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S females increasingly participate in sports and other
high-risk activities, a greater understanding of the
role of patient sex in TBI outcome is needed.
20
In
1996, 2.4 million high school girls participated in school
sports, representing 39% of the high school athlete popula-
tion. This percentage represents an eightfold increase since
1971 when only 300,000 girls participated in high school
sports.
37
More recent data indicate that females now com
-
prise 42% of the athlete population at both the high school
and college levels.
42
Started in 1945, the annual survey of catastrophic foot-
ball injuries was expanded in 1982 through the establish
-
ment of the National Center for Catastrophic Sports Injury
Research.
30
The expansion was partially motivated by the
increasing participation of female athletes following Title
IX and by the lack of data on catastrophic injuries in female
athletes. Analysis of data collected between 1982 and 1999
revealed that female athletes suffered fatalities or sustained
permanent disabilities while participating in cheerleading,
volleyball, softball, gymnastics, and field hockey and that
more than 50% of these catastrophic injuries occurred due
to cheerleading. In addition, these studies demonstrated that
female athletes are at significant risk of sustaining sports
concussions or more serious brain injuries. Data gathered
by the National Collegiate Athletic Association Injury Sur
-
veillance System between 1997 and 2000 indicated that
female college athletes experience a greater number of con-
cussions during games than male college athletes, based on
both raw numbers and per game exposure.
11
These research-
ers found that female collegiate athletes in soccer and bas
-
ketball sustained significantly more concussions than their
male counterparts. Although several studies have been fo
-
cused on concussion following sports-related injury, none
has been undertaken to analyze possible sex-based dif
fer
-
ences in symptom severity
, constellation, or duration.
In the literature on mild head injury in which most trau-
ma is typically due to motor vehicle accidents, there are few
studies that do indicate a greater risk of poor outcome in fe
-
J Neurosurg 102:856–863, 2005
856
Sex differences in outcome following
sports-related concussion
DONNA K. BROSHEK, PH.D., TANYA KAUSHIK, PSY.D., JASON R. FREEMAN, PH.D.,
DAVID ERLANGER, PH.D., FRANK WEBBE, PH.D., AND JEFFREY T. BARTH, PH.D.
Department of Psychiatric Medicine, University of Virginia Health System, Charlottesville, Virginia;
HeadMinder, Inc., New York; Department of Psychiatry, Albert Einstein College of Medicine, New York,
New York; and Department of Psychology, Florida Institute of Technology, Melbourne, Florida
Object. Females comprise an increasing percentage of the athlete population across all age groups, and analysis of recent
literature reveals that they sustain more concussions in collegiate sports. Results of human and animal studies indicate that
females may have poorer outcomes after traumatic brain injury; however, no return-to-play guideline takes sex or other in-
dividual differences into account. In the present study the authors evaluated the influence of patient sex on objective neuro-
cognitive performance and subjective reporting of symptoms following sports-related concussion.
Methods. According to preseason baseline neurocognitive computerized testing in 2340 male and female high school
and collegiate athletes, individuals who sustained sports-related concussions (155 persons) were reevaluated using an alter-
nate form of the cognitive test. Sex differences in the magnitude of cognitive change from baseline levels and the subjec-
tive experience of symptoms were analyzed. To account for the possible protective effects of helmets, comparisons were
performed among females, males with helmets, and males without helmets; none of the female athletes wore helmets.
Female athletes had significantly greater declines in simple and complex reaction times relative to preseason baseline
levels, and they reported more postconcussion symptoms compared with males. As a group, females were cognitively
impaired approximately 1.7 times more frequently than males following concussions. Furthermore, females experienced
more objective and subjective adverse effects from concussion even after adjusting for the use of helmets by some groups
of male athletes (for example, in football).
Conclusions. Return-to-play decisions and concussion management must be objective and made on an individual basis,
including consideration of factors such as patient sex rather than relying on a one-size-fits-all guideline.
KEY WORDS • sports-related concussion • mild head injury • sex-based difference •
traumatic brain injury
A
J. Neurosurg. / Volume 102 / May, 2005
Abbreviations used in this paper: AAN = American Academy
of Neurology; ADHD = attention deficit hyperactivity disorder;
ANOVA = analysis of variance; CI = confidence interval; CRI =
Concussion Resolution Index; CRT = complex reaction time;
LOC = loss of consciousness; MANCOVA = multivariate analysis
of covariance; PS = processing speed; RCI = reliable change in-
dex; SE
diff
= standard error of difference; SRT = simple reaction time;
TBI = traumatic brain injury.
05_05_JNS.1.gls 4/21/05 1:06 PM Page 856
males. Females appear to have a greater likelihood of post-
concussion syndrome at the 1-month follow up,
4
a greater
incidence of depression following mild TBI,
21
and a greater
number of persisting symptoms 1 year after mild brain inju-
ry.
35
Although most individuals typically make a full recov-
ery from mild head injury, data from an epidemiological
study at the University of Virginia in the early 1980s re-
vealed that one third of the patients had persisting symp-
toms for at least 3 months.
32
This result underscored the
importance of studying the phenomenon of mild head in-
jury and identifying characteristics that might relate to de-
layed recovery. Patient sex may be one of the variables that
differentially affects recovery following mild head injury.
Among the literature on TBI are some notable studies
during which investigators examined the role of patient sex
on outcome. It is not surprising that these findings are in
-
consistent given that the demographic groups and the injury
severity level differ across, and even within, studies.
20,26
De-
spite the fact that males have approximately twice the risk
of females for sustaining a TBI,
9
data from a recent study in
patients with moderate and severe TBI demonstrated that
females had a mortality rate 1.28 times higher than that in
males.
26
Additionally, the likelihood of a poor outcome in
survivors was 1.57 times higher in females. A metaanal-
ysis on sex-based differences in outcome following TBI
revealed only nine studies in which the authors reported da-
ta according to sex.
20
Females demonstrated a poorer out-
come in 17 of 20 variables (85%) with a mean effect size
of !0.15. Other researchers, however, have reported that
females are more likely than males to return to school or
work after moderate to severe brain injury.
23
The as yet limited research on the association between
TBI and sex has yielded contrasting results. In the pediatric
literature, authors of two studies found that girls outper-
formed boys on measures of learning and memory within 1
year after TBI.
13,14
In contrast, authors of another study (data
unpublished) found that girls experienced greater dif
ficul
-
ties with executive function following significant brain in
-
jury
.
38
Girls have also been reported to be more vulnerable
to the long-term effects of cranial irradiation and chemo-
therapy.
39
Based on a review of the literature and their own
prospective research, Kraus and colleagues
26
have asserted
that future research in TBI should focus on the effects of sex
as well as the pathophysiological basis of differential out-
comes a
cross the sexes.
Research in animals to investigate sex as a factor in TBI
outcome has also yielded inconsistent results. Authors of
one study found that estrogen treatment in rats before inflic
-
ting an experimental fluid-percussion brain injury provid-
ed protective ef
fects in males and exacerbated the injury in
females.
16
Female rats have also been noted to have high-
er mortality rates following fluid-percussion injury
. In hy
-
ponatremic conditions, depressed oxygen use and cerebral
blood flow were observed in female rodents.
25
Data from
these animal studies indicated a pathophysiological basis
for the poorer outcome in the female sex following TBI.
More recent research, however, has revealed that estrogen
provided a neuroprotective effect, resulting in a better out-
come in female mice compared with that in the male ones
following experimental TBI inflicted using the murine im-
pact–acceleration head injury method.
27
In addition, male
mice had a 20% mortality rate, whereas no death occurred
in the female mice.
A principal limitation of the human studies on concus-
sion and TBI is the lack of preinjury data on patients, which
especially limits the scope of research on sex-based dif-
ferences in cognitive functions. For example, results of one
recent study revealed significant sex differences between
male and female college athletes, with females demonstrat-
ing faster and more accurate perceptual motor performance
and better verbal fluency.
3
6
Sex differences in neuropsy-
chological test performance in healthy athletes may in turn
obscure sex differences in postconcussion cognitive func-
tioning and recovery. Barth and colleagues
2
pioneered the
principle of obtaining baseline preseason data on athletes
prior to injury to increase the scope of scientific inquiry into
mild head injury. This methodology, termed the “Sports-as-
a-Laboratory model,” is widely accepted as the gold stan
-
dard for identifying and managing sports-related concus
-
sions and is now common in professional sports and college
athletics.
3,10,15
In previous studies
17
we have demonstrated
that the use of RCI scores, a means of appraising injured
athletes individually posttrauma compared with their own
unique baseline scores, is a superior method of determining
and quantifying the severity of postconcussion cognitive
symptoms. W
e therefore hypothesized that a greater under-
standing of potential sex dif
ferences in sports-related con-
cussion would be possible by using a baseline model and
RCI scores.
Clinical Material and Methods
Cognitive Performance Measures
The CRI, a web-based, brief computerized neurocogni-
tive assessment tool, consists of six cognitive subtests that
resolve to three summary speed factors: SRT, CRT, and PS.
The CRI is sensitive to decreases in memory, reaction time,
and speed of information processing immediately following
concussion and until resolution of such typically transient
neurocognitive dysfunction.
17
All subtests were adminis-
tered before trauma and again at each posttrauma evalua-
tion. Statistical analyses of injured athletes’ test performan-
ces are adjusted for test–retest reliability and for practice
ef
fects. Alternate forms are automatically provided.
When obtaining baseline measures, the subtests were
preceded by a short questionnaire designed to gather demo-
graphic information, concussion history, and other perti-
nent medical information that might be useful in return-to-
play decision making. Following head trauma, the cognitive
subtests were preceded by questions about the athlete’s
symptom presentation immediately following injury (LOC,
retrograde amnesia, dizziness, headache, and confusion/dis-
orientation), which were answered by the athletic trainer or
team physician who witnessed the injury, and the presence
and intensity of postconcussion symptoms at testing time
(headache, fatigue, memory problems, concentration dif
fi
-
culty
, nausea, and so forth), which were rated by the athlete.
All symptoms were surveyed at each postconcussion as
-
sessment. Although many symptoms are often recorded as
absent, mild, moderate, or severe, for our purposes these
symptom scales were truncated to the dichotomy of present
or absent.
Participants and Procedures
Baseline CRI assessments were group administered in
J. Neurosurg. / Volume 102 / May, 2005
Sex differences in outcome from sports-related concussion
857
05_05_JNS.1.gls 4/21/05 1:06 PM Page 857
computer labs via web-enabled desktop computers to ath-
letes in contact sports at several US high schools and col-
leges as part of an ongoing research project. Institutional re-
view board approval was obtained, as was informed consent
from all adult athletes and from parents of athletes youn-
ger than 18 years of age. Following a concussion, athletes
underwent follow-up tests according to the clinical judg-
ment of the athletic trainer, team physician, or psychologist
in charge of care, typically at 1- to 2-day intervals, until all
symptoms resolved. For the current analysis, only data col-
lected during the first follow up were used for comparisons
with baseline performance levels. No other performances
were included in the analyses.
Results
One hundred fifty-five athletes sustained concussions as
determined at the time of the injury by an athletic trainer or
physician using the Standardized Assessment of Concus
-
sion
29
and/or a symptom inventory. Of these athletes, 117
(75.5%) were male and 38 (24.5%) were female. Baseline
cognitive performances on the CRI did not differ according
to patient sex, ethnicity, age (high school compared with
college), or history of learning disability or ADHD. Be-
cause analysis of postconcussion performances on the CRI
according to patient sex was our interest, possible con-
founds were examined. Ethnic representation (Caucasian
compared with non-Caucasian) differed significantly ac-
cording to sex ("
2
= 8.4, p = 0.004), with Caucasians being
overrepresented in the female group (86.8 compared with
61.5%). Note, however, that results of ANOVA revealed no
difference between ethnic groups on the CRIs at the initial
postconcussion assessment, indicating that potential differ-
ences based on sex would not be confounded by differences
in the ethnic make-up of the two groups. A self-reported
history of a learning disability or ADHD also differed sig-
nificantly according to sex (
"
2
= 6.35, p = 0.012), with such
diagnoses being overrepresented in the male group (19.7
compared with 2.6%). Results of ANOVA revealed signifi-
cant differences in postconcussion performances according
to learning disability or ADHD, with those affected by such
disabilities performing significantly slower on two of the
three CRI speed indices (CRT: F = 6.52; df = 1, 153 [sam-
ple size minus two conditions in ANOVA]; p = 0.012
and PS: F = 8.82; df = 1, 153; p = 0.003). Because persons
with a learning disability or ADHD were disproportionate-
ly male, this group of 24 athletes was excluded from further
analyses to avoid confounding findings on sex and con-
cussion.
Thus, of the 131 athletes studied further, 94 (71.8%) were
males and 37 (28.2%) were females. There was an approx-
imately equal number of high school and college athletes
(47.3 compared with 52.7%, respectively), although women
were overrepresented in the high school group (64.9 com-
pared with 35.1%). Similarly
, although the mean age for the
entire group was 18.72 # 2.1 years (standard deviation,
range 14.3–23.8 years), males were significantly older than
females (19.2 compared with 17.5 years; F = 17.9; df = 1,
129; p
$ 0.001). Because of the age discrepancy, analyses
of age and age-based sex differences were performed for
self-reported symptoms and CRI baseline, follow up, and
baseline follow-up dif
ference scores, with no significant
age or age/sex interactions identified. Sixty-nine percent of
the athletes identified themselves as Caucasian, 23% as Af-
rican-American, and 8% as other. (Note that results of an
ANOVA indicated that in the group excluded for learning
disability and ADHD, there was no difference in baseline
CRI scores based on sex, ethnicity
, or age, thus revealing
that the index is not ethnicity biased.)
In 54% of the athletes,
the incurred injury represented the first ever concussion, in
26% the second, in 11% the third, and in 9% the fourth or
more; these frequencies did not differ significantly accord-
ing to sex. Approximately 75% of the males sustained con-
D. K. Broshek, et al.
858
J. Neurosurg. / Volume 102 / May, 2005
TABLE 1
Summary of sports activities in 131 concussed
athletes grouped according to sex
Group No. of Patients (%)
females
soccer 13 (35.1)
field hockey 7 (18.9)
lacrosse 5 (13.5)
basketball 4 (10.8)
cheerleading 3 (8.1)
other 5 (13.5)
males
football 68 (72.3)
lacrosse 6 (6.4)
wrestling 6 (6.4)
other 14 (14.9)
TABLE 2
Two indices of concussion severity
grouped according to sex
No. of Patients (%)
Grading Criteria Males Females
Cantu grade
I 45 (47.9) 15 (40.5)
II 22 (23.4) 10 (27.0)
III 27 (28.7) 12 (32.5)
AAN grade
I 10 (10.6) 3 (8.1)
II 67 (71.3) 32 (81.9)
III 17 (18.1) 4 (10.8)
FIG. 1.
Bar graph demonstrating mean RCI scores on CRIs to
-
gether with 95% CIs on follow up.
Shaded bars represent men;
white bars represent women. * p $ 0.05.
05_05_JNS.1.gls 4/21/05 1:06 PM Page 858
cussions while playing football and 33% of the females did
so while playing soccer. Table 1 details the sports activities
by sex. Males underwent their first postinjury assessment
sooner than did females (mean 2.8 compared with 3.8 days,
respectively; Mann–Whitney
"
2
= !2.3, p = 0.021).
Severity of concussion was determined using two meth-
ods, the AAN
31
and Cantu grading criteria,
7,8
which were ap-
plied to each case based on contemporaneous reports by the
athletic trainer or team physician who had witnessed the in-
jury and was involved in the athlete’s follow-up care. Ta-
ble 2 depicts concussion severity graded according to both
AAN and Cantu criteria stratified by sex. There was no dif-
ference between males and females in injury severity based
on either of these criteria, although males did experience
LOC approximately twice as frequently as females (18
compared with 11%, respectively). In keeping with our pre-
vious research, LOC did not correlate significantly with any
outcome variable.
To assess differences in postconcussion CRI performance
relative to baseline levels, RCI scores were calculated for
the three speed factors in each athlete according to the
following formula: [(x
2
! x
1
)/SE
diff
] (!1).
17
By multiply-
ing the RCI z score by !1, slower speeds following inju-
ry appeared as negative z scores, and faster postinjury per-
formances as positive ones. T
o test whether there were
differences in postconcussion objective and self-reported
sequelae according to sex, a MANCOVA was performed
using sex as the independent variable, RCI scores for each
of the three CRI speed factors and total number of symp-
toms as dependent variables, and time to follow up as a co-
variate. The time to follow up correlated significantly with
the extent of the cognitive performance decrease compared
with baseline levels regardless of sex; in fact, longer time
periods were associated with more minor decreases. Patient
age, another variable that dif
ferentiated the two groups, did
not correlate with the extent of the performance decrease
compared with baseline, and so was not included as a co-
variate.
The overall model was significant for sex (Hotelling T =
0.076, F = 2.36, p = 0.05). Group comparisons were signif-
icant for CRT (F = 5.13, p = 0.025), SRT (F = 6.20, p =
0.014), and number of symptoms (F = 5.41, p = 0.022), but
not for PS (F = 1.41, p = 0.238). Females consistently expe-
rienced greater declines in cognitive function and dem-
onstrated more symptoms. Figure 1 depicts the mean RCI
z scores and 95% CIs for the two sex groups, adjusted
for time to follow up, illustrating the greater performance
declines on the CRI factors in females. In addition to the
three CRI RCI scores, the number of symptoms reported by
athletes at the time of the initial postconcussion evaluation
was treated as a dependent variable reflective of the se-
verity of postconcussion sequelae. The frequency of cogni-
tive impairment based on sex is presented in Fig. 2. Al-
though women reported concentration problems, fatigue,
lightheadedness, and seeing flyspecks significantly more
often than did men, the constellation of symptoms were re-
markably similar between the sexes. Figure 3 depicts the
mean number of symptoms together with 95% CIs reported
by males compared with those reported by females.
To determine the clinical significance of these differen-
ces, athletes were classified as “cognitively impaired” if any
one of their RCI scores indicated a decrease of more than
1.645 SE
diff
(p % 0.05) from baseline levels at the postcon-
cussion assessment. A z score of !1.645 was chosen as the
threshold for determining a significant decline from base-
line levels because a decrease of this size is associated with
a probability value of 0.05. Approximately 57% of the fe
-
males were cognitively impaired compared with 33% of the
males, which represented a significantly greater frequency
(
"
2
= 6.27, p = 0.012).
W
e hypothesized that females might experience more
J. Neurosurg. / Volume 102 / May, 2005
Sex differences in outcome from sports-related concussion
859
FIG.
2. Bar graph depicting self-reported symptoms on follow up according to patient sex.
S
haded bars
,
males;
w
hite
bars
, females. * p $ 0.05.
FIG. 3. Bar graph exhibiting the mean number of symptoms re-
ported on follow up according to patient sex together with 95% CIs.
Shaded bars, males; white bars, females; p $ 0.05.
05_05_JNS.1.gls 4/21/05 1:06 PM Page 859
symptoms and demonstrate significant declines in cognitive
function more frequently than males because few females
wore headgear of any type, whereas most male athletes
were football players, who were equipped with helmets.
Therefore, we divided the male athlete group into those
with and those without helmets and performed a MANCO-
VA using females (all of whom were unhelmeted), unhel
-
meted males, and helmeted males as the independent vari-
able, the RCIs of the three CRI factors and the number of
symptoms as dependent variables, and the time to follow
up as a covariate. The overall model was significant for the
patient sex helmet variable (Hotelling T = 0.146, F = 2.25,
p = 0.03). Group comparisons were significant for CR
T
(F = 4.00, p = 0.02), SRT (F = 3.11, p = 0.05), and num-
ber of symptoms (F = 3.74, p = 0.03). Results of pairwise
comparisons indicated that females demonstrated signifi
-
cantly slower response speed on the CRT and PS, a mar-
ginally slower SRT, and more symptoms compared with
those in unhelmeted males.
Females also had significantly
slower response speed on the SRT and significantly more
symptoms than those in helmeted males, whose perfor-
mance generally occupied a middle ground between the two
groups of unhelmeted athletes. Figure 4 depicts the mean
RCI z scores and 95% CIs for the three groups, adjusted for
time to follow up, illustrating the more severe declines ex
-
perienced by females on the CRI factors. Figure 5 depicts
the mean number of symptoms with 95% CIs reported by
females, males without helmets, and males with helmets.
To determine the clinical significance of these differen-
ces, athletes were classified as cognitively impaired if any
one of the RCI scores indicated a decrease of more than
1.645 SE
diff
(p % 0.05) from baseline levels at the post-
concussion assessment. Table 3 shows that more than twice
as many unhelmeted females (57%) were cognitively im
-
paired compared with unhelmeted males (28%), and that
helmeted males experienced impairment in 34% of the
cases. The distribution of these frequencies was significant
(
"
2
= 6.52, p = 0.038). Of additional interest, the Mantel–
Haenszel linear-by-linear association value of 5.68 (p =
0.017) indicated that, clinically, the same linear relationship
as that observed in the ANOV
As was present.
Discussion
Since Title IX was passed in 1972, females have been
participating in sports in increasing numbers. Surprisingly,
the present study appears to be the first effort objectively to
compare neurocognitive sequelae in male and female ath-
letes following sports-related concussion. In this prospec-
tive study in high school and college athletes, we examined
the relationship of patient sex to the severity of cognitive
decline and the number of self-reported symptoms. First,
we identified a significantly more severe decline in females
on measures of SRTs and CRTs, relative to preseason base-
line levels. Second, females self-reported significantly more
symptoms following concussion compared with males.
These sex dif
ferences were evident when comparing males
and females in terms of both the degree of cognitive change
from baseline levels and the frequencies of impaired cog-
nitive performance. In the former case, the decreases in
female cognitive performance levels were approximately
1 SE
diff
greater than those in males. In the latter case, fe-
males were cognitively impaired approximately 1.5 times
more often than males following concussion (57 compared
with 37%, respectively).
These findings did not appear to be
due to dif
ferences in injury severity
, patient age or eth-
nicity, baseline performance levels, or time to follow up. In
fact, females demonstrated significantly greater changes
from baseline cognitive performance and significantly more
symptoms following concussion despite being evaluated a
mean of 24 hours later than males.
Patient age, which did differ between men and women in
our sample, was not significantly correlated with CRI base-
line, follow-up, or baseline follow-up difference scores or
with the number of self-reported symptoms. Furthermore,
D. K. Broshek, et al.
860
J. Neurosurg. / Volume 102 / May, 2005
FI
G
. 5. Bar graph demonstrating the mean number of symptoms
as well as CIs reported on follow up by males with helmets
(dark
gray bars)
, males without helmets (light gray bars), and females
(white bars). Females had more symptoms than males without hel-
mets, p = 0.01; females had more symptoms than males with hel-
mets, p = 0.05.
F
IG. 4. Bar graph exhibiting mean RCI scores on CRIs together
with 95% CIs on follow up. *Scores in females (white bars) were
lower than those in males without helmets (light gray bars), p $
0.01; scores in females were lower than those in males with helmets
(dark gray bars), p $ 0.15. **Scores in females were lower than
those in males without helmets, p $ 0.15; scores in females were
lower than those in males with helmets, p
$ 0.05. ***Speeds in fe-
males were lower than those in males without helmets, p $ 0.05.
05_05_JNS.1.gls 4/21/05 1:06 PM Page 860
there was no significant interaction between patient age and
sex for these same scores and symptoms.
An additional hypothesis and a possible explanation for
our findings was that helmets might provide protection for
male athletes, the majority of whom were football players;
however, women experienced more significant sequelae
than helmeted males and suffered more serious symptoms
than males without helmets. Among all unhelmeted ath-
letes, females were more than twice as likely as males to
experience cognitive impairment following concussion (57
compared with 28%, respectively). Based on these data, it
seems clear that females experience more objective and
subjective adverse effects of concussion even after adjusting
for the wearing of protective head gear.
Another possible explanation for the sex-based differ-
ences in our study may be related to the style of play or lev-
el of aggressiveness inherent in different sports. Sports
played by males are typically assumed to be more aggres-
sive, which is part of the reason helmets are often required
even though the same sport played by females does not (for
example, lacrosse), although this theory may not be ac-
curate. Future investigators must examine the sex differen-
ces in the on-field behavior as well as the mechanisms of
sports-related concussion.
From a physiological perspective, sex differences in hor-
monal systems, cerebral organization, and musculature may
partially explain our findings. The literature provides con-
trary findings regarding the potential neural protection af-
forded by female gonadal hormones in animals. Estrogen
may be either a protective or a detrimental factor depending
on the study reviewed, whereas progesterone seems to func-
tion broadly to reduce post-TBI neural impairment.
34
The
varying results may be a reflection of study design, includ-
ing whether animals were exposed to a fluid-percussion in-
jury, a focal-impact injury, or an impact-acceleration injury.
In addition, authors of a recent study, which demonstrated
that estrogen provided a neuroprotective effect in female
mice, did not manipulate levels of estrogen but simply ex-
amined differences in recovery based on sex.
27
In contrast,
other researchers who found that estrogen exacerbated brain
injuries in female rats and provided protective effects in
male rats actually treated the rats with supplemental estro
-
gen 4 hours prior to inducing head injury.
16
These discrepant
findings may be partially due to the differential impact of
exogenous compared with endogenous estrogen in TBI. Fu-
ture research in humans should be aimed at examining fluc
-
tuations in hormonal levels to determine whether there are
cyclical periods of greater vulnerability or greater neuropro
-
tection in concussed female athletes that might affect neu-
rocognitive outcome, the recovery curve, and the duration
of follow up.
The fact that sex may differentially determine TBI in-
cidence, severity, and symptom resolution should not be
surprising. There are considerable sex-based differences in
neural anatomy and physiology, cerebrovascular organiza-
tion, and cellular response to concussive stimuli. For exam-
ple, cortical neuronal densities are greater in males, where-
as neuropil numbers are greater in females.
12
Blood flow
rates are greater in females than in males,
19
and females
exhibit a greater basal rate of glucose metabolism.
1
The lat-
ter two functional differences may well exist in support
of the increased ionic flux across the greater membrane ar-
ea suggested by the higher neuropil count. To the extent
that brains in females may have greater metabolic demands,
a more intense and prolonged symptom response to mild
TBI may reflect an exacerbated, or at least a more broad-
ly distributed, metabolic cascade as described by Giza and
Hovda.
22
Specifically, the typical decrease in cerebral blood
flow along with the increased glycemic demands caused by
TBI may interact with the already increased demands and
lead to greater impairment in females than in males.
Although there was no significant sex-based difference in
performance on baseline neurocognitive testing, one of the
limitations of this study is that no inference can be made
about baseline sex differences in intellectual ability or cog-
nitive reserve based on the test administered. It is possible
that any differences might have affected the observed sex
effect in concussion outcome. Furthermore, we only ex-
amined postconcussive sex differences among athletes for
whom we had baseline neurocognitive data, perhaps result-
ing in selection bias. Our study design of obtaining baseline
data in large numbers of athletes in high-risk sports, howev-
er, limits the impact of this confound. In addition, the length
of time between concussion and follow-up neurocognitive
evaluation was not standardized among all the data collec-
tion sites. Interestingly, although female athletes tended not
to be followed up as quickly—thus allowing additional time
for recovery—they still demonstrated poorer outcomes.
Data in this study provide important information for the
clinical management of concussion. Note that although fe
-
males experienced more severe postconcussion symptoms,
males were followed up significantly sooner (by approxi-
mately 24 hours), perhaps indicating that injuries in females
may not be taken as seriously. Alternatively, this finding
may reflect less aggressive follow-up testing based on the
perceived severity of initial symptoms and conservative
management of the recovery process (that is, not perform
-
ing cognitive challenges while the patient remains symp
-
tomatic). Results of previous studies have revealed a ten
-
dency for females to report more symptoms following head
injury.
6,35
Those in the medical profession often interpret
such reports as an indication that women complain more de-
spite having fewer objective symptoms. Based on objective
test findings, we assert that females do in fact experience
more severe postconcussion symptoms than males and that
poorer outcomes are not simply due to culturally based sex
dif
ferences in reporting symptoms. Such findings may be
critical in countering the documented reduced levels of
post-TBI services provided to women.
5
Because more severe objective declines in reaction time
and processing speed mirrored more severe subjective
symptoms, data in this study serve to caution against dis-
missing symptom reports following TBI. Although post-
J. Neurosurg. / Volume 102 / May, 2005
Sex differences in outcome from sports-related concussion
861
TABLE 3
Frequency of cognitive impairment on
postconcussion follow up in 131 athletes*
No. of Patients (%)
Group w/o Cognitive Impairment w/ Cognitive Impairment
unhelmeted males 13 (72.2) 5 (27.8)
helmeted males 50 (65.8) 26 (34.2)
unhelmeted females 16 (43.2) 21 (56.8)
* "
2
= 6.52, p = 0.038.
05_05_JNS.1.gls 4/21/05 1:06 PM Page 861
concussion syndrome symptoms may represent nonneu-
rological factors,
24
clearly such is not universally true.
Although male athletes were more likely to experience
LOC at the time of concussion, which may have been inter-
preted as reflecting a more severe injury, women demon-
strated worse cognitive dysfunction on follow up. This find-
ing provides additional evidence for the growing literature
indicating that LOC is not a good predictor of outcome.
1
0,18,28
Again, our results call into question the return-to-play crite-
ria (such as those of the AAN) that rely heavily on LOC in
grading concussion. Although current investigators still use
LOC as the only measure of severity,
33
many authors have
pointed out the shortcomings in this approach.
8,40,41
Al-
though, intuitively, the approach of using baseline neuro-
cognitive testing to detect changes following concussion ap
-
pears more sensitive than traditional grading scales, we did
not perform a direct comparison of these two approaches in
the present study
. It remains a critical area for future re-
search.
Conclusions
Female athletes had significantly more severe declines
on SRTs and CRTs relative to preseason baseline levels
and they reported more postconcussion symptoms com-
pared with males. Furthermore, females were cognitively
impaired approximately 1.7 times more often than males
following concussion. Females experienced more objec-
tive and subjective adverse effects of concussion even af-
ter adjusting for the use of helmets by some groups of male
athletes (for example, those playing football). Given the
potential for sex differences and other as yet unidentified
variables that affect concussion severity and recovery
, the
importance of individualized concussion management can-
not be overstated. Data collected on the preseason baseline
administration of computerized or paper-and-pencil neuro-
psychological measures that are validated for detecting con-
cussion for comparison with individual postconcussion da-
ta represent the gold standards for identifying the degree of
cognitive decline and recovery. Medical care and return-to-
play decisions should be based on a comparison between
pre- and postinjury neurocognitive data and the recovery
curve of each individual athlete rather than relying on one-
size-fits-all return-to-play criteria.
Disclosure
Drs. David Erlanger and Tanya Kaushik are employed by Head-
Minder, Inc., which is the publisher of the CRI. Dr. Erlanger also
holds a significant number of shares in the company.
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Accepted in final form January 24, 2005.
Address reprint requests to: Donna K. Broshek, Ph.D., Neuro-
psychology Laboratory, Box 800203, University of Virginia School
of Medicine, Charlottesville, Virginia 22908–0203. email: broshek
@virginia.edu.
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