficits on objective testing and those who are likely to have a longer recovery from concussion.

Prior concussion and a previous history of headaches also appear to be a risk factor for more severe deficits and
longer recovery, according to that same systematic review. Most studies involving professional athletes have found
a relationship between sustained impairments and increasing concussion exposure, but data are insufficient to
make the same association in amateur athletes. A threshold of injury (number, severity) has not been established.

APOE e4 genotype and preexisting learning disability may also be risk factors.

Age and gender have an undetermined role in predicting risk.

Neuropathologic studies in football players and boxers with this syndrome have demonstrated cerebral atrophy and a
fenestrated cavum septum pellucidum, with extensive tau-immunoreactive degenerative changes that are distinct from
other tauopathies (such as Alzheimer disease, AD) in their distribution with preferential involvement of the superficial
cortical layers [17,114,164,166-168]. A pathologic study in 85 patients found that the severity of pathologic findings could
be correlated with the severity of clinical findings [164].

APOE genotype may be a risk factor for chronic traumatic encephalopathy as it is for AD. In one series of 30 boxers,

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 APOE genotype was associated with severity of neurologic deficits among high, but not low, exposure boxers [169]. In a
similar study of 53 professional football players, older patients with APOE genotype were more likely to have cognitive
impairment than those without the APOE genotype [170]. However, other studies suggest that APOE epsilon 4 is not
associated with increased burden of neuropsychological deficits after TBI [171,172]. It has been suggested that recurrent
brain injury, and perhaps single brain injuries as well, may activate pathologic mechanisms similar to those that cause
brain degeneration in AD [173-175]. Some investigations suggest that trauma may incite a chronic neuroinflammatory
response, a mechanism which has also been implicated in AD [176]. However, further investigation is required; similarities
and associations between these two entities may reflect a co-incidence of the two conditions rather than a causal
relationship or shared pathogenesis [170].

In a neuropathological autopsy study of 12 former athletes with chronic traumatic encephalopathy (confirmed
pathologically), three also had motor neuron disease [177]. These three, along with seven others, were found to have
abundant TDP-43positive inclusions and neurites in the spinal cord as well. Although there has long been suspicion of
head trauma including trauma sustained in sports such as American football and soccer as a risk factor for motor neuron
disease [178], this is the first pathological evidence that supports this concern. Another report documented an excess
incidence of amyotrophic lateral sclerosis in Gulf War veterans, but did not specifically associate that finding with head
injuries [179]. Among patients with combined chronic traumatic encephalopathy and motor neuron disease, presenting
clinical features are usually motor weakness, atrophy, and fasciculations, with cognitive and behavioral abnormalities
appearing later [164].

Mortality At least one cohort study that included patients with mild TBI found that patients had increased mortality rates
compared with controls for at least 13 years after mild TBI (27.9 versus 13.2 per 1000 per year) [180]. All patients were
hospitalized after head injury, perhaps selecting for a more severely injured population. While comorbid lifestyle factors
(physical disability, living alone, alcohol abuse) further increased mortality in this group, the causes of death were similar
among head injured patients and controls. Another study in older adults, age >65 years found that recent TBI was
associated with increased mortality (HR = 2.1) [181].

RETURN TO PLAY FOR ATHLETES The concern that recurrent concussion(s) may lead to serious sequelae such as
second impact syndrome and dementia has led to the development of a series of guidelines that address concussion
severity and return to play for athletes [118,182]. These include the 2012 Consensus Statement on Concussion in Sport
[6], the American Academy of Neurology 2013 systematic review and evidence-based guideline [58], and the 2013
American Medical Society for Sports Medicine position statement [183]. However, there is a paucity of prospective data on
which to base recommendations, and current guidelines are largely consensus rather than evidence-based.

It is likely that premature return to play, when an athlete is still symptomatic, places that athlete at great risk for subsequent
injury, including recurrent concussion. In one prospective cohort study of 2905 college football players, 1 in 15 players with
concussion had additional concussions in the same season, most occurring 7 to 10 days after the first concussion [184].
With each concussion, the risk of future concussions increased. Individuals with three concussions had a three times
greater risk of future concussion compared with those without concussion. Another important consideration is the fact that
premature return to play by a symptomatic athlete places that athlete at greater risk for subsequent concussion and
potentially for cumulative brain injury [42,43,145]. (See 'Chronic traumatic encephalopathy' above.)

Based on these concerns, it is recommended that

Athletes suspected of having a concussion should be removed from play and evaluated by a licensed health
professional. An emergency department evaluation is indicated for any athlete who suffers loss of consciousness
[1,185]. (See 'Acute evaluation and management' above.)

Athletes with diagnosed concussion should be removed from play or practice (contact-risk activity) until symptoms
have resolved off medication.

A more conservative approach is probably appropriate for children and adolescents. (See "Minor head trauma in
infants and children: Evaluation".)

Individuals with a history of multiple concussions should undergo a more detailed evaluation regarding
neurobehavioral symptoms; if these are present, they should be referred for neurologic and neuropsychological
assessments [186]. Patients with persistent neurobehavioral complaints or objective deficits should be counseled
about the risk of chronic traumatic encephalopathy and possible retirement from contact sports.

The most recently issued 2012 Consensus Statement on Concussion in Sport was written by a multi-disciplinary,
international group and proposes a six-day graduated return to play protocol in which the athlete makes a stepwise

10 of 24
 increase in functional activity, is evaluated for symptoms, and is allowed to progress to the next stage each successive day
if asymptomatic (table 4) [6]. If symptoms occur, then the patient should drop back to the previous asymptomatic level and
reattempt progression after 24 hours. While these guidelines further suggest that a more rapid return to play may be
possible for asymptomatic adult athletes, same day return to play is not recommended. They also suggest that a more
conservative approach be followed for adolescents and children [187]. (See "Minor head trauma in infants and children:
Evaluation" and "The preparticipation sports examination in children and adolescents", section on 'Conditions that require
a treatment plan before or during exercise'.)

PREVENTION These combined acute and chronic morbidity associated with mild TBI suggest placing a premium on
reducing the number of concussions. Individuals, particularly older patients, who have had one head injury are at
increased risk of recurrent head injury [181].

Use of sport-specific helmets has been found to reduce head injuries in sports such as baseball, ice hockey, rugby, and
alpine skiing and snowboarding [188-191]. However, these case control studies leave open the possibility that the
observed effects associated with voluntary use of a helmet are the result of general risk avoidant behavior rather than the
helmet itself. In contrast, helmets have not been found to reduce the rate of head injury in soccer players [192].
Furthermore, in some cases, use of protective equipment may adversely affect playing behavior, encouraging risky
behavior, so that the risk of injury actually increases [193,194]. While American football helmets are widely used, there is
no standard for helmet construction to prevent concussions [195].

Bicycle and motorcycle helmets reduce the severity of accident-related head injuries. (See "Bicycle injuries in children:
Prevention".)

The NFL has made changes to rules, emphasizing player safety. As an example, in 2009, the return to play from
concussion guideline was amended and blows to the head of a defenseless receiver were prohibited. During the 2010 NFL
season, there was increased discipline (increased enforcement, large fines, and possible suspensions) for helmet to
helmet contact in violation of players safety rules and a change where the ball is immediately blown dead if a ball-carriers
helmet comes off during a play.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond
the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and
they answer the four or five key questions a patient might have about a given condition. These articles are best for patients
who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are
best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to
your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the
keyword(s) of interest.)

Basics topics (see "Patient information: Concussion in adults (The Basics)" and "Patient information: Skull and facial
fractures (The Basics)" and "Patient information: Closed head injury (The Basics)")

Beyond the Basics topics (see "Patient information: Head injury in children and adolescents (Beyond the Basics)"
and "Patient information: Dizziness and vertigo (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS Mild traumatic brain injury (TBI) is common; most individuals have an
excellent prognosis. However, some patients will have acute, life-threatening sequelae that require emergent evaluation
and management. Others will suffer chronic sequelae that are associated with mild to moderate disability. While the risks
of repeated concussions are not well defined, there is sufficient evidence to support measures that limit repeated injuries.

A mild TBI or concussion is an injury to the brain that may result after blunt force or an acceleration/deceleration
head injury. Its occurrence is most obvious when the individual has experienced brief loss of consciousness or
demonstrates overt confusion or amnesia. Subtler degrees of neurologic impairment are common and may be
unrecognized by the individual and observer. (See 'Definitions' above and 'Clinical features' above.)

An athlete with known or suspected head injury should be evaluated by a trained observer for potential concussion.
Simple orientation questions are inadequate to detect concussion. One suggested tool for nonmedically trained
personnel is the Standardized Assessment of Concussion (SAC) (table 2). (See 'Standardized examinations'
above.)

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 Patients with mild TBI should be medically evaluated. Patients who have suffered loss of consciousness or have
persistent symptoms should be referred to an emergency department. At risk patients should have a brain CT. A
conservative approach to the initial evaluation and disposition with mild TBI is presented (algorithm 1). (See 'Acute
evaluation and management' above.)

Repeated TBI soon after an initial injury may lead to acute life-threatening cerebral edema. Recurrent TBI may also
lead to chronic neuropsychological impairments. (See 'Second impact syndrome' above and 'Chronic traumatic
encephalopathy' above.)

Other sequelae of mild TBI can include postconcussion syndrome, headaches, epilepsy, and vertigo. (See
'Sequelae' above.)

We recommend that athletes NOT return to play the same day after concussion, and also that athletes NOT return
to play until asymptomatic off medication (Grade 1C). A more conservative approach is probably appropriate for
children and adolescents.

Individuals with a history of multiple concussions should undergo a more detailed evaluation regarding
neurobehavioral symptoms; if these are present, they should be referred for neurologic and neuropsychological
assessments. (See 'Return to play for athletes' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

1. Practice parameter: the management of concussion in sports (summary statement). Report of the Quality Standards
Subcommittee. Neurology 1997; 48:581.
2. Stein SC, Ross SE. The value of computed tomographic scans in patients with low-risk head injuries. Neurosurgery
1990; 26:638.
3. Servadei F, Teasdale G, Merry G, Neurotraumatology Committee of the World Federation of Neurosurgical Societies.
Defining acute mild head injury in adults: a proposal based on prognostic factors, diagnosis, and management. J
Neurotrauma 2001; 18:657.
4. Uchino Y, Okimura Y, Tanaka M, et al. Computed tomography and magnetic resonance imaging of mild head
injury--is it appropriate to classify patients with Glasgow Coma Scale score of 13 to 15 as "mild injury"? Acta
Neurochir (Wien) 2001; 143:1031.
5. Culotta VP, Sementilli ME, Gerold K, Watts CC. Clinicopathological heterogeneity in the classification of mild head
injury. Neurosurgery 1996; 38:245.
6. McCrory P, Meeuwisse WH, Aubry M, et al. Consensus statement on concussion in sport: the 4th International
Conference on Concussion in Sport held in Zurich, November 2012. Br J Sports Med 2013; 47:250.
7. Centers for Disease Control and Prevention. Injury Prevention & Control: Traumatic Brain Injury. Traumatic Brain
Injury. Available at: http://www.cdc.gov/TraumaticBrainInjury/index.html (Accessed on March 25, 2013).
8. Vos PE, Battistin L, Birbamer G, et al. EFNS guideline on mild traumatic brain injury: report of an EFNS task force.
Eur J Neurol 2002; 9:207.
9. Kraus JF, McArthur DL. Epidemiologic aspects of brain injury. Neurol Clin 1996; 14:435.
10. Kraus JF, Nourjah P. The epidemiology of mild, uncomplicated brain injury. J Trauma 1988; 28:1637.
11. Annegers JF, Grabow JD, Kurland LT, Laws ER Jr. The incidence, causes, and secular trends of head trauma in
Olmsted County, Minnesota, 1935-1974. Neurology 1980; 30:912.
12. Feigin VL, Theadom A, Barker-Collo S, et al. Incidence of traumatic brain injury in New Zealand: a population-based
study. Lancet Neurol 2013; 12:53.
13. Bernstein DM. Recovery from mild head injury. Brain Inj 1999; 13:151.
14. Xydakis MS, Ling GS, Mulligan LP, et al. Epidemiologic aspects of traumatic brain injury in acute combat casualties
at a major military medical center: a cohort study. Ann Neurol 2012; 72:673.
15. Jennett B, Frankovyski RF. The epidemiology of head injury. In: Handbook of Clinical Neurology, Braakman R (Ed),
Elsevier, New York 1990. Vol 13, p.1.
16. Guerriero RM, Proctor MR, Mannix R, Meehan WP 3rd. Epidemiology, trends, assessment and management of
sport-related concussion in United States high schools. Curr Opin Pediatr 2012; 24:696.

12 of 24
 17. McKee AC, Cantu RC, Nowinski CJ, et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after
repetitive head injury. J Neuropathol Exp Neurol 2009; 68:709.
18. Kelly JP, Rosenberg JH. The development of guidelines for the management of concussion in sports. J Head
Trauma Rehabil 1998; 13:53.
19. Powell JW, Barber-Foss KD. Traumatic brain injury in high school athletes. JAMA 1999; 282:958.
20. Marar M, McIlvain NM, Fields SK, Comstock RD. Epidemiology of concussions among United States high school
athletes in 20 sports. Am J Sports Med 2012; 40:747.
21. Hoge CW, McGurk D, Thomas JL, et al. Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med
2008; 358:453.
22. Lincoln AE, Caswell SV, Almquist JL, et al. Trends in concussion incidence in high school sports: a prospective
11-year study. Am J Sports Med 2011; 39:958.
23. Nordstrm A, Edin BB, Lindstrm S, Nordstrm P. Cognitive function and other risk factors for mild traumatic brain
injury in young men: nationwide cohort study. BMJ 2013; 346:f723.
24. Goodman JC. Pathologic changes in mild head injury. Semin Neurol 1994; 14:19.
25. Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head
Trauma Rehabil 2005; 20:76.
26. Hayes RL, Dixon CE. Neurochemical changes in mild head injury. Semin Neurol 1994; 14:25.
27. Bhattacharjee Y. Neuroscience. Shell shock revisited: solving the puzzle of blast trauma. Science 2008; 319:406.
28. Ommaya AK, Gennarelli TA. Cerebral concussion and traumatic unconsciousness. Correlation of experimental and
clinical observations of blunt head injuries. Brain 1974; 97:633.
29. Oppenheimer DR. Microscopic lesions in the brain following head injury. J Neurol Neurosurg Psychiatry 1968;
31:299.
30. Blumbergs PC, Scott G, Manavis J, et al. Staining of amyloid precursor protein to study axonal damage in mild head
injury. Lancet 1994; 344:1055.
31. Wilde EA, McCauley SR, Hunter JV, et al. Diffusion tensor imaging of acute mild traumatic brain injury in
adolescents. Neurology 2008; 70:948.
32. Mayer AR, Ling J, Mannell MV, et al. A prospective diffusion tensor imaging study in mild traumatic brain injury.
Neurology 2010; 74:643.
33. Aoki Y, Inokuchi R, Gunshin M, et al. Diffusion tensor imaging studies of mild traumatic brain injury: a meta-analysis.
J Neurol Neurosurg Psychiatry 2012; 83:870.
34. McAllister TW, Sparling MB, Flashman LA, Saykin AJ. Neuroimaging findings in mild traumatic brain injury. J Clin
Exp Neuropsychol 2001; 23:775.
35. Hughes DG, Jackson A, Mason DL, et al. Abnormalities on magnetic resonance imaging seen acutely following mild
traumatic brain injury: correlation with neuropsychological tests and delayed recovery. Neuroradiology 2004; 46:550.
36. Kant R, Smith-Seemiller L, Isaac G, Duffy J. Tc-HMPAO SPECT in persistent post-concussion syndrome after mild
head injury: comparison with MRI/CT. Brain Inj 1997; 11:115.
37. Korn A, Golan H, Melamed I, et al. Focal cortical dysfunction and blood-brain barrier disruption in patients with
Postconcussion syndrome. J Clin Neurophysiol 2005; 22:1.
38. Umile EM, Sandel ME, Alavi A, et al. Dynamic imaging in mild traumatic brain injury: support for the theory of medial
temporal vulnerability. Arch Phys Med Rehabil 2002; 83:1506.
39. Chen SH, Kareken DA, Fastenau PS, et al. A study of persistent post-concussion symptoms in mild head trauma
using positron emission tomography. J Neurol Neurosurg Psychiatry 2003; 74:326.
40. Metting Z, Rdiger LA, Stewart RE, et al. Perfusion computed tomography in the acute phase of mild head injury:
regional dysfunction and prognostic value. Ann Neurol 2009; 66:809.
41. Duhaime AC, Beckwith JG, Maerlender AC, et al. Spectrum of acute clinical characteristics of diagnosed
concussions in college athletes wearing instrumented helmets: clinical article. J Neurosurg 2012; 117:1092.
42. Kelly JP, Rosenberg JH. Diagnosis and management of concussion in sports. Neurology 1997; 48:575.
43. Collins MW, Grindel SH, Lovell MR, et al. Relationship between concussion and neuropsychological performance in
college football players. JAMA 1999; 282:964.
44. Cantu RC. Posttraumatic Retrograde and Anterograde Amnesia: Pathophysiology and Implications in Grading and
Safe Return to Play. J Athl Train 2001; 36:244.
45. Yamamoto LG, Bart RD Jr. Transient blindness following mild head trauma. Criteria for a benign outcome. Clin
Pediatr (Phila) 1988; 27:479.
46. Haas DC, Ross GS. Transient global amnesia triggered by mild head trauma. Brain 1986; 109 ( Pt 2):251.
13 of 24
 47. Harrison DW, Walls RM. Blindness following minor head trauma in children: a report of two cases with a review of
the literature. J Emerg Med 1990; 8:21.
48. Lee ST, Lui TN. Early seizures after mild closed head injury. J Neurosurg 1992; 76:435.
49. Barry E. Posttraumatic epilepsy, In: The treatment of epilepsy: Principles and practice, 3rd ed, Wyllie E (Ed),
Lippincott Williams, Philadelphia 2001. p.609.
50. Pagni CA. Posttraumatic epilepsy. Incidence and prophylaxis. Acta Neurochir Suppl (Wien) 1990; 50:38.
51. Williams DH, Levin HS, Eisenberg HM. Mild head injury classification. Neurosurgery 1990; 27:422.
52. Liau LM, Bergsneider M, Becker DP. Pathology and pathophysiology of head injury. In: Neurological surgery: A
comprehensive reference guide to the diagnosis and management of neurosurgical problems, 4th ed, Youmans JR,
Becker DP, et al (Eds), Saunders, Philadelphia 1996. p.1549.
53. Dacey RG Jr, Alves WM, Rimel RW, et al. Neurosurgical complications after apparently minor head injury.
Assessment of risk in a series of 610 patients. J Neurosurg 1986; 65:203.
54. McCrory P. Do not go gentle into that good night... Br J Sports Med 2005; 39:691.
55. McCrea M, Kelly JP, Kluge J, et al. Standardized assessment of concussion in football players. Neurology 1997;
48:586.
56. Delaney JS, Abuzeyad F, Correa JA, Foxford R. Recognition and characteristics of concussions in the emergency
department population. J Emerg Med 2005; 29:189.
57. Delaney SJ, Lacroix VJ, Leclerc S, et al. Concussions during the 1997 Canadian football league season. Clin J
Sports Med 2000; 54:1488.
58. Giza CC, Kutcher JS, Ashwal S, et al. Summary of evidence-based guideline update: evaluation and management of
concussion in sports: report of the Guideline Development Subcommittee of the American Academy of Neurology.
Neurology 2013; 80:2250.
59. McCrea M, Kelly JP, Randolph C, et al. Standardized assessment of concussion (SAC): on-site mental status
evaluation of the athlete. J Head Trauma Rehabil 1998; 13:27.
60. Barr WB, McCrea M. Sensitivity and specificity of standardized neurocognitive testing immediately following sports
concussion. J Int Neuropsychol Soc 2001; 7:693.
61. McCrea M, Guskiewicz KM, Marshall SW, et al. Acute effects and recovery time following concussion in collegiate
football players: the NCAA Concussion Study. JAMA 2003; 290:2556.
62. McCrea M. Standardized Mental Status Testing on the Sideline After Sport-Related Concussion. J Athl Train 2001;
36:274.
63. McCrea M, Barr WB, Guskiewicz K, et al. Standard regression-based methods for measuring recovery after sport-
related concussion. J Int Neuropsychol Soc 2005; 11:58.
64. Daniel JC, Nassiri JD, Wilckens J, Land BC. The implementation and use of the standardized assessment of
concussion at the U.S. Naval Academy. Mil Med 2002; 167:873.
65. Grubenhoff JA, Kirkwood M, Gao D, et al. Evaluation of the standardized assessment of concussion in a pediatric
emergency department. Pediatrics 2010; 126:688.
66. 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 2009; 19:185.
67. Guskiewicz KM, Register-Mihalik J, McCrory P, et al. Evidence-based approach to revising the SCAT2: introducing
the SCAT3. Br J Sports Med 2013; 47:289.
68. Shores EA, Lamml A, Hullick C, et al. The diagnostic accuracy of the Revised Westmead PTA Scale as an adjunct
to the Glasgow Coma Scale in the early identification of cognitive impairment in patients with mild traumatic brain
injury. J Neurol Neurosurg Psychiatry 2008; 79:1100.
69. Ponsford J, Willmott C, Rothwell A, et al. Use of the Westmead PTA scale to monitor recovery of memory after mild
head injury. Brain Inj 2004; 18:603.
70. Levin HS, O'Donnell VM, Grossman RG. The Galveston Orientation and Amnesia Test. A practical scale to assess
cognition after head injury. J Nerv Ment Dis 1979; 167:675.
71. Mayers LB, Redick TS. Clinical utility of ImPACT assessment for postconcussion return-to-play counseling:
psychometric issues. J Clin Exp Neuropsychol 2012; 34:235.
72. Elbin RJ, Schatz P, Covassin T. One-year test-retest reliability of the online version of ImPACT in high school
athletes. Am J Sports Med 2011; 39:2319.
73. Valovich McLeod TC, Bay RC, Lam KC, Chhabra A. Representative baseline values on the Sport Concussion
Assessment Tool 2 (SCAT2) in adolescent athletes vary by gender, grade, and concussion history. Am J Sports Med
2012; 40:927.
74. Schatz P, Sandel N. Sensitivity and specificity of the online version of ImPACT in high school and collegiate athletes.
14 of 24
 Am J Sports Med 2013; 41:321.
75. Borg J, Holm L, Cassidy JD, et al. Diagnostic procedures in mild traumatic brain injury: results of the WHO
Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med 2004; :61.
76. Manolakaki D, Velmahos GC, Spaniolas K, et al. Early magnetic resonance imaging is unnecessary in patients with
traumatic brain injury. J Trauma 2009; 66:1008.
77. Hesselink JR, Dowd CF, Healy ME, et al. MR imaging of brain contusions: a comparative study with CT. AJR Am J
Roentgenol 1988; 150:1133.
78. Wilberger JE Jr, Rothfus WE, Tabas J, et al. Acute tissue tear hemorrhages of the brain: computed tomography and
clinicopathological correlations. Neurosurgery 1990; 27:208.
79. Yuh EL, Mukherjee P, Lingsma HF, et al. Magnetic resonance imaging improves 3-month outcome prediction in mild
traumatic brain injury. Ann Neurol 2013; 73:224.
80. Mittl RL, Grossman RI, Hiehle JF, et al. Prevalence of MR evidence of diffuse axonal injury in patients with mild head
injury and normal head CT findings. AJNR Am J Neuroradiol 1994; 15:1583.
81. Mac Donald CL, Johnson AM, Cooper D, et al. Detection of blast-related traumatic brain injury in U.S. military
personnel. N Engl J Med 2011; 364:2091.
82. Brandstack N, Kurki T, Tenovuo O. Quantitative diffusion-tensor tractography of long association tracts in patients
with traumatic brain injury without associated findings at routine MR imaging. Radiology 2013; 267:231.
83. Virji-Babul N, Borich MR, Makan N, et al. Diffusion tensor imaging of sports-related concussion in adolescents.
Pediatr Neurol 2013; 48:24.
84. Gu L, Li J, Feng DF, et al. Detection of white matter lesions in the acute stage of diffuse axonal injury predicts
long-term cognitive impairments: a clinical diffusion tensor imaging study. J Trauma Acute Care Surg 2013; 74:242.
85. Stiell IG, Clement CM, Rowe BH, et al. Comparison of the Canadian CT Head Rule and the New Orleans Criteria in
patients with minor head injury. JAMA 2005; 294:1511.
86. Smits M, Dippel DW, de Haan GG, et al. External validation of the Canadian CT Head Rule and the New Orleans
Criteria for CT scanning in patients with minor head injury. JAMA 2005; 294:1519.
87. Bouida W, Marghli S, Souissi S, et al. Prediction value of the Canadian CT head rule and the New Orleans criteria
for positive head CT scan and acute neurosurgical procedures in minor head trauma: a multicenter external
validation study. Ann Emerg Med 2013; 61:521.
88. Papa L, Stiell IG, Clement CM, et al. Performance of the Canadian CT Head Rule and the New Orleans Criteria for
predicting any traumatic intracranial injury on computed tomography in a United States Level I trauma center. Acad
Emerg Med 2012; 19:2.
89. Jagoda AS, Bazarian JJ, Bruns JJ Jr, et al. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic
brain injury in the acute setting. Ann Emerg Med 2008; 52:714.
90. Centers for Disease Control and Prevention. Injury Prevention & Control: Traumatic Brain Injury. Heads Up to
Clinicians: Updated Mild Traumatic Brain Injury Guideline for Adults. http://www.cdc.gov/concussion/HeadsUp
/clinicians_guide.html (Accessed on October 23, 2010).
91. Smits M, Hunink MG, Nederkoorn PJ, et al. A history of loss of consciousness or post-traumatic amnesia in minor
head injury: "conditio sine qua non" or one of the risk factors? J Neurol Neurosurg Psychiatry 2007; 78:1359.
92. The management of minor closed head injury in children. Committee on Quality Improvement, American Academy of
Pediatrics. Commission on Clinical Policies and Research, American Academy of Family Physicians. Pediatrics
1999; 104:1407.
93. af Geijerstam JL, Oredsson S, Britton M, OCTOPUS Study Investigators. Medical outcome after immediate
computed tomography or admission for observation in patients with mild head injury: randomised controlled trial.
BMJ 2006; 333:465.
94. Lawler KA, Terregino CA. Guidelines for evaluation and education of adult patients with mild traumatic brain injuries
in an acute care hospital setting. J Head Trauma Rehabil 1996; 11:18.
95. Atzema C, Mower WR, Hoffman JR, et al. Defining "therapeutically inconsequential" head computed tomographic
findings in patients with blunt head trauma. Ann Emerg Med 2004; 44:47.
96. Nishijima DK, Offerman SR, Ballard DW, et al. Immediate and delayed traumatic intracranial hemorrhage in patients
with head trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med 2012; 59:460.
97. Menditto VG, Lucci M, Polonara S, et al. Management of minor head injury in patients receiving oral anticoagulant
therapy: a prospective study of a 24-hour observation protocol. Ann Emerg Med 2012; 59:451.
98. Bee TK, Magnotti LJ, Croce MA, et al. Necessity of repeat head CT and ICU monitoring in patients with minimal
brain injury. J Trauma 2009; 66:1015.
99. Thorson CM, Van Haren RM, Otero CA, et al. Repeat head computed tomography after minimal brain injury

15 of 24
 identifies the need for craniotomy in the absence of neurologic change. J Trauma Acute Care Surg 2013; 74:967.
100. Quigley MR, Chew BG, Swartz CE, Wilberger JE. The clinical significance of isolated traumatic subarachnoid
hemorrhage. J Trauma Acute Care Surg 2013; 74:581.
101. Borczuk P, Penn J, Peak D, Chang Y. Patients with traumatic subarachnoid hemorrhage are at low risk for
deterioration or neurosurgical intervention. J Trauma Acute Care Surg 2013; 74:1504.
102. Norlund A, Mark LA, af Geijerstam JL, et al. Immediate computed tomography or admission for observation after
mild head injury: cost comparison in randomised controlled trial. BMJ 2006; 333:469.
103. Mahoney E, Agarwal S, Li B, et al. Evidence-based guidelines are equivalent to a liberal computed tomography scan
protocol for initial patient evaluation but are associated with decreased computed tomography scan use, cost, and
radiation exposure. J Trauma Acute Care Surg 2012; 73:573.
104. Jagoda AS, Cantrill SV, Wears RL, et al. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic
brain injury in the acute setting. Ann Emerg Med 2002; 40:231.
105. Peck KA, Sise CB, Shackford SR, et al. Delayed intracranial hemorrhage after blunt trauma: are patients on preinjury
anticoagulants and prescription antiplatelet agents at risk? J Trauma 2011; 71:1600.
106. Sifri ZC, Nayak N, Homnick AT, et al. Utility of repeat head computed tomography in patients with an abnormal
neurologic examination after minimal head injury. J Trauma 2011; 71:1605.
107. Schneider KJ, Iverson GL, Emery CA, et al. The effects of rest and treatment following sport-related concussion: a
systematic review of the literature. Br J Sports Med 2013; 47:304.
108. Makdissi M, Cantu RC, Johnston KM, et al. The difficult concussion patient: what is the best approach to
investigation and management of persistent (>10 days) postconcussive symptoms? Br J Sports Med 2013; 47:308.
109. Evans, RW. The postconcussion syndrome and the sequelae of mild head injury. In: Neurology and Trauma, 2nd ed,
Evans, RW (Ed), Oxford, New York 2006. p.95.
110. Kushner D. Mild traumatic brain injury: toward understanding manifestations and treatment. Arch Intern Med 1998;
158:1617.
111. Bruce DA. Delayed deterioration of consciousness after trivial head injury in childhood. Br Med J (Clin Res Ed) 1984;
289:715.
112. Kors EE, Terwindt GM, Vermeulen FL, et al. Delayed cerebral edema and fatal coma after minor head trauma: role of
the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol 2001;
49:753.
113. Wetjen NM, Pichelmann MA, Atkinson JL. Second impact syndrome: concussion and second injury brain
complications. J Am Coll Surg 2010; 211:553.
114. Jordan BD. The clinical spectrum of sport-related traumatic brain injury. Nat Rev Neurol 2013; 9:222.
115. McQuillen JB, McQuillen EN, Morrow P. Trauma, sport, and malignant cerebral edema. Am J Forensic Med Pathol
1988; 9:12.
116. Cantu RC, Gean AD. Second-impact syndrome and a small subdural hematoma: an uncommon catastrophic result
of repetitive head injury with a characteristic imaging appearance. J Neurotrauma 2010; 27:1557.
117. Saunders RL, Harbaugh RE. The second impact in catastrophic contact-sports head trauma. JAMA 1984; 252:538.
118. Collins MW, Lovell MR, Mckeag DB. Current issues in managing sports-related concussion. JAMA 1999; 282:2283.
119. Cantu, RC, Voy, R. Second impact syndrome: a risk in any sport. Physician Sports Med 1995; 23:27.
120. Weinstein E, Turner M, Kuzma BB, Feuer H. Second impact syndrome in football: new imaging and insights into a
rare and devastating condition. J Neurosurg Pediatr 2013; 11:331.
121. Potts MA, Stewart EW, Griesser MJ, et al. Exceptional neurologic recovery in a teenage football player after second
impact syndrome with a thin subdural hematoma. PM R 2012; 4:530.
122. McCrory PR, Berkovic SF. Second impact syndrome. Neurology 1998; 50:677.
123. McCrory P. Does second impact syndrome exist? Clin J Sport Med 2001; 11:144.
124. McCrory P, Davis G, Makdissi M. Second impact syndrome or cerebral swelling after sporting head injury. Curr
Sports Med Rep 2012; 11:21.
125. Dikmen SS, Corrigan JD, Levin HS, et al. Cognitive outcome following traumatic brain injury. J Head Trauma Rehabil
2009; 24:430.
126. Paniak C, Reynolds S, Phillips K, et al. Patient complaints within 1 month of mild traumatic brain injury: a controlled
study. Arch Clin Neuropsychol 2002; 17:319.
127. Baandrup L, Jensen R. Chronic post-traumatic headache--a clinical analysis in relation to the International Headache
Classification 2nd Edition. Cephalalgia 2005; 25:132.
128. Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury: a systematic review. JAMA 2008;

16 of 24
 300:711.
129. Blume HK, Vavilala MS, Jaffe KM, et al. Headache after pediatric traumatic brain injury: a cohort study. Pediatrics
2012; 129:e31.
130. Headache Classification Subcommittee of the International Headache Society. The International Classification of
Headache Disorders, 2nd edition. Cephalalgia 2004; 24 Suppl 1:59.
131. Haas DC. Chronic post-traumatic headaches classified and compared with natural headaches. Cephalalgia 1996;
16:486.
132. Evans RW. Persistent post-traumatic headache, postconcussion syndrome, and whiplash injuries: the evidence for a
non-traumatic basis with an historical review. Headache 2010; 50:716.
133. Annegers JF, Grabow JD, Groover RV, et al. Seizures after head trauma: a population study. Neurology 1980;
30:683.
134. Friedman JM. Post-traumatic vertigo. Med Health R I 2004; 87:296.
135. Hoffer ME, Gottshall KR, Moore R, et al. Characterizing and treating dizziness after mild head trauma. Otol Neurotol
2004; 25:135.
136. Ahn SK, Jeon SY, Kim JP, et al. Clinical characteristics and treatment of benign paroxysmal positional vertigo after
traumatic brain injury. J Trauma 2011; 70:442.
137. Marzo SJ, Leonetti JP, Raffin MJ, Letarte P. Diagnosis and management of post-traumatic vertigo. Laryngoscope
2004; 114:1720.
138. Chamelian L, Feinstein A. Outcome after mild to moderate traumatic brain injury: the role of dizziness. Arch Phys
Med Rehabil 2004; 85:1662.
139. Yang CC, Tu YK, Hua MS, Huang SJ. The association between the postconcussion symptoms and clinical outcomes
for patients with mild traumatic brain injury. J Trauma 2007; 62:657.
140. De Kruijk JR, Leffers P, Menheere PP, et al. Prediction of post-traumatic complaints after mild traumatic brain injury:
early symptoms and biochemical markers. J Neurol Neurosurg Psychiatry 2002; 73:727.
141. Lau BC, Kontos AP, Collins MW, et al. Which on-field signs/symptoms predict protracted recovery from sport-related
concussion among high school football players? Am J Sports Med 2011; 39:2311.
142. Gordon CR, Levite R, Joffe V, Gadoth N. Is posttraumatic benign paroxysmal positional vertigo different from the
idiopathic form? Arch Neurol 2004; 61:1590.
143. Coello AF, Canals AG, Gonzalez JM, Martn JJ. Cranial nerve injury after minor head trauma. J Neurosurg 2010;
113:547.
144. Yousem DM, Geckle RJ, Bilker WB, et al. Posttraumatic olfactory dysfunction: MR and clinical evaluation. AJNR Am
J Neuroradiol 1996; 17:1171.
145. Gronwall D, Wrightson P. Cumulative effect of concussion. Lancet 1975; 2:995.
146. Covassin T, Elbin R, Kontos A, Larson E. Investigating baseline neurocognitive performance between male and
female athletes with a history of multiple concussion. J Neurol Neurosurg Psychiatry 2010; 81:597.
147. McAllister TW, Flashman LA, Maerlender A, et al. Cognitive effects of one season of head impacts in a cohort of
collegiate contact sport athletes. Neurology 2012; 78:1777.
148. Omalu BI, DeKosky ST, Hamilton RL, et al. Chronic traumatic encephalopathy in a national football league player:
part II. Neurosurgery 2006; 59:1086.
149. DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis
and biomarkers. Nat Rev Neurol 2013; 9:192.
150. Wang HK, Lin SH, Sung PS, et al. Population based study on patients with traumatic brain injury suggests increased
risk of dementia. J Neurol Neurosurg Psychiatry 2012; 83:1080.
151. Cantu RC. Chronic traumatic encephalopathy in the National Football League. Neurosurgery 2007; 61:223.
152. Guskiewicz KM, Marshall SW, Bailes J, et al. Association between recurrent concussion and late-life cognitive
impairment in retired professional football players. Neurosurgery 2005; 57:719.
153. Hart J Jr, Kraut MA, Womack KB, et al. Neuroimaging of cognitive dysfunction and depression in aging retired
National Football League players: a cross-sectional study. JAMA Neurol 2013; 70:326.
154. Lehman EJ, Hein MJ, Baron SL, Gersic CM. Neurodegenerative causes of death among retired National Football
League players. Neurology 2012; 79:1970.
155. Matser EJ, Kessels AG, Lezak MD, et al. Neuropsychological impairment in amateur soccer players. JAMA 1999;
282:971.
156. Matser JT, Kessels AG, Jordan BD, et al. Chronic traumatic brain injury in professional soccer players. Neurology
1998; 51:791.

17 of 24
 157. Martland, HS. Punch-drunk. JAMA 1928; 19:1103.
158. Jordan BD. Chronic traumatic brain injury associated with boxing. Semin Neurol 2000; 20:179.
159. Loosemore M, Knowles CH, Whyte GP. Amateur boxing and risk of chronic traumatic brain injury: systematic review
of observational studies. BMJ 2007; 335:809.
160. Ryan AJ. Intracranial injuries resulting from boxing. Clin Sports Med 1998; 17:155.
161. Plassman BL, Havlik RJ, Steffens DC, et al. Documented head injury in early adulthood and risk of Alzheimer's
disease and other dementias. Neurology 2000; 55:1158.
162. Goldstein LE, Fisher AM, Tagge CA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans and
a blast neurotrauma mouse model. Sci Transl Med 2012; 4:134ra60.
163. Miller G. Neuropathology. Blast injuries linked to neurodegeneration in veterans. Science 2012; 336:790.
164. McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013;
136:43.
165. Strain J, Didehbani N, Cullum CM, et al. Depressive symptoms and white matter dysfunction in retired NFL players
with concussion history. Neurology 2013; 81:25.
166. Ardila, A. Mendez, MF. Dementia pugilistica. In: MedLink Neurology, Gilman, S (Ed), MedLink Corporation, San
Diego 2010.
167. Schmidt ML, Zhukareva V, Newell KL, et al. Tau isoform profile and phosphorylation state in dementia pugilistica
recapitulate Alzheimer's disease. Acta Neuropathol 2001; 101:518.
168. Shively S, Scher AI, Perl DP, Diaz-Arrastia R. Dementia resulting from traumatic brain injury: what is the pathology?
Arch Neurol 2012; 69:1245.
169. Jordan BD, Relkin NR, Ravdin LD, et al. Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in
boxing. JAMA 1997; 278:136.
170. Kutner KC, Erlanger DM, Tsai J, et al. Lower cognitive performance of older football players possessing
apolipoprotein E epsilon4. Neurosurgery 2000; 47:651.
171. Han SD, Drake AI, Cessante LM, et al. Apolipoprotein E and traumatic brain injury in a military population: evidence
of a neuropsychological compensatory mechanism? J Neurol Neurosurg Psychiatry 2007; 78:1103.
172. Chamelian L, Reis M, Feinstein A. Six-month recovery from mild to moderate Traumatic Brain Injury: the role of
APOE-epsilon4 allele. Brain 2004; 127:2621.
173. Moretti L, Cristofori I, Weaver SM, et al. Cognitive decline in older adults with a history of traumatic brain injury.
Lancet Neurol 2012; 11:1103.
174. Johnson VE, Stewart W, Smith DH. Widespread and amyloid- pathology many years after a single traumatic brain
injury in humans. Brain Pathol 2012; 22:142.
175. Sivanandam TM, Thakur MK. Traumatic brain injury: a risk factor for Alzheimer's disease. Neurosci Biobehav Rev
2012; 36:1376.
176. Johnson VE, Stewart JE, Begbie FD, et al. Inflammation and white matter degeneration persist for years after a
single traumatic brain injury. Brain 2013; 136:28.
177. McKee AC, Gavett BE, Stern RA, et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic
encephalopathy. J Neuropathol Exp Neurol 2010; 69:918.
178. Al-Chalabi A, Leigh PN. Trouble on the pitch: are professional football players at increased risk of developing
amyotrophic lateral sclerosis? Brain 2005; 128:451.
179. Haley RW. Excess incidence of ALS in young Gulf War veterans. Neurology 2003; 61:750.
180. McMillan TM, Teasdale GM, Weir CJ, Stewart E. Death after head injury: the 13 year outcome of a case control
study. J Neurol Neurosurg Psychiatry 2011; 82:931.
181. Dams-O'Connor K, Gibbons LE, Bowen JD, et al. Risk for late-life re-injury, dementia and death among individuals
with traumatic brain injury: a population-based study. J Neurol Neurosurg Psychiatry 2013; 84:177.
182. Herring SA, Cantu RC, Guskiewicz KM, et al. Concussion (mild traumatic brain injury) and the team physician: a
consensus statement--2011 update. Med Sci Sports Exerc 2011; 43:2412.
183. Harmon KG, Drezner JA, Gammons M, et al. American Medical Society for Sports Medicine position statement:
concussion in sport. Br J Sports Med 2013; 47:15.
184. Guskiewicz KM, McCrea M, Marshall SW, et al. Cumulative effects associated with recurrent concussion in collegiate
football players: the NCAA Concussion Study. JAMA 2003; 290:2549.
185. Guidelines for the management of concussion in sports. Rev May 1991. Colorado Medical Society, Denver 1991.
186. Echemendia RJ, Iverson GL, McCrea M, et al. Advances in neuropsychological assessment of sport-related
concussion. Br J Sports Med 2013; 47:294.
18 of 24
 187. Halstead ME, Walter KD, Council on Sports Medicine and Fitness. American Academy of Pediatrics. Clinical report--
sport-related concussion in children and adolescents. Pediatrics 2010; 126:597.
188. Johnston KM, McCrory P, Mohtadi NG, Meeuwisse W. Evidence-Based review of sport-related concussion: clinical
science. Clin J Sport Med 2001; 11:150.
189. Sulheim S, Holme I, Ekeland A, Bahr R. Helmet use and risk of head injuries in alpine skiers and snowboarders.
JAMA 2006; 295:919.
190. Russell K, Christie J, Hagel BE. The effect of helmets on the risk of head and neck injuries among skiers and
snowboarders: a meta-analysis. CMAJ 2010; 182:333.
191. Hollis SJ, Stevenson MR, McIntosh AS, et al. Incidence, risk, and protective factors of mild traumatic brain injury in a
cohort of Australian nonprofessional male rugby players. Am J Sports Med 2009; 37:2328.
192. McIntosh AS, McCrory P. Impact energy attenuation performance of football headgear. Br J Sports Med 2000;
34:337.
193. Finch CF, McIntosh AS, McCrory P. What do under 15 year old schoolboy rugby union players think about protective
headgear? Br J Sports Med 2001; 35:89.
194. Hagel B, Meeuwisse W. Risk compensation: a "side effect" of sport injury prevention? Clin J Sport Med 2004;
14:193.
195. Schwarz A. As Injuries Rise, Scant Oversight of Helmet Safety. New York Times. 10/20/10. http://www.nytimes.com
/2010/10/21/sports/football/21helmets.html?pagewanted=1&_r=1&sq=sports%20and%20concussion&st=cse&
scp=27 (Accessed on October 23, 2010).

Topic 4828 Version 14.0

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 GRAPHICS

Glasgow coma scale

Score

Eye opening

Spontaneous 4

Response to verbal command 3

Response to pain 2

No eye opening 1

Best verbal response

Oriented 5

Confused 4

Inappropriate words 3

Incomprehensible sounds 2

No verbal response 1

Best motor response

Obeys commands 6

Localizing response to pain 5

Withdrawal response to pain 4

Flexion to pain 3

Extension to pain 2

No motor response 1

Total

The GCS is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of three
parameters: best eye response (E), best verbal response (V), and best motor response (M). The
components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS score of 9.
A score of 13 or higher correlates with mild brain injury; a score of 9 to 12 correlates with moderate
injury; and a score of 8 or less represents severe brain injury.

Graphic 81854 Version 2.0

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 Standardized assessment of concussion (SAC)

Delayed recall (Approximately 5

minutes after Immediate memory. 1
Orientation (1 point each) point each.)
Month Word 1

Date Word 2

Day of week Word 3

Year Word 4

Time (within 1 hr) Word 5

Orientation score: 5 Delayed recall score: 5

Immediate memory (1 point for each Summary of total scores:

correct, total over 3 trials) Orientation 5
Trial 1 Trial 2 Trial 3 Immediate memory 15

Word 1 Concentration 5

Word 2 Delayed recall 5

Word 3 Total score 30

Word 4 The following may be performed

Word 5 between the Immediate memory and
Immediate memory score: 15 Delayed recall portions of this
assessment when appropriate:
Concentration
Neurologic screening
Reverse digits (Go to next string length if
correct on first trial. Stop if incorrect on Recollection of the injury
both trials. 1 point each for each string Strength
length.)
Coordination
3-8-2 5-1-8
Exertional maneuvers
2-7-9-3 2-1-6-8
1 40-yard sprint
5-1-8-6-9 9-4-1-7-5
5 sit-ups
6-9-7-3-5-1 4-2-8-9-3-7
5 push-ups
Months of the year in reverse order (1 point
5 knee bends
for entire sequence correct)

Dec-Nov-Oct-Sep-Aug-Jul

Jun-May-Apr-Mar-Feb-Jan

Concentration score: 5

Reproduced with permission from: McCrea M, Kelly JP, Kluge J, et al. Standardized assessment of concussion in
football players. Neurology 1997; 48:586. Copyright 1997 Lippincott Williams & Wilkins.

Graphic 77142 Version 13.0

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 Standardized assessment of concussion addendum

Graded symptom checklist

Symptom None Mild Moderate Severe

Headache 0 1 2 3

Nausea 0 1 2 3

Vomiting 0 1 2 3

Dizziness 0 1 2 3

Poor balance 0 1 2 3

Blurred/double vision 0 1 2 3

Sensitivity to light 0 1 2 3

Sensitivity to noise 0 1 2 3

Ringing in the ears 0 1 2 3

Poor concentration 0 1 2 3

Memory problems 0 1 2 3

Not feeling "sharp" 0 1 2 3

Fatigue/sluggish 0 1 2 3

Sadness/depression 0 1 2 3

Irritability 0 1 2 3

Amnesia
Post-traumatic amnesia Yes No Length:

Retrograde amnesia Yes No Length:

Strength
Right arm Normal Abnormal

Right leg Normal Abnormal

Left arm Normal Abnormal

Left leg Normal Abnormal

Sensation Normal Abnormal

Coordination of limbs/gait Normal Abnormal

The unscored portion of the Standardized Assessment of Concussion (SAC) includes a graded symptom
checklist, a brief neurologic examination, and records the presence of post-traumatic and retrograde
amnesia.

Source: McCrea M. J Head Trauma Rehabil 1998 ; 13:27.

Graphic 67396 Version 3.0

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 Acute evaluation and disposition of patients with
mild TBI

Data from: Vos, PE. Eur J Neurol 2002; 9:207 and Borg, J. J Rehabil Med
2004; S43:61.

Graphic 50743 Version 3.0

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 Graduated return to play protocol

Rehabilitation Functional exercise at each

Objective of each stage
stage stage of rehabilitation

1. No activity Complete physical and cognitive rest Recovery

2. Light aerobic Walking, swimming or stationary cycling Increase HR

exercise keeping intensity <70 percent MPHR; no
resistance training

3. Sport-specific Skating drills in ice hockey, running drills Add movement

exercise in soccer; no head impact activities

4. Non-contact Progression to more complex training Exercise, coordination, and cognitive load
training drills drills, eg, passing drills in football and ice
hockey; may start progressive resistance
training

5. Full contact Following medical clearance, participate Restore confidence and assess functional
practice in normal training activities skills by coaching staff

6. Return to play Normal game play

Six-day return to play protocol. Each day the athlete makes a stepwise increase in functional activity, is
evaluated for symptoms, and is allowed to progress to the next stage each successive day if
asymptomatic.

Reproduced with permission from: 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 2009; 19:185. Copyright 2009 Lippincott Williams & Wilkins. Protocol unchanged in the 4th
International Conference (2012).

Graphic 61318 Version 9.0

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