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Cerebrovascular reactivity assessed by transcranial
Doppler ultrasound in sport-related concussion:
a systematic review
Andrew J Gardner,
1
Can Ozan Tan,
2,3
Philip N Ainslie,
4,5
Paul van Donkelaar,
6
Peter Stanwell,
7
Christopher R Levi,
8
Grant L Iverson
9
For numbered affiliations see
end of article.
Correspondence to
Dr Andrew J Gardner, Centre
for Translational Neuroscience
and Mental Health, University
of Newcastle, Level 5, McAuley
Building, Calvary Mater
Hospital, Waratah, NSW 2298,
Australia;
andrew.gardner@neurogard.
com.au
Accepted 9 November 2014
To cite: Gardner AJ,
Tan CO, Ainslie PN, et al.Br
J Sports Med Published
Online First: [please include
Day Month Year]
doi:10.1136/bjsports-2014-
093901
ABSTRACT
Background Traumatic brain injury influences
regulation of cerebral blood flow in animal models and
in human studies. We reviewed the use of transcranial
Doppler ultrasound (US) to monitor cerebrovascular
reactivity following sport-related concussion.
Review method A narrative and systematic review of
articles published in the English language, from
December 1982 to October 2013.
Data sources Articles were retrieved via numerous
databases using relevant key terms. Observational,
cohort, correlational, cross-sectional and longitudinal
studies were included.
Results Three publications met the criteria for
inclusion; these provided data from 42 athletes and 33
controls. All three studies reported reductions in
cerebrovascular reactivity via transcranial Doppler US.
Conclusions These initial results support the use of
cerebrovascular reactivity as a research tool for
identifying altered neurophysiology and monitoring
recovery in adult athletes. Larger cross-sectional,
prospective and longitudinal studies are required to
understand the sensitivity and prognostic value of
cerebrovascular reactivity in sport-related concussion.
INTRODUCTION
Most major guidelines for management of
sport-related concussion call for physical rest
acutely after injury, with graded return to exertion
and exercise after concussion symptoms resolve,
although the evidence behind this recommendation
is limited.
1–3
Most athletes appear to recover symp-
tomatically from a concussion between 2 and
28 days (with the large majority of cases recovering
in 5–10 days) following injury,
4–6
although a small
percentage experience persisting symptoms.
78
Even if overt symptoms are gone at rest and with
light exertion, strenuous effort (such as return to
sports) may induce symptoms.
9
Clinically, this is
often observed as exertion-induced headache, con-
fusion or dizziness and it presents a major obstacle
to full return to sport.
At present, the mechanisms that may underlie
the link between sports-induced concussion, strenu-
ous activity and postconcussion symptoms are not
well understood. Impaired responsiveness of cere-
brovasculature to changes in arterial carbon dioxide
(CO
2
; ie, impairment in cerebrovascular reactivity)
may play a role. The pathophysiology of impaired
cerebrovascular reactivity in the setting of concus-
sion is not understood. We reviewed data on the
link between sports-related concussion,
cerebrovascular reactivity and postconcussion
symptoms (initial or exertion-induced).
Cerebral vasoreactivity and traumatic
brain injury
The ability of the cerebral vasculature to maintain
steady supply of oxygenated blood in the face of
changing arterial CO
2
, that is, cerebral vasoreactiv-
ity, is critical to neurophysiological health. Cerebral
blood flow is strongly influenced by alterations in
arterial CO
2
concentrations. Cerebral vessels dilate
in response to increased arterial CO
2
(ie, in
response to hypercapnia) and constrict in response
to reduced arterial CO
2
(ie, in response to hypo-
capnia). These responses are rapid, occurring with
approximately 6 s delay,
10
and are vital to regulate
and maintain central pH.
There is some evidence linking traumatic brain
injury (TBI) impaired cerebral vasoreactivity and
outcomes. For example, impaired cerebral vasoreac-
tivity in the initial days following severe injury pre-
dicts poor outcomes.
11 12
Moreover, a disruption
in cerebrovascular reactivity occurs in the days
immediately after a mild cortical impact injury in
animals,
13
and shortly after sports-related concus-
sion.
14
Anecdotal evidence suggests that symptoms
similar to those associated with concussion (specif-
ically, headache) can arise, at least in part, as a
result of derangement in cerebral vasoreactivity. For
example, individuals with migraine demonstrate
excessive increases and decreases in cerebral blood
flow in response to hypercapnia and to hypocapnia
that might be associated with the development and/
or persistence of headaches.
15
A long-lasting
impairment in cerebral vasoreactivity could relate
to exertion-induced postconcussive symptoms.
Mild to moderate exertion is associated with a
small increase in arterial CO
2
(ie, hypercapnia) that
increases cerebral blood flow.
16
However, with
increasing intensity of exercise, ventilation increases
exponentially with work rate, resulting in a reduc-
tion in arterial CO
2
(ie, hypocapnia). Thus, intense
exercise is accompanied by decreases in cerebral
blood flow; this ultimately interferes with adequate
oxygenation of the brain,
17
especially if cerebral
vasoreactivity is impaired (figure 1).
Physiology and pathophysiology of
cerebrovascular reactivity: implications for
sports-related concussion
The specifics of the physiology that underlies cere-
bral vasoreactivity are largely unknown, but avail-
able data suggest that the endothelial nitric oxide
Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901 1
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(NO) system has a necessary role in the normal cerebrovascular
response to carbon dioxide changes, and animal and in vitro
studies of brain injury have shown that NO is among the
biochemical mediators in the post-traumatic phase.
18
NO is
involved in the pathogenesis of neuronal damage after experi-
mental brain trauma. NO synthase is induced by experimental
contusions in animals.
19–21
However, the exact role of elevated
NO after injury remains controversial. Inhibition of NO syn-
thase has been shown to increase mortality
22
and also reduce
neurological deficits
23
after experimental contusion in rats. It is
possible that different isoforms of NO synthase may have differ-
ent roles. For example, it appears that NO produced by endo-
thelial NO synthase may be protective, whereas NO produced
by neuronal NO synthase causes cellular damage in traumatised
brain tissue.
21
Consistent with a neuroprotective role, there is
enhanced expression of endothelial NO synthase in the micro-
vasculature surrounding the area of impact after moderate trau-
matic injury in rats.
20
Regardless of its possible neuroprotective
role, overproduction of NO in the cerebrovasculature in patho-
logical states (including TBI) may lead to excessive vasodilation
and abnormal vascular permeability.
24
Therefore, it is possible that overproduction of endothelial
NO after sports-induced concussion may lead to increased
blood flow and impaired cerebral vasoreactivity. As mentioned
above, excessive increases and decreases in cerebral blood flow
in response to hypercapnia and to hypocapnia might be asso-
ciated with the development and/or persistence of headaches.
15
Figure 1 Exercise intensity effects for cerebrovascular reactivity (CVR).
Figure 2 PRISM flow diagram. CVR, cerebrovascular reactivity.
2 Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901
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Thus, and given that exertion and physical activity is associated
with alterations in arterial CO
2
, it is conceivable that altered
cerebral vasoreactivity due to dysregulation of the endothelial
NO system might partially underlie initial and exertion-induced
symptoms after sports-related concussion. If true, this link
opens up new venues for treatment and recovery. To further
explore this link, we examined studies that have assessed cere-
bral vasoreactivity following sport-related concussion by system-
atically reviewing available observational (ie, no intervention
was applied), cohort, correlational, cross-sectional and longitu-
dinal studies.
METHODS
We reviewed the literature in three stages. First, articles were
retrieved via online database searching, hand-searching reference
lists and cited reference searches (figure 2). The search was
limited to those that were published in English-language journals
from December 1982 (when the use of transcranial Doppler to
monitor cerebrovascular regulation was first described
25
)to
October 2013. Key articles retrieved via online databases and
hand-searching reference lists were also used for further cited ref-
erence search, and the results of cited reference searches were
further narrowed using relevant key words (figure 2). The review
of the references acquired from the database search results was
carried out by two of the authors (AJG and PS) independently. If
there was a disagreement between reviewers, a third reviewer was
to be sought to make the final decision; however, this was not
required for the current review. Next, we reviewed the titles and
abstracts of articles to assess eligibility for inclusion in this review.
Articles were regarded as relevant and warranting inclusion if
they were experimental studies examining cerebral vasoreactivity
via transcranial Doppler in concussed athletic samples. Papers
describing moderate to severe TBI were excluded. Studies were
included whether they were conducted acutely or postacutely (ie,
there were no restrictions placed on time since injury) and
whether or not they also used other outcome measures (eg, neu-
roimaging, symptom checklists, balance testing or neuropsycho-
logical testing). If there was uncertainty about whether a study
should be included based on the review of the title and abstract,
the full article was retrieved. Lastly, all retrieved articles were
independently assessed for quality using a standardised quality
assessment checklist selected for its generic comprehensiveness
and currency (table 1), as previously described.
26–29
RESULTS
A total of 2504 articles were identified using this search strat-
egy. Of the identified citations, 2498 were retrieved and
screened for eligibility. Eleven citations were excluded because
cerebral vasoreactivity was not used as a research method and
2303 were excluded on the basis that the human participants
were not athletes (ie, not sport-related concussion cases). Of
the remaining 181 excluded articles, 72 were excluded because
they were not research studies (eg, conference presentation,
abstract only, commentary) and 109 were excluded on the basis
that the study was conducted with animals. We were surprised
to find that there were only three articles on the possible rela-
tion between sports-related concussion and cerebral vasoreac-
tivity in humans.
Subsequently, we extracted from the identified studies the
data that pertain to (1) participant demographics (athletes and
control subjects), (2) characteristics of participants (sport, expos-
ure to concussion, concussive history), (3) methodological
details (technique and data collection), (4) time lapsed (immedi-
ate (minutes to hours), acute (1–14 days), subacute stage (2–4
weeks), prolonged and chronic stages (greater than 4 weeks))
and (5) results of the study (see tables 2 and 3for a summary of
results).
Overall, a total of 42 athletes and 33 ‘healthy athlete, neuro-
logically intact’control volunteers participated across the three
studies. One study examined the effects of repetitive blows to
the head from a career in boxing by using active non-concussed
boxers (ie, had not been diagnosed with a concussion recently)
who had recently (within the past 72 h) completed a sparring
session and compared these results with ‘physical-fitness’
matched non-boxing control athletes (ie, controls who had not
engaged in any form of contact sport that may have resulted in
head trauma and had not sustained a concussion).
30
The other
two studies were primarily comprised of hockey players
(85%
31
and 90%
14
). Among the two, one study did not
compare results with a control group,
31
while the other
recruited non-concussed athletes from the same university as
the concussed athletes were recruited.
14
Although the control
athletes in this latter study had not suffered a concussion in
the previous 2 months, there were no further details provided
on their concussion history.
Bailey et al
30
reported that boxers performed more poorly
on cognitive tests measuring attention, working memory, pro-
cessing speed, memory and executive function (eg, inhibitory
Table 1 Quality assessment rating results
Quality assessment rating criteria questions Bailey et al
30
Len et al
31
Len et al
14
1. Was the research question clearly stated? Yes Yes Yes
2. Was the selection of study participants/patients free from bias? Yes Yes Yes
3. Were study groups comparable? Yes No Yes
4. Was method of handling withdrawals described? N/A No N/A
5. Was blinding used to prevent introduction of bias? Yes No No
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s)
described in detail? Were intervening factors described?
Yes Yes Yes
7. Were outcomes clearly defined and the measurements valid and reliable? Yes Yes Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes Yes Yes
9. Were conclusions supported by results with biases and limitations taken into consideration? Yes Yes Yes
10. Is bias due to study’s funding or sponsorship unlikely? Yes Yes Yes
Overall quality rating Positive Neutral Positive
N/A, not applicable.
Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901 3
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control). This coincided with marked orthostatic hypotension,
cerebral hypoperfusion and corresponding cortical
de-oxygenation during orthostatic stress. Under normal circum-
stances, cerebral autoregulation (another component of cere-
brovascular regulation) can buffer against reductions in blood
pressure. However, it is possible that autoregulation may not
completely mitigate the impact of relatively large changes in
pressure consequent to orthostatic hypotension (due to impair-
ments in peripheral vascular control) on cerebral blood flow,
and this may partly explain the poor cognitive performance of
the boxers. Nonetheless, compared to controls, the boxers also
had marked differences on cerebral vasoreactivity, and there
was a significant negative correlation between the number of
rounds fought and reductions in cerebral vasoreactivity.
Consistent with Bailey et al,
30
Len et al
14
reported that while
there was no middle cerebral artery blood velocity difference
between injured athletes and controls at rest, under physio-
logical stress (ie hypocapnia (hyperventilation) and hypercapnia
(breath holding)), the concussed athlete group demonstrated
impairment in cerebral vasoreactivity (as assessed via repetitive
breath holding) compared to the controls. Lastly, in a second
study, Len et al
31
found that the reduction in the cerebral
vasoreactivity (assessed via repetitive breath holding) following
concussion tended to resolve over the first 5 days postinjury.
Therefore, while limited in number, available studies show
impairment in cerebral vasoreactivity after sports-related
concussion.
CONCLUSIONS
Available animal and in vitro studies suggest a link between
neurotrauma and impaired cerebral vasoreactivity.
Overproduction of endothelial NO after neurotrauma may
lead to impaired cerebral vasoreactivity; this might partially
underlie initial and exertion-induced symptoms after sports-
related concussion. Only three studies in humans explored
this link. The findings of these studies were reasonably con-
sistent with the animal and in vitro data. We highlight that
there are important population and methodological differ-
ences among the three studies. Two of the three studies exam-
ined athletes who had recently been diagnosed with a
sports-related concussion, and only two used control groups
(physical-fitness matched non-boxing control athletes, and
non-concussed adolescent and young adult contact sport ath-
letes). Moreover, two of the studies in sports-related concus-
sion
14 31
assessed cerebral vasoreactivity via repetitive 20 s
breath-holding. Breath holding provokes not only changes in
arterial carbon dioxide tension, but it also may change sympa-
thetic nerve activity, intrathoracic (thus, arterial blood) pres-
sure and cardiac output. Thus, it remains possible that the
reported impairments in cerebral vasoreactivity following
sports-related concussion may reflect mechanisms other than
cerebrovascular reactivity to elevations in CO
2
, such as cere-
bral autoregulation of neurovascular coupling that allow cere-
brovasculature to meet oxygen and glucose requirements of
the brain despite changes in blood pressure or metabolic
demand. Despite their limitations, these three studies provide
preliminary support for the possibility that cerebrovascular
responses to changes in arterial gases (ie, cerebral vasoreactiv-
ity) may be disrupted after sport-related concussion. The
pathophysiological mechanisms that underlie this disruption
are not yet clear. Although there are data suggesting that the
sympathetic nervous system restrains cerebrovascular
responses to CO
2
,
32
neither agonists nor antagonists of the
sympathetic system demonstrate any direct effect on
Table 2 Study characteristics
N Sex Time postinjury
References Athletes Controls M F Mean age (SD) Mean SD Symptoms Concussion definition Concussion history Level of play Sports Follow-up period (If any)
Bailey
et al
30
12 12 24 0 SRC: 27 (4.0)
Controls: 28
(4.0)
72 h
postsparring
NR Chronic Brain
Injury scale
scores; 8 mild,
4 moderate
NR (only bout and sparring
exposure)
Individual bout
history reported
P boxing (super
featherweight,
and light
heavyweight)
N/A
Len et al
31
20 0 16 4 19.7 (3.3) 2 days NR SCAT-2 symptom
score
A blow to the head causing
an alteration in mental
status and one or more of
the following symptoms:
headache, nausea,
vomiting, dizziness/balance
problems, fatigue, trouble
sleeping, drowsiness,
sensitivity to light or noise,
blurred vision, difficulty
remembering or difficulty
concentrating
Previous mTBIs
reported
A hockey,
snowboarding,
basketball, fight
2, 4 and 8 days
Len et al
14
10 21 28 3 21.4 (1.7) 4.5 1.1 SCAT-2 (all
asymptomatic)
NR Indication of a
history of concussion
but history NR
A hockey,
basketball
N/A
A, amateur; F, female; M, male; mTBIs, mild traumatic brain injuries; N/A, not applicable; NR, not reported; P, professional; SCAT-2, Sport Concussion Assessment Tool 2 SRC, sport-related concussed participants.
4 Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901
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vasoreactivity.
33 34
The role of myogenic mechanisms is also
unclear. In animals, calcium channel antagonists blunt the
vasoconstrictive effects of hyperventilation
35–37
and the vaso-
dilatory effects of hypercapnia.
38 39
In humans, however,
calcium channel antagonists have been reported to decrease
40
or have no effect on
41 42
vasoreactivity. Conversely, the cere-
bral vasoreactivity is decreased with pharmacological inhib-
ition of NO
43
and in populations with apparent endothelial
dysfunction.
44 45
For example, in healthy participants, NO
synthase inhibition via L-NMMA blunts the cerebral blood
flow response to hypercapnia and this can be reversed by
L-arginine.
43
Vasoreactivity is improved with acute L-arginine
administration in those with impaired vasoreactivity but not
in those with normal vasoreactivity.
44
Thus, the primary
physiological mechanism that underlies cerebral vasoreactivity
appears to be dependent on an intact endothelial NO system
(figure 1). Given that NO appears to be among the primary
biochemical mediators of vascular responses during the post-
traumatic phase (see Introduction section), these data further
reinforce the possible link between disruption in cerebral
vasoreactivity and sports-induced concussion.
We emphasise two important limitations. First, all three
studies reviewed above included adult volunteers. Yet, the
impact of concussion on cerebral vasoreactivity may differ
across the lifespan.
46
For example, Becelewski and Pierzchala
47
reported decreased vasoreactivity in younger but not in older
individuals following TBI. Thus, further research in paediatric
and adolescent populations is necessary. Second, deconditioning
during the rest period after initial injury, rather than (or in add-
ition to) the injury per se may impact mechanisms that underlie
cerebral vasoreactivity. In young healthy athletes, exercise train-
ing may not have appreciable effects on cerebrovascular control,
as a cerebrovascular function is at or near its peak capacity.
However, detraining can result in significant deficits in cerebral
regulatory control. This may be relevant to some athletes who
have sustained concussions because prolonged physical rest may
lead to serious deconditioning and resultant declines in cerebro-
vascular control (including vasoreactivity).
48
Thus, independent
of, or in addition to the primary cerebrovascular dysfunction
due to head trauma, prolonged rest after concussion leads to
deconditioning that may induce physiological changes in cere-
brovascular control.
Table 3 Cerebrovascular reactivity study characteristics
Study
CVR specifications, data acquisition and
analysis Other assessment methods used Study findings
Bailey et al
30
2 MHz-pulsed transcranial Doppler ultrasound
system (Multi-Dop X4; DWL Elektroniche
Systeme).
CO
2
measurement was performed in the supine
position with each participant’s head elevated to
30°. PETCO
2
was sampled from a leak-free mask
and analysed via capnography (ML 206;
ADInstruments). Following 10 min of breathing
room air, the inspirate was rapidly changed to
5% CO
2
with 21% O
2
and balanced nitrogen for
3 min. Following a 5 min recovery breathing
room air, participants hyperventilated at 15 bpm
for 3 min. From this, vasoreactivity was
calculated as the % increase/decrease in MCAv
from baseline per 1 mm Hg increase/decrease in
PETCO
2
recorded during the final 30 s (average
taken) of the hypercapneic/hypocapneic challenge
when steady-state was achieved
NP testing dCA (tight-cuff technique and transfer
function analysis) orthostatic tolerance (supine and
standing) mean arterial blood pressure (finger
photoplethysmography).
End-tidal CO
2
(capnography).Near-IR spectroscopy
(cortical oxyhaemoglobin concentration)
Vasoreactivity was reduced, resulting in a
lower range of blood flow responses.
Vasoreactivity was most marked in boxers
with the highest chronic traumatic brain injury
scores and correlated to the volume and
intensity of sparring during training.
These impairments coincided with more
marked cerebral hypoperfusion and
corresponding cortical de-oxygenation during
orthostatic stress
Len et al
31
A 2 MHz Doppler probe (Nicolet Companion III,
VIASYS Healthcare, Burlington, ON, Canada) was
placed over the right temporal window.
An electronic metronome was used during the
respiratory protocol to maintain proper cadence
during hyperventilation. Analysis of PETCO
2
was
conducted using a breath-by-breath expired gas
analysing system (Sensormedics vMax 2200,
VIASYS Healthcare), which was calibrated before
and after each test with primary standard gases
(16% O
2
,4%CO
2
, balance N
2
; 26% O
2
, balance
N
2
) and a 3.0 L factory calibrated syringe for
ventilation calibration
SCAT-2 Altered cerebral vasoreactivity following
concussion that resolves over approximately
the first 5 days of recovery.
Following a concussion:
▸Vasoreactivity is impaired in response to
respiratory stress;
▸The impairment may be resolved as early as
4 days post-injury
Len et al
14
A 1.6 MHz Doppler probe (Nicolet Companion III;
VIASYS Healthcare, Burlington, ON, Canada) was
placed over the right temporal window.
Breath-by-breath analysis of PETCO
2
was
conducted using an automated expired gas
analysing system (SensorMedics Vmax 2200;
VIASYS Healthcare)
SCAT-2 Normal cerebrovascular responses may be
impaired in the days immediately after
occurrence of concussion
5% carbon dioxide and controlled hyperventilation; CVR, cerebrovascular reactivity; CVRCO
2
, cerebrovascular reactivity to changes in carbon dioxide: dCA, dynamic cerebral
autoregulation; MCA, middle cerebral artery; MCAv, middle cerebral artery blow flow velocity; N
2
, nitrogen; NP, neuropsychological; O
2
, oxygen; PETCO2, end-tidal carbon dioxide;
SCAT-2, Sport Concussion Assessment Tool 2; vMCA, mean cerebral blow flow velocity.
Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901 5
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What are the new findings?
▸Although assessment of cerebrovascular responses to
changes in arterial gases (ie, cerebral vasoreactivity) after
neurotrauma is not a new concept; our review highlights
that this concept has been underexplored in athletes
suffering from sport-related concussion.
▸Three studies to date provide preliminary support for the
possibility that cerebral vasoreactivity may be impaired after
sport-related concussion.
▸Although the findings of human studies appear to be
consistent with the animal and in vitro data, the limited
number and scope of studies in humans highlight the urgent
need for more research.
Author affiliations
1
Centre for Translational Neuroscience and Mental Health, School of Medicine and
Public Health, University of Newcastle, Callaghan, New South Wales, Australia
2
Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital, Boston,
Massachusetts, USA
3
Department of Physical Medicine and Rehabilitation, Harvard Medical School,
Boston, Massachusetts, USA
4
Faculty of Health and Social Development, School of Health and Exercise Sciences,
Centre for Heart, Lung, and Vascular Health, Vancouver, British Columbia, Canada
5
University of British Columbia—Okanagan Campus, Vancouver, British Columbia,
Canada
6
Faculty of Health and Social Development, School of Health and Exercise Sciences,
University of British Columbia—Okanagan Campus, Vancouver, British Columbia,
Canada
7
Faculty of Health, Centre for Translation Neuroscience and Mental Health, School of
Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia
8
Centre for Translational Neuroscience and Mental Health, School of Medicine and
Public Health, University of Newcastle, Callaghan, New South Wales, Australia
9
Department of Physical Medicine and Rehabilitation, Harvard Medical School;
Spaulding Rehabilitation Hospital, MassGeneral Hospital for Children Sports
Concussion Program, & Red Sox Foundation and Massachusetts General Hospital
Home Base Program, Boston, Massachusetts, USA
Contributors AJG developed the concept, methodology, conducted the literature
search, established and reviewed the eligibility criteria of articles acquired from the
database search, and structured the review. He authored the initial drafts of the
manuscript, figures and tables. COT authored the background information pertaining
to the physiology and pathophysiology of cerebrovascular reactivity in animal models
as well as human studies. PNA and PvD also provided editing and comments on the
entire manuscript with particular focus on the background content regarding the
physiology and pathophysiology of cerebrovascular reactivity. PS reviewed the
eligibility of references acquired from the database search in addition to providing
expert input to the final draft of the manuscript. CRL provided expert input to the
final draft of the manuscript. GLI assisted with the development of the concept and
methodology. He also provided considerable editing and comments on all sections,
the figures and tables to finalise the manuscript.
Competing interests AJG has a clinical practice in neuropsychology involving
individuals who have sustained sports-related concussion (including current and
former athletes). He has received travel funding from the Australian Football League
(AFL) to present at the Concussion in Football Conference in 2013. Previous grant
funding includes the NSW Sporting Injuries Committee, the Brain Foundation and
the Hunter Medical Research Institute, supported by Jennie Thomas. GI has been
reimbursed by the government, professional scientific bodies and commercial
organisations for discussing or presenting research relating to mild TBI and
sport-related concussion at meetings, scientific conferences and symposiums. He has
a clinical and consulting practice in forensic neuropsychology involving individuals
who have sustained mild TBIs. He has received research funding from several test
publishing companies, including ImPACT Applications, Inc, CNS Vital Signs and
Psychological Assessment Resources (PAR, Inc). He is a co-investigator, collaborator,
or consultant on grants relating to mild TBI funded by several organisations,
including, but not limited to, the Canadian Institute of Health Research, Alcohol
Beverage Medical Research Council, Rehabilitation Research and Development
(RR&D) Service of the US Department of Veterans Affairs, Vancouver Coastal Health
Research Institute and Roche Diagnostics Canada.
Provenance and peer review Not commissioned; externally peer reviewed.
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Gardner AJ, et al.Br J Sports Med 2014;0:1–7. doi:10.1136/bjsports-2014-093901 7
Review
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review
sport-related concussion: a systematic
transcranial Doppler ultrasound in
Cerebrovascular reactivity assessed by
Peter Stanwell, Christopher R Levi and Grant L Iverson
Andrew J Gardner, Can Ozan Tan, Philip N Ainslie, Paul van Donkelaar,
published online December 1, 2014Br J Sports Med
http://bjsm.bmj.com/content/early/2014/12/01/bjsports-2014-093901
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