Supplement

Contributions of neuroimaging, balance testing,

electrophysiology and blood markers to the
assessment of sport-related concussion
G A Davis,1 G L Iverson,2,3 K M Guskiewicz,4 A Ptito,5 K M Johnston6
1

Department of Neurosurgery,
Cabrini Hospital and Austin
Hospital, Melbourne, Victoria,
Australia; 2 University of British
Columbia, Vancouver, British
Columbia, Canada; 3 British
Columbia Mental Health &
Addiction Services, Vancouver,
British Columbia, Canada;
4
Department of Exercise and
Sport Science, University of
North Carolina at Chapel Hill,
Chapel Hill, North Carolina, USA;
5
Montreal Neurological Institute
& McGill University Health
Centre, Montreal, Quebec,
Canada; 6 Department of
Neurosurgery and Toronto
Rehabilitation Institute,
University of Toronto, Toronto,
Ontario, Canada
Correspondence to:
Associate Professor G A Davis,
Suite 53 Neurosurgery, Cabrini
Medical Centre, Malvern,
Victoria, 3144, Australia;
gadavis@netspace.net.au
Accepted 30 January 2009

ABSTRACT
Objective: To review the diagnostic tests and investigations used in the management of sports concussion, in
the adult and paediatric populations, to (a) monitor the
severity of symptoms and deficits, (b) track recovery and
(c) advance knowledge relating to the natural history and
neurobiology of the injury.
Design: Qualitative literature review of the neuroimaging,
balance testing, electrophysiology, blood marker and
concussion literature.
Intervention: PubMed and Medline databases were
reviewed for investigations used in the management of
adult and paediatric concussion, including structural
imaging (computerised tomography, magnetic resonance
imaging, diffusion tensor imaging), functional imaging
(single photon emission computerised tomography,
positron emission tomography, functional magnetic
resonance imaging), spectroscopy (magnetic resonance
spectroscopy, near infrared spectroscopy), balance testing (Balance Error Scoring System, Sensory Organization
Test, gait testing, virtual reality), electrophysiological tests
(electroencephalography, evoked potentials, event related
potentials, magnetoencephalography, heart rate variability), genetics (apolipoprotein E4, channelopathies) and
blood markers (S100, neuron-specific enolase, cleaved
Tau protein, glutamate).
Results: For the adult and paediatric populations, each
test has been classified as being: (1) clinically useful, (2) a
research tool only or (3) not useful in sports-related
concussion.
Conclusions: The current status of the diagnostic tests
and investigations is analysed, and potential directions for
future research are provided. Currently, all tests and
investigations, with the exception of clinical balance
testing, remain experimental. There is accumulating
research, however, that shows promise for the future
clinical application of functional magnetic resonance
imaging in sport concussion assessment and management.
Concussion in sports is common in the adult and
paediatric populations. A recent report indicates
that 207 830 patients per year with sports related
traumatic brain injuries are treated in US emergency departments.1 However, it has been estimated that only 819% of sports related head
injuries involve loss of consciousness, and the true
incidence of sports related head injuries resulting in
concussion is probably 1.63.8 million people per
year in the USA.1 This report estimates that the 5
18 years age group accounts for an estimated 65%
of emergency department visits for sports-related
traumatic brain injuries.

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The overall management of sport-related concussion includes preventive measures, diagnosis,

treatment, return to school/work/activity and
return to play decisions. The diagnosis of concussion is complicated because many concussions are
unrecognised or not reported, especially when
there is no loss of consciousness. In cases of
uncertainty, additional investigations may be
required to assist with the diagnosis. In recognised
and documented cases of concussion, sideline
assessment can involve the Sports Concussion
Assessment Tool (SCAT)2 or the Standardised
Assessment of Concussion (SAC).3
However, to monitor concussion severity and
recovery, and to assist with prognostication in the
concussed athlete, other tools and investigations
are required. The use of symptom monitoring and
neuropsychological testing, and the return-to-baseline paradigm, is now well established.2 4 However,
a multi-faceted approach using additional investigations can be helpful for a thorough management
of the injured athlete.
Despite the prevalence of sports concussion in
children, most of the research has been directed at
the management of young adults, particularly
collegiate and professional athletes. Children are
different from adults, not only in size, but also
biomechanically, pathophysiologically, neurobehaviourally and developmentally.5 6 It follows that a
diagnostic test developed and validated in adults
may or may not be applicable to the child. The
childs developing brain, and his/her physical,
academic, and emotional development, are factors
that might influence the neurobiology of the
injury, recovery time and management strategy.
Moreover, access to immediate assessment in
childrens sport is uncommon because the presence
of trained medical personnel on the sideline to
assess and manage concussion is rare. This situation is considerably different in collegiate and
professional sports.7
This review focuses on investigations carried out
in research and in specialised clinical management
programs. It does not address symptom scales,
sideline assessment or neuropsychological testing.
These assessment techniques are examined elsewhere within this supplement. Investigations
reviewed include structural and functional imaging, spectroscopy, balance testing, electrophysiological tests, genetics and blood markers.
The definition of concussion used in this review is
that of the concussion in sport group.2 8 It should be
noted that in many of the studies referred to in this
review, authors have used the terms concussion

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Supplement
and MTBI (mild traumatic brain injury) interchangeably. The
focus of this review is on concussions in athletes; for those other
head trauma studies in the literature, we have used the term
MTBI to differentiate injuries sustained by civilians. Thus, the
reader should note that in this review, when a referenced study
examined a civilian trauma sample rather than an athlete sample,
the term MTBI is used.

METHODS
The Medline and PubMed databases up to September 2008 were
searched using the term concussion with each of the
following terms: structural imaging (computerised tomography,
magnetic resonance imaging, diffusion tensor imaging), functional imaging (single photon emission computerised tomography, positron emission tomography, functional magnetic
resonance imaging (fMRI)), spectroscopy (magnetic resonance
spectroscopy, near infrared spectroscopy), balance testing
(Balance Error Scoring System (BESS), Sensory Organization
Test (SOT), gait testing, virtual reality), electrophysiological
tests (electroencephalography, evoked potentials, event related
potentials, magnetoencephalography, heart rate variability),
genetics (apolipoprotein E4, channelopathies) and, blood markers (S100, neuron-specific enolase, cleaved Tau protein,
glutamate). The review identified major and seminal publications that focused on diagnostic tests and investigations used in
concussion in sport. For those diagnostic tests lacking valid
published data in sport-related concussion, relevant publications
from the MTBI literature were analysed.
The studies for each diagnostic test and investigation were
reviewed and analysed to assess the validity of the diagnostic
test and investigation in each of the adult and paediatric
populations, as they relate to concussion in sport. For each
diagnostic test or investigation, a summary of the data was
synthesised for the adult and paediatric populations.

RESULTS
Structural imaging
Computed tomography
By definition, sport-related concussion is associated with
normal imaging studies, including computed tomography
(CT).2 However, in some individuals CT helps differentiate
sport-related concussion from a more serious MTBI. For
example, following a head injury, an individual may have a
normal neurological examination, yet may be harbouring an
intracranial haemorrhage or contusion. For those at risk of
intracranial haemorrhage, CT is the investigation of choice.
Published recommendations describe risk factors for intracranial
pathology in both adults9 10 and children.11 Although CT is
essential in the diagnosis of intracranial haemorrhage, it should
be noted that it has no utility in diagnosing or assessing
concussion per se. Given that a paediatric head CT exposes the
childs brain to 30 millisieverts of radiation,12 it should only be
used when clinically indicated.11

Magnetic resonance imaging

Conventional magnetic resonance imaging (MRI) includes T1weighted, T2-weighted, and fluid attenuated inversion recovery
images. These images provide exquisite detail of intracranial and
cerebral structure, and can identify occult lesions not visualised on
CT, such as small cerebral contusions.13 14 MRI has some
advantages over CT, such as multiplanar imaging, better lesion
detection, and it does not expose the patient to ionising radiation.
Concussion is defined as a functional disturbance rather than a
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structural injury, and as such, structural lesions identified on MRI

help to distinguish concussion from more serious MTBIs.15
Although there are a number of publications evaluating the
sensitivity of MRI in MTBI,13 14 1618 no study has addressed the
role of MRI in the management of paediatric or adult sport-related
concussion. This explains the absence of guidelines for using MRI
as a routine tool in the investigation of concussion. Furthermore,
many children, and some adults with claustrophobia may require
sedation or general anaesthesia while undergoing MRI and others
who have any metal parts in their body cannot undergo this type
of examination. In many countries, routine use of MRI for sportrelated concussion is not practical or feasible, given the number of
available machines, waiting lists and costs.

Diffusion tensor imaging

The movement of water molecules within white matter can be
measured by MRI, and diffusion tensor imaging (DTI) exploits
the fact that myelin sheaths and cell membranes of white
matter tracts restrict the movement of water molecules. Water
molecules diffuse in various directions in the brain, but often
travel along the length of axons which enables this technique to
create images of axons by analysing the direction of water
diffusion. DTI provides detailed structural images of white
matter tracts in the brain.19 20
DTI has been used primarily in research relating to brain
structure and function following civilian TBIs of all severities. It
has been used to assess white matter abnormalities following
MTBI,21 the length of white matter changes in patients21 with
MTBI, and the correlation between white matter damage and
simple reaction time.22 These studies revealed that MTBI can
affect the structural integrity of axons within the genu of the
corpus callosum, resulting in reduced functional anisotropy
(FA). Proposed causes of the decreased FA include misalignment
of fibres, oedema, fibre disruption or axonal degeneration. These
abnormalities correlate with increased reaction time at three
months post injury, which is consistent with studies revealing
correlations between white matter changes and the persistent
concussive symptoms in patients with a history of MTBI
compared to controls.23 Although DTI is being used more
commonly, its utility in adults has not yet reached the level of
diagnostic capabilities.
In a study of children aged 1018 years with mild and moderate
TBI, changes in FA were identified 612 months post injury.24
Wilde et al19 assessed adolescents aged 1417 years with MTBI and
normal CT and conventional MRI scans and found altered FA on
DTI within 6 days of injury, which they attributed to cytotoxic
oedema. Although DTI can be used to identify changes associated
with MTBI in some patients, no study has assessed its role in
concussion in children, and it therefore remains a research tool.
The technique is currently being utilised in prospective studies of
acute concussion in high school athletes (University of
Pittsburgh), collegiate athletes (University of North CarolinaChapel Hill, University of Pittsburgh and McGill University) and
long-term effects of concussion in retired professional football
players (University of North Carolina-Chapel Hill and National
Football League MTBI Committee). These studies will attempt to
identify the clinical correlates of DTI.

Functional imaging
Single photon emission computerised tomography
Single photon emission computerised tomography (SPECT)
involves intravenous injection of a radioisotope (eg, technetium99m) followed by acquisition of brain images from a scintillation
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gamma camera. Essentially, SPECT measures regional cerebral
blood flow. Some preliminary work in adults with MTBI
identified SPECT abnormalities in the medial temporal lobe,25
and a small study on children (ages 218) with MTBI suggested
that medial temporal hypoperfusion on SPECT was associated
with persistent post-concussion syndrome.26 This latter study
with children had many scientific limitations, including the lack
of clinical data, small numbers, and no neuropsychological
assessment. A methodological problem with SPECT is that
analyses are typically done by comparing a region of interest in
the brain to another part of the same brain that is believed to be
normal in function (such as in stroke or brain tumour research).
The problem, of course, with traumatic brain injury is that the
brain can be affected diffusely. When considering the use of
SPECT in children, one must be cognisant of the fact that it does
expose the child to a radioisotope, and as such, this limits its use as
a widespread routine diagnostic tool. The therapeutics and
technology assessment subcommittee of the American Academy
of Neurology has cautioned against the routine use of SPECT for
the evaluation of patients with mild traumatic brain injury or
post-concussion syndrome.27

Positron emission tomography

Positron emission tomography (PET) can be used to measure
aspects of cerebral metabolism, including blood flow and
metabolic rate for oxygen. PET relies on radionuclides (eg, 2(F-18) fluoro-2-deoxyglucose (FDG)), produced from a cyclotron, that have very short half lives. Following intravenous
injection of FDG, the radionuclide crosses the blood-brain
barrier and is taken up by brain cells. The patient is then imaged
within the PET scanner and the images display regions of brain
metabolism. Preliminary data in adults with MTBI and
persistent symptoms up to seven years post injury suggested
an area of medial temporal hypometabolism.25 Chen and
colleagues28 used PET to study five adults with MTBI and
persistent symptoms at rest and during a spatial working
memory task. They found normal regional cerebral FDG uptake
at rest; however, minor differences emerged during the visualspatial working memory task. PET does require the use of a
radio labelled tracer, limiting its use in children with concussion.
Moreover, PET is very expensive and time consuming; it is still a
research tool in the field of MTBI.

Functional magnetic resonance imaging

Dynamic techniques, such as fMRI, can offer insights into the
pathophysiological and functional sequelae of concussive
injuries.29 fMRI studies are non-invasive and do not require
the use of a radioactive tracer. fMRI detects the consequence of
neuronal activation in cortical matter by observing regional
changes in either T1 from increased blood perfusion or T2 from
reduced paramagnetic deoxyhaemoglobin levels. The most
common approach is based on blood oxygenation changes,
and the signal contrast generated has been termed BOLD, for
blood oxygenation-level dependent.30
Abnormalities on fMRI have been associated with the
presence of post-concussion symptoms (PCS),31 32 and the
severity (mild, moderate, severe) of these symptoms.33 Chen et
al31 compared brain activations of 16 (15 symptomatic, one
asymptomatic) concussed athletes with a group of eight normal
controls using working memory tasks. All the athletes but one
had subjective complaints of PCS at the time of the functional
imaging study. The one symptom-free athlete showed an
activation pattern similar to that of the control group, and all
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the symptomatic athletes displayed a different activation

pattern, regardless of whether they experienced loss of
consciousness at the time of the injury. Jantzen et al34 performed
baseline BOLD activity in eight college football players; four
concussed players repeated the fMRI within one week of injury.
They found that concussed players had increased BOLD activity
during a finger-sequencing task.
Recovery and compensatory patterns may also be seen on
fMRI when serial follow-up is available.35 Some researchers have
correlated fMRI abnormalities with cognitive test results. Lovell
et al32 presented fMRI results for 28 concussed athletes. They
performed a measure of working memory (N-back task) using
fMRI soon after concussion, and then repeated the fMRI
following clinical and neuropsychological recovery. Those
athletes with hyperactivation on fMRI at the time of their first
scan had a more prolonged clinical recovery than those who did
not have hyperactivation.
Normative data is being collected and can now be used to
determine whether the BOLD signal change of a concussed
individual deviates from the normal pattern, based on the
methodology of Chen and colleagues.31 This might be useful for
evaluating clinical outcome, especially in cases where symptoms
persist and morphological imaging results are normal. In
addition to somatic symptoms (eg, headaches and fatigue) and
cognitive deficits (eg, concentration, memory and executive
functioning), there can be psychiatric complications, such as
anxiety, irritability and depression. Most studies on sport
concussion have focused on the somatic and cognitive aspects,
while the psychiatric dimension remains largely unexplored.
Chen et al36 compared fMRI between 24 athletes with
concussion who complained of depression, 16 athletes with
concussion who did not complain of depression and 16 noninjured control athletes. They found that in athletes with
symptoms of depression fMRI results are similar to functional
neuroimaging findings in major depression, suggesting that
depression following sport concussion may share similar
underlying neural mechanisms as major depressive disorder.
Although fMRI has yielded important information relating to
neurobiology and recovery in adults with concussion, no study has
specifically addressed its use in children. The utility of fMRI
depends not only on the technological capabilities of the MRI
machine, but also on the paradigms utilised in performing fMRI
such as finger sequencing techniques, N-back memory assessment,
and other verbal and visual memory tasks. The interpretation of
these paradigms in children at different stages of development, and
the resultant fMRI correlates, is yet to be established. Furthermore,
the paradigms used in fMRI assess focal regions of the brain, and
are taken as surrogate measures of global function. To what extent
this is true in the developing brain is unknown.
fMRI is relatively expensive and inaccessible for most clinical
needs. The BOLD signal is an indirect measure of neural
activity, and is therefore susceptible to influence by non-neural
changes in the body. Other variables that are difficult to control
for such as medications, fatigue, substance use, and pain may
play a role and should be taken into consideration when
interpreting results.37 fMRI remains at this time a research tool,
although its future as a useful diagnostic technique is promising.

Spectroscopy
Magnetic resonance spectroscopy
Whereas MRI detects signal from water and lipids, magnetic
resonance spectroscopy (MRS) detects signals from individual
chemicals in tissue. There are two commonly used types of
MRS: proton and phosphorus. In proton MRS the four major
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Supplement
Figure 1 Review of serial fMRI studies.
(a) Group average serial activation maps
from 4 healthy normal athletes with no
post-concussive symptoms (PCS). Note:
Similar areas of activation suggest
reasonable stability of fMRI findings from
Baseline Study 1 to Baseline Study 2; (b)
Group average activation maps (n = 8) for
working memory tasks, superimposed on
the groups average MRI, at baseline (PCS
score = 4) and after concussion
(,72 hrs; PCS score = 27). Note
reduced activations correlate with
presence of symptoms immediately after
concussion; (c) Group average serial
activation maps from another group of
four concussed athletes whose
symptoms improved from Study 1 to
Study 2 compared to five concussed
athletes whose symptoms did not
resolve. Note: emerging task-related brain
activities in the frontal region are
observed only in those athletes whose
symptoms improved; a lack of activity in
the frontal region remains in those with
persistent symptoms.
compounds present are N-acetyl aspartate (NAA), creatine,
choline and myo-inositol. NAA, creatine and choline are found
in neuronal and glial cells. Myo-inositols are found predominantly in glial cells. Creatine is involved in cellular energy
metabolism, myo-inositol is an organic osmolyte, choline is a
constituent in the cytosol and cellular membranes and NAAs
function is unknown.38 Lactate, which is used as a marker for
anaerobic metabolism, is present in very low levels in control
individuals but may be elevated in diseased states. Phosphorus
MRS identifies peaks of ATP, phosphocreatine and inorganic
phosphate, all of which are involved in the high-energy
metabolism of the cells.
Changes in NAA, choline and creatine have been identified on
MRS in individuals following traumatic brain injury.39 40
However there is no study examining the use of MRS in
concussion. MRS remains a research tool.

Near infrared spectroscopy

Near infrared spectroscopy (NIRS) can be used to detect changes
in blood haemoglobin concentrations associated with brain
activity. NIRS can be used as a non-invasive technique for
evaluating cerebral blood volume and oxygenation, and it has
been used to monitor cerebral haemodynamics during exercise
following a sport-related concussion.41 When a particular cerebral
area is activated, the local increase in oxygenated blood is greater
than the amount of oxygen that can be extracted by the brain
tissue, such that the proportion of oxygenated and deoxygenated
blood changes in the localised region of the brain.42 Blood volume
changes using NIRS can be used to provide an estimate of blood
flow.43 NIRS remains a research tool in adults and no data are
available pertaining to its use in children.

Balance testing
Traumatic injuries to the head and brain can result in
temporary or permanent deficits in static or dynamic balance.4450 In sports medicine, balance testing has been used to
document the presence of concussive brain injury and to track
recovery.5053
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Balance Error Scoring System

A commonly used measure of static balance and postural
stability is BESS.50 51 53 54 The test is rapid, easy-to-administer,
and inexpensive. A combination of three stances (narrow double
leg stance; single leg stance; and tandem stance) and footing
surfaces (firm surface/floor or medium density foam) are used
for the test (fig 2). Each stance is held, with hands on hips and
eyes closed, for 20 seconds. Error points are given for specific
behaviours, including opening eyes, lifting hands off hips, or
stepping, stumbling or falling.
McCrea and colleagues50 reported that BESS scores in
concussed college football players changed from baseline on
average by 5.7 points, when measured immediately following
the game or practice in which the injury occurred. Notably,
however, at 1 day post injury, their average BESS score was only
2.7 points greater than baseline. For most athletes, BESS
performance returned to preseason baseline levels (average 12
errors) by 37 days post injury. These modest changes in BESS
performance and rapid recovery of static balance have been
reported in other studies with athletes.5153 In a large study of
American collegiate football players, impairment on the BESS
was seen in 36% of injured subjects immediately following
concussion, compared to 5% of the control group. Of the injured
subjects, 24% remained impaired on the BESS at 2 days post
injury, compared to 9% by day 7 post injury. Sensitivity values
for the BESS were highest at the time of injury (sensitivity
= 0.34). Specificity values for this instrument ranged from 0.91
to 0.96 across post-injury days 17.55
Significant correlations between the BESS and force platform
sway measures with normal subjects have been established for
five static balance tests (single leg stance-firm surface, tandem
stance-firm surface, double leg stance-foam surface, single leg
surface-foam surface, and tandem stance-foam surface), with
inter-rater reliability coefficients ranging from 0.78 to 0.96.56
Researchers have reported that BESS performance can be
influenced by a number of factors, including the type of sport
played,57 a history of ankle injuries and ankle instability58 and
exertion and fatigue.59 60 Healthy athletes typically demonstrate
a subtle learning (ie, practice) effect on the BESS when it is
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Figure 2 Balance Error Scoring System
(BESS) performed on firm surface (A-C)
and foam surface (D-F).

administered over brief retest intervals.61 62 This should be

considered when interpreting post-injury results during serial
testing.
Several studies have identified BESS deficits ranging from 3
5 days post concussion when compared to baseline and control
subjects.50 51 53 The BESS is sensitive to the effects of concussion
with and without the use of other brief screening instruments
such as a graded symptom checklist and the SAC.55 However,
when used in combination with a graded symptom checklist
and the SAC, the BESS is more sensitive and specific for
accurately classifying injured and non-injured athletes during
the acute post-injury phase.50 55 As of 2004, approximately 16%
of certified athletic trainers in the USA reported using the BESS
to evaluate a concussion.63 Other research has suggested that the
test has clinical utility across many age groups.63 64

Sensory Organization Test

The SOT (NeuroCom International, Inc., Clackamas, OR, USA)
is a technical force plate system used to assess balance following
concussion.51 65 66 The SOT systematically disrupts the sensory
selection process by altering the orientation information
available to the somatosensory and/or visual inputs while at
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the same time measuring the subjects ability to maintain a

quiet stance. Sway referencing is used throughout the test
because the movement of the platform beneath the patients
feet and the environmental surround move in response to the
athletes anterior/posterior sway. The SOT uses six different
conditions; each is performed three times to assess balance
(fig 3).
The SOT appears to be a useful clinical tool for detecting
sensory interaction and balance deficits following concussion.51 66 67 Similar to the studies involving clinical balance tests,
those using the SOT have identified deficits averaging about
3 days post injury.51 56 These studies indicate that the centres of
the brain responsible for coordinating the sensory modalities
(thalamus and its interconnective pathways to the cerebral
cortex) may be disrupted for periods lasting up to 3 days postinjury. There is a subtle practice effect with both the BESS and
SOT, so the absence of this improvement in concussed athletes
with repeated testing should be carefully monitored. These
studies also suggest that the sensory system most often affected
following concussion is the vestibular system and that the
system most relied upon by healthy individuals is the
somatosensory system.51 More recently, Broglio et al68 illustrated
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Electrophysiology
Electroencephalography, evoked potentials and event-related
potentials

Figure 3 Six testing conditions (16) for the Sensory Organization Test
used with NeuroComs Smart Balance Master.

the usefulness of using the SOT as the balance portion of a dual

task with attention divided between the balance task of the
SOT and another cognitive task. The use of the SOT is mainly
confined to a clinic or a laboratory setting because of its
technology needs and size; however, it can be useful in difficult
cases following a concussive injury and utilised as a more
technical and refined measure of balance performance.
One recent study suggested that the test-retest reliability of
the SOT in normal controls is low to moderate,65 raising an issue
with regard to serial testing. Furthermore, the SOT is not a
functional balance task in that it uses a double leg stance
throughout. Despite the benefit of altering sensory feedback and
detecting sensory interaction deficits, it may not be as sensitive
as a more difficult task performed on foam with a single leg.

Gait testing
Parker et al69 examined 29 college athletes (mean age 21 years)
who had sustained a concussion and performed neuropsychological testing and gait stability testing on days 2, 5, 14 and 28
post injury. Gait was tested as a single-task, and then while
completing a simple mental task (dual-task). A persistent
significant difference was noted in the dual-task gait assessment
at day 28, although not in the single-task or neuropsychological
assessment. Additional research in this area with children and
adults is warranted.

Electroencephalography (EEG) records the electrical properties

of neurons by placing electrodes on the scalp. Although EEG has
revealed abnormalities post-concussion, its clinical significance
is uncertain. Thompson et al71 evaluated 12 male athletes (age
1825 years) who had sustained MTBI (70131 days pretesting) with EEG in four ways: (1) eyes open-seated; (2) eyes
closed-seated; (3) eyes open-standing; (4) eyes closed-standing.
They found under each condition an overall decrease of EEG
amplitude, especially during standing postures, and postural
instability was greatest when eyes were closed. The significance
of these changes in adult and paediatric sport-related concussion
is yet to be established.
Evoked potentials (EP) and event-related potentials (ERP)
represent the averaged EEG signal in response to a given
stimulus, with EP thought to represent processing in the
primary sensory pathways, and ERP being associated with
cognitive processes.72 The best known among ERP studies is the
P300 component.7376 Although ERP has good temporal resolution, this technique has poor spatial resolution, which makes it
more difficult to localise the brain region responsible for the
abnormal activity. Recent studies have reported good sensitivity
of ERP for measuring the impact of concussions on cognitive
functions in athletes.7781 In athletes, the presence of symptoms
and the number of concussions previously sustained appear to
predict the P300 characteristics in oddball paradigms.7881 The
use of ERP in the paediatric population has not been established.

Magnetoencephalography
Due to the current flow within the dendrites, neuronal
dendrites oriented parallel to the skull surface produce a
magnetic field. This magnetic field can be measured outside
the head using supercooled sensors connected to superconducting quantum interference devices. This is the basic principle of
magnetoencephalography (MEG). In a retrospective review of
30 adults with persistent (.1 year) symptoms following nonsport-related MTBI (predominantly motor vehicle accidents),
Lewine et al18 used MEG, MRI and SPECT imaging, and reported
abnormalities in 73% of the patients. They found that MEG
findings did not correlate well with psychiatric or somatic
symptoms, but there was an association between MEG and
cognitive problems.18 However, the lack of baseline neuropsychological data limits the interpretation of these results. There
is no data available for use of MEG in paediatric concussion.
The use of MEG is limited because it is expensive and requires
installation in magnetic-shielded rooms. Presently there are
fewer than 25 whole-head MEG systems in the USA. MEG
remains a research tool.

Heart rate variability

Virtual reality
Slobounov et al70 tested balance in eight concussed athletes (age
1825 years) at days 3, 10 and 30 post injury. Subjects were
exposed to a virtual reality image of the room moving. They
found that standard balance testing recovered by day 10, but
responses to visual field motion remained abnormal at day 30.
In all eight athletes, symptoms and neuropsychological testing
had returned to baseline. The clinical significance of altered
response to virtual reality, rather than to static balance, is yet to
be established.
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Numerous factors play a role in the minute-to-minute changes

in cardiac function, including the balance between the
sympathetic and parasympathetic nervous systems. During
the day, there is greater sympathetic influence on heart rate,
while at night there is increased parasympathetic influence.
Greater sympathetic activation has at least two effects on
cardiac functioning: increased heart rate and decreased heart
rate variability. Increased parasympathetic activity that occurs
during the night has the opposite effect: decreased heart rate
and increased heart rate variability.82
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Researchers have examined heart rate variability in children
and adults who have sustained severe or catastrophic brain
injuries from trauma or other causes.8387 Power spectral analysis
of heart rate variability diminishes in proportion to the degree of
neurological injury.88 There appears to be a physiological
uncoupling of the autonomic and cardiovascular systems
following acute brain injury.88 89
There have been two published studies of cardiac functioning
following concussion in athletes. Gall, Parkhouse and
Goodman90 examined heart rate response in 14 concussed
athletes after they were asymptomatic at rest in comparison
to 14 healthy controls. Athletes who had missed playing time
had elevated heart rates in response to an exercise protocol on a
cycle ergometer relative to control subjects. No significant
differences in subjectively reported post-concussion symptoms
were noted, however. The differential heart rate response
occurred in the absence of obvious changes in post-concussion
symptoms, and may reflect a subtle and lingering neuroautonomic cardiovascular effect. These same researchers analysed
heart rate variability in these subjects.91 There were no
differences in heart rate variability associated with concussion
when the athletes were at rest. However, heart rate variability
differences emerged following exercise testing. They concluded
that the pathophysiology of concussion might not be reflected
in neuroautonomic cardiovascular dysfunction at rest, but
might be elicited through exertion protocols.
Heart rate variability analyses, in concussed athletes, merits
further study. The clinical use of measures of heart rate
variability is yet to be established in adult and paediatric
concussion.

Genetics
Aolipoprotein E gene
Studies in severe traumatic brain injury have shown that
possession of the e4 allele of the apolipoprotein E gene (ApoE4)
is associated with worse outcome. Subsequently, the question
has been raised as to whether ApoE4 predisposes to worse
outcome in concussion. Kutner et al92 examined 53 active
American professional football players and performed cognitive
testing and ApoE genotyping on each player. They found that
those older players who possessed ApoE4 exhibited lower than
expected cognitive performance. However, those younger
players with ApoE4 did not have a significant reduction in
cognitive performance.
Kristman et al93 examined the rate of sustaining a concussion
in 318 university athletes and found no significant association
between carrying ApoE4 and the rate of injury. Smith et al94
examined fatal cases of traumatic brain injury and found a
greater incidence of moderate/severe contusion and ischaemic
brain injury in those with ApoE4. They suggest that ApoE may
play a role in blood vessel wall integrity and coagulation of
blood. This may explain the association of ApoE4 with poor
outcome in severe traumatic brain injury, but its role in
concussion is yet to be determined.
Terrell et al95 performed a retrospective review of 196 college
athletes who completed a concussion history questionnaire, and
found an association between the ApoE promoter TT genotype
and a history of concussion.95 However, the group with a selfreported history of concussion reported participating in sport
for more years than those without a history of concussion.
If ApoE4 does predispose an athlete to a more severe concussion
for a given injury, or, as Kutner et al92 suggest, long-term cognitive
decline, then ethicists may assert that a child who possesses
ApoE4 should be precluded from participating in contact sports.
i42

At this time, no study has examined ApoE4 status in children and

prospectively observed them during and following their sporting
careers.

Channelopathies
Channelopathies are disorders caused by inherited mutations of
ion channels.96 A number of channelopathies have been
described affecting brain and muscle. For example, the three
types of familial hemiplegic migraine are associated with gene
mutations on chromosomes 19p, 1q and 2q respectively.96 The
possibility that a channelopathy could predispose an individual
to more severe forms of concussion or post-concussive migraine
is open to conjecture, and could be the subject of future
research.

Blood markers
S100 proteins, neuron-specific enolase and cleaved Tau protein
There is considerable interest in blood-based biomarkers of
traumatic brain injury in the civilian trauma literature.97104
Brain serum S-100 protein is a mixture of S-100A1 and S-100B
proteins; the S-100B immunoreactivity most commonly cited in
the literature refers to the summed concentrations of the S-100B
monomers in S-100A1B and S-100BB.105 This protein is found in
astroglial and Schwann cells. It is believed to be a fairly sensitive
blood marker for brain damage.
Researchers have reported that S100B is elevated following
traumatic brain injury of all severities in civilian trauma
patients.98 101 104 106 107 There is an association between elevated
S100B and structural abnormalities detected on CT scan.98 103
105 107109
In one study, elevated S100B was associated with lower
return to work rates at one-week post MTBI.110 Other
researchers, however, have reported weak or no clear relation
between S100B levels and neuropsychological outcome.111113
S100B testing is not widely available in emergency departments. As a blood-based biomarker, it is not very practical to use
in sport concussion clinical management or research because it
needs to be collected as soon as possible after the injury, ideally
within 4 hours. Moreover, there is evidence that S100B (in
lower concentrations) can be detected in the serum of athletes
engaged in sporting activities114116 and in civilians with soft
tissue or orthopaedic injuries.105 117
A detailed review by Begaz et al118 summarised studies
examining S100 proteins, neuron-specific enolase and cleaved
Tau protein, and concluded that no biomarker had consistently
demonstrated the ability to predict post-concussion syndrome
after MTBI. Therefore, these blood markers remain as research
tools in the management of adult and paediatric concussion.

Glutamate
Research into excitatory neurotransmitters (eg, glutamate) is
proceeding. In a study of autoantibodies to glutamate receptors
in children aged 716 years with chronic post-traumatic
headache, hyper-stimulation of glutamate receptors was
reported.119 However, some of these children had sustained
cerebral contusions and the application of this testing to
paediatric sports concussion has not been established.

Conclusions & directions for future research

Significant developments in the past decade have advanced
research into sport-related concussion. This review has examined the use of some diagnostic tests and investigations that can
be utilised in a return-to-baseline paradigm similar to neuropsychological assessment. Advanced applications have developed
Br J Sports Med 2009;43(Suppl I):i36i45. doi:10.1136/bjsm.2009.058123

Supplement
What is already known on this topic
The current recommendations for assessment of concussion are
predominantly clinical, requiring resolution of all symptoms and
signs, and the use of return-to-baseline neuropsychological
assessment. While anecdotal relationships have been reported
between symptomatology and diagnostic tests, many of these
relationships are unsubstantiated in the literature. Therefore, the
application of diagnostic tests and investigations to the clinical
domain is uncertain.

What this study adds

The use of clinical balance testing has developed increasing
acceptance in the management of concussion. fMRI and DTI are
presently research tools, but demonstrate great potential as
clinical tools. Genetic testing and blood markers are yet to
demonstrate clinical utility. Electrophysiological research may
provide significant insights into the neurobiology of sports-related
concussion. The utility of some tools may be less sensitive for
diagnostic purposes in the paediatric population compared to the
adult population.

with fMRI and balance testing for assessing concussed athletes

with a multi-faceted approach. At this time, all tests and
investigations, with the exception of clinical balance testing,
remain experimental. There is accumulating research, however,
that shows promise for the future clinical application of fMRI in
sport concussion assessment and management.
There are several directions for research with fMRI.
Important research questions include: (1) Which symptoms
are most important and are there particular ones that correlate
with fMRI activation patterns? (2) Is there evidence for residual
injury after symptoms have resolved, the athlete has returned to
play, and he/she is presumed recovered? (3) What is fMRIs
contribution in the paediatric population and will those findings
be similar to those obtained in adults? (4) Are there important
sex differences?
Balance testing has been examined using different paradigms,
such as BESS, SOT, gait testing and virtual reality. Although the
BESS is not a truly functional task, it can be administered
rapidly, inexpensively and it has evidence to support its validity
and clinical use, especially during the acute post-injury period
(15 days). The BESS is a standardised and objective measure of
postural stability and coordination following injury, and can be
used as an additional outcome measure when considering return
to play. Whether the addition of more complicated balance
testing involving dual tasks or virtual reality will improve
clinical decision-making is yet to be established. Further research
should focus on interpretation of balance testing following
concussion within the setting of athlete fatigue, musculoskeletal injury, medication use, different sports, age groups and
gender.
Although not appropriate for use in the general clinic,
electrophysiological research may provide significant mechanistic understanding in sport-related concussion, in particular the
use of MEG combined with other modalities, such as fMRI. At a
cellular level, further research into genetics or ion-channels may
provide concussion risk-stratification of athletes.
The developing brain in the paediatric population necessitates
careful analysis of each test as it applies to the concussed child,
Br J Sports Med 2009;43(Suppl I):i36i45. doi:10.1136/bjsm.2009.058123

with a clear understanding that the child athlete faces the

challenge of return to school and learning, in addition to return
to sport. Sports-related injury in the child may disrupt already
established cerebral functions, and could possibly affect brain
development. Research into paediatric sport-related concussion
must examine the impact of brain development on diagnostic
test interpretation.
This review has described many significant research achievements in the development of diagnostic tests and investigations
in sports concussion. A tremendous amount of research and
technological advancement will be necessary before most of
these investigations have practical clinical value in the day-today management of athletes with concussions. Researchers
should continue to strive to identify tests that are reliable in the
early diagnosis of concussion, that predict concussion severity
and duration, that monitor progress and recovery, and provide
results that enhance return-to-play decision-making. Such tests
must be widely available in the general community, affordable,
and be appropriate for use in both adult and paediatric sports
concussion.
Competing interests: None.

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i45

Contributions of neuroimaging, balance

testing, electrophysiology and blood markers
to the assessment of sport-related
concussion
G A Davis, G L Iverson, K M Guskiewicz, A Ptito and K M Johnston
Br J Sports Med 2009 43: i36-i45

doi: 10.1136/bjsm.2009.058123
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http://bjsm.bmj.com/content/43/Suppl_1/i36

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