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ORIGINAL ARTICLE CLINICAL STUDIES
Diagnosing Level of Consciousness:
The Limits of the Glasgow Coma Scale Total Score
Yelena G. Bodien,
1,2,
*
,
** Alice Barra,
1,3,4,
** Nancy R. Temkin,
5,6
Jason Barber,
5
Brandon Foreman,
7
Mary Vassar,
8
Claudia Robertson,
9
Sabrina R. Taylor,
8
Amy J. Markowitz,
8
Geoffrey T. Manley,
8
Joseph T. Giacino,
1,
***
Brian L. Edlow
2,10,
***; and the TRACK-TBI Investigators****
Abstract
In nearly all clinical and research contexts, the initial severity of a traumatic brain injury (TBI) is measured
using the Glasgow Coma Scale (GCS) total score. The GCS total score however, may not accurately reflect
level of consciousness, a critical indicator of injury severity. We investigated the relationship between GCS
total scores and level of consciousness in a consecutive sample of 2455 adult subjects assessed with the
GCS 69,487 times as part of the multi-center Transforming Research and Clinical Knowledge in TBI (TRACK-
TBI) study. We assigned each GCS subscale score combination a level of consciousness rating based on pub-
lished criteria for the following disorders of consciousness (DoC) diagnoses: coma, vegetative state/
unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state, and pres-
ent our findings using summary statistics and four illustrative cases. Participants had the following characteris-
tics: mean (standard deviation) age 41.9 (17.6) years, 69% male, initial GCS 3–8 =13%; 9–12 =5%; 13–15 =82%.
All GCS total scores between 4–14 were associated with more than one DoC diagnosis; the greatest variability
was observed for scores of 7–11. Further, a wide range of total scores was associated with identical DoC diag-
noses. Importantly, a diagnosis of coma was only possible with GCS total scores of 3–6. The GCS total score does
not accurately reflect level of consciousness based on published DoC diagnostic criteria. To improve the classi-
fication of patients with TBI and to inform the design of future clinical trials, clinicians and investigators should
consider individual subscale behaviors and more comprehensive assessments when evaluating TBI severity.
Keywords: behavioral assessments; consciousness; diagnosis; prognosis; Glasgow Coma Scale; traumatic brain
injury
Introduction
The Glasgow Coma Scale (GCS), developed in 1974 by
Teasdale and Jennett,
1
is the most widely used behav-
ioral measure to assess the severity of acute traumatic
brain injury (TBI).
2,3
The scale’s simplicity and rapid
assessment approach has led to its international adoption for
both diagnostic and prognostic
4
applications in pre-
hospital, emergency department (ED), and intensive care
unit (ICU) settings. The GCS has been designated a core
TBI Common Data Element
5
by the National Institute of
1
Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
2
Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
3
Coma Science Group, GIGA Consciousness, University of Liege, Lie
`ge, Belgium.
4
Centre du Cerveau (C2), University Hospital, Lie
`ge, Belgium.
5
Department of Neurological Surgery and
6
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
7
Department of Neurology & Rehabilitation Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
8
Department of Neurological Surgery, University of California, San Francisco, California, USA.
9
Department of Neurosurgery, Baylor College of Medicine, Ben Taub Hospital, Houston, Texas, USA.
10
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
**Co-first authors, ***Co-last authors, ****The TRACK-TBI Investigators may be found at the end of this article.
*Address correspondence to: Yelena G. Bodien, PhD,Massachusetts General Hospital,101 Merrimac Street, Suite 300,Boston, MA 02114,USA E-mail: ybodien@
mgh.harvard.edu
*Correction added on January 7, 2022 after first online publication of November 23, 2021: In the corresponding author address there was a typo in the street name.
The street name has been corrected to ‘Merrimac.’
Journal of Neurotrauma
38:3295–3305 (December 1, 2021)
ªMary Ann Liebert, Inc.
DOI: 10.1089/neu.2021.0199
3295
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Neurological Disease and Stroke and is commonly used in
clinical trials both as a criterion for subject inclusion and as
an approach for subject stratification.
6
The GCS is scored based on behaviors observed across
three subscale scores—eye-opening (score range 1–4),
verbal (score range 1–5), and motor (score range 1–6)—
that are summed to provide a total score ranging from
3–15.
7
The total score is intended to reflect severity of in-
jury, with scores of 3–8 indicating a severe injury, 9–12
a moderate injury, and 13–15 a mild injury. Moreover,
GCS total scores of 3–8 are often used to define coma.
8
Despite its widespread use, GCS administration and scor-
ing is not standardized, and its psychometrical strength
is moderate.
3,9
While there is a relationship between GCS
total score and prognosis,
7,10
this relationship is strongest
for predicting death in large population studies
11
but not
for predicting morbidity or functional outcome at the in-
dividual patient level.
12
Cognizant of its limitations, the original developers of
the GCS wrote in 1978 that, although total scores may
have prognostic utility, important information about cur-
rent function and the potential for recovery is lost when
reporting a GCS total score rather than individual com-
ponent scores.
7
In 1983 and again in 2014, Teasdale and
colleagues
2,13
reaffirmed the importance of specifying the
score for each of the three subscales and that failure to do
so could limit the ability to detect changes in consciousness.
Multiple studies have found that individual subscale
scores are more diagnostically
14
and prognostically
15
rel-
evant than the total score. Moreover, different combina-
tions of subscales that sum to the same total score are
associated with variable mortality rates.
16
The implica-
tion of these findings spans across clinical and research
settings where GCS scores are often further collapsed
into three broad categories of mild, moderate, and severe
TBI. This coarse classification may mischaracterize indi-
vidual patient prognosis, as evidenced by some ‘‘severe’’
patients having a favorable outcome
17
and some ‘‘mild’’
patients having an unfavorable outcome.
18
From a clinical trial design perspective, reliance on GCS
total scores may contribute to improper inclusion and strat-
ification of subjects, leading to heterogenous study groups,
lack of statistical robustness, inaccurate interpretation of
findings, and ultimately trial failure.
6
Despite the evidence
for using GCS subscale scores rather than a total score,
GCS total scores remain the most common metric for
establishing TBI severity and stratifying study subjects.
6
Since the development and dissemination of the GCS,
the diagnostic framework for classifying level of con-
sciousness has evolved to be more precise. A definition
of the minimally conscious state (MCS) was published
in 2002 by the Aspen Neurobehavioral Conference Work-
group.
19
MCS was further subdivided into MCS+and
MCS- based on presence or absence of language function,
respectively.
20
Distinguishing between the vegetative
state/unresponsiveness syndrome (VS/UWS), MCS- and
MCS+diagnoses increases prognostic precision.
20–22
The GCS was not designed, however, to differentiate
these DoC states and lacks assessment of items such as visual
pursuit and fixation that are crucial for detecting conscious-
ness.
23,24
In fact, the GCS has been estimated to have a false
negative rate of 38% for detection of consciousness.
24
It fol-
lows that, in some patients, neither GCS total scores nor
subscale scores may characterize injury severity accurately.
The association between GCS total scores and the current
diagnostic criteria for level of consciousness is unknown.
We identified all potential combinations of GCS total scores
and used published diagnostic criteria for VS/UWS, MCS-,
MCS+,
19,20
and the post-traumatic confusional state
(PTCS)
25
to match each GCS score combination with a
level of consciousness. We then evaluated the observed in-
cidence of each GCS combination in the Transforming
Research and Clinical Knowledge in TBI (TRACK-TBI)
study. Finally, we provide case studies illustrating the diag-
nostic discrepancies that result from using GCS total scores.
Methods
Participants
TRACK-TBI is an 18-site observational study aimed at
improving phenotypic accuracy and outcome precision
for patients with TBI. Subjects at participating sites are
enrolled within 24 h of injury and followed up to 12
months if they meet the following criteria: documented
TBI, computed tomography (CT) scan, and no significant
polytrauma that would interfere with follow-up assess-
ment (for full inclusion criteria, see the TRACK-TBI
website).
26
The Institutional Review Board of each site
approved the study protocol, and all subjects or surrogates
provided written informed consent to participate.
Acute hospitalization data elements, including GCS
scores obtained in the field, ED, ICU, and on the hospital
ward, were abstracted from medical records by research
staff and documented in an electronic database. The GCS
scores were available for the first five days of hospitaliza-
tion and for the entire duration that intracranial pressure
was monitored.
Of the 2552 subjects (‡17 years old) enrolled in
TRACK-TBI from 2014–2018, we excluded (1) subjects
with no GCS scores (n=28); (2) subjects for whom all
GCS scores were confounded by periorbital swelling, in-
tubation, and/or paralysis (n=68); and (3) subjects for
whom data errors (e.g., GCS date preceded injury date)
could not be resolved (n=1). The final sample included
2455 subjects with at least one unconfounded GCS
score (Supplementary Fig. S1).
Collectively, these subjects were assessed with the GCS
69,487 times. Periorbital swelling, intubation, and/or pa-
ralysis were documented in 30,139 of the 69,487 GCS
scores, leaving 39,348 unconfounded GCS scores for
the primary analysis. Intubation was the most common
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confounding factor and was documented in 28,902 GCS
scores. To reduce the potential for bias related to inter-
preting the verbal subscale in intubated patients, we ex-
cluded GCS scores confounded by intubation from the
primary analysis. In a separate, secondary analysis, we an-
alyzed scores confounded by intubation by imputing
the verbal subscale score based on the Rutledge model,
Equation 1.
27
GCS combinations and associated level
of consciousness
We identified the 120 possible GCS subscale score com-
binations (4 eye-opening ·5 verbal ·6 motor scores) by
combining each subscale score with every other possible
subscale score. Next, we assigned a diagnosis of coma,
VS/UWS, MCS-, MCS+, PTCS, or recovery from PTCS
(rPTCS) to each behavior of each GCS subscale. We
made these diagnostic determinations a priori based on:
(1) the PTCS case definition,
25
(2) published criteria for
coma,
28,29
VS/UWS, MCS-, and MCS+,
19,20
and (3) the
Coma Recovery Scale-Revised (CRS-R)
30
diagnostic dis-
tinctions between VS/UWS, MCS, and PTCS.
We started by selecting the highest-level behavior
assessed by the GCS, ‘‘oriented’’ (verbal =5), and assign-
ing all GCS combinations with a verbal subscale score of
5 to the rPTCS group. Next, we assigned all GCS scores
with the subsequent highest-level behavior assessed by
the GCS (i.e., ‘‘confused,’’ verbal =4) to the ‘‘PTCS’’
group. We continued along this line of stepwise rea-
soning by identifying the subsequent highest-level
GCS behavior
31
and assigning all GCS combinations
with that behavior the corresponding DoC diagnostic
group (see Fig. 1, Panel B for a flow-diagram illustrating
this procedure).
We calculated the number of times each GCS subscale
score combination was observed in the 39,348 uncon-
founded GCS scores and, separately, the 28,902 GCS
total scores with documented intubation. Because the
first GCS score is often used to determine eligibility for
clinical trials, we repeated this analysis using each sub-
ject’s first GCS score, rather than all available GCS scores.
Finally, we selected four subjects from the TRACK-TBI
dataset to illustrate the challenges that arise when rely-
ing on GCS total scores for clinical management or
research.
Data analysis
For each GCS total score, we calculated: (1) the propor-
tion of GCS subscale score combinations that could result
in each DoC diagnosis; (2) the proportion of all GCS total
scores that are associated with each DoC diagnostic cat-
egory in the TRACK-TBI dataset; and (3) the proportion
of TRACK-TBI subjects whose first valid GCS total
score is associated with each DoC diagnostic category.
Data summaries and descriptive statistics were compiled
in Microsoft Access. TRACK-TBI data collection proto-
cols, case report forms, and data sharing information
can be found on the TRACK-TBI webpage.
26
Results
Participants
Demographic and clinical characteristics are provided in
Table 1. Briefly, mean (standard deviation) age was 41.9
(17.6) years, and 69% were male. Using the traditional
characterization of severity via ED GCS total scores,
13% (n=314) had a severe, 5% (n=119) had a moderate,
and 82% (n=1,975) had a mild TBI. For hospitalized
participants, GCS data were collected for mean (standard
deviation) 2.4 (2.9) days, (median [interquartile range,
IQR] =1.5 [0.3–4.0] days, maximum 62 days). More than
90% of the GCS scores were obtained within the first
seven days post-injury (Supplementary Fig. S2), and
each patient was assessed on average 16.0 (21.8) times
(median [IQR] =8 [2, 21.5] assessments, maximum =263
assessments, Supplementary Fig. S3)
Potential GCS total score combinations
and associated level of consciousness
Each GCS total score is associated with between one
and 18 different combinations of GCS subscale scores.
The 120 GCS combinations and associated DoC diag-
noses are displayed in Supplementary Table S1. Variabil-
ity in DoC diagnoses is highest with GCS total scores of
7–10, each of which can result in a spectrum of DoC di-
agnoses (i.e., VS/UWS, MCS-, MCS+, PTCS, or rPTCS,
[Fig. 2]). The only GCS total scores that invariably iden-
tify patients who are unconscious (coma or VS/UWS)
are 3 and 4, and that invariably identify patients who
have emerged from MCS (PTCS or rPTCS) are 14 and
15. Notably, a GCS total score of 7 or 8 cannot result
in a diagnosis of coma, while a diagnosis of MCS is pos-
sible with any GCS total score in the range of 5–13.
Interestingly, because the only GCS behavior indic-
ative of MCS- is localization (motor =5), the lowest
GCS total score associated with an MCS- diagnosis is
7 (eyes =1, verbal =1, motor =5) while the lowest score
associated with an MCS+diagnosis is 5 (eyes =1,
verbal =3, motor =1).
Analysis of GCS data in the TRACK-TBI study
The frequency with which each of the 120 GCS subscale
score combinations occurs in the TRACK-TBI data-
set is provided in Supplementary Table 1. Not all GCS
combinations and total scores are represented equally
in this TRACK-TBI sample. Higher-level GCS behav-
iors are more prevalent, reflecting the characteristics of
the TRACK-TBI dataset and the separate analysis of scores
confounded by intubation (Supplementary Fig. S4).
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Approximately 25% of the 120 GCS combinations were
never observed across the entire TRACK-TBI dataset
(Supplementary Table S2).
In the TRACK-TBI dataset, the only GCS total scores
that were always associated with coma or VS/UWS were
3, 4, 5, and 6, and the only total scores that were always
associated with recovery from MCS (i.e., PTCS, rPTCS)
were 14 and 15. The variability of DoC diagnoses was
highest for GCS scores of 7–12 (Fig. 3). For example, a
GCS total score of 8, which, by convention, indicates a
severe injury and is sometimes used to define coma,
was observed 654 times and was associated with coma
AB
FIG. 1. Decision tree associating individual Glasgow Coma Scale (GCS) subscale behaviors with disorder of
consciousness (DoC) diagnoses. (A) The GCS subscales and behaviors, as described on the official GCS
website.
31
(B) The flow diagram illustrates our approach to assigning a DoC diagnosis to GCS behaviors. We
started by selecting the highest-level behavior on the GCS, ‘‘oriented’’ (verbal=5), and assigning all GCS
combinations with a verbal subscale score of 5 to a recovered from post-traumatic confusional state (rPTCS)
diagnostic group. Next, we assigned all GCS scores with the subsequent highest-level behavior on the GCS
(i.e., ‘‘confused,’’ verbal =4) a diagnosis of PTCS. We continued along this stepwise line of reasoning by
identifying the subsequent highest-level GCS behavior and assigning the corresponding DoC diagnosis to
all GCS combinations with that behavior, until the only behaviors remaining were flexion and extension on
the motor scale, reflective of coma. Because the GCS does not include all behaviors associated with DoC
diagnoses, this decision tree is not meant to provide a clinical diagnosis. For example, patients with GCS
behaviors consistent with vegetative state/unresponsive wakefulness syndrome (VS/UWS) were not
assessed for minimally conscious state (MCS) behaviors such as visual pursuit and automatic motor
responses, which would have indicated a MCS. The color-coding in the DoC diagnostic categories in
(B) aligns with the color-coding of the behaviors in (A). For example, a GCS-based diagnosis of recovered
from posttraumatic confusional state (rPTCS) (shaded green in [B]) is obtained by demonstrating orientation
(GCS verbal =5, shaded green in [A]). rPTCS, recovered from PTCS (best GCS subscale score is GCS
verbal =5); PTCS, post-traumatic confusional state (best GCS subscale score is GCS verbal =4); MCS+,
minimally conscious state with evidence of language function (best GCS subscale score is GCS verbal =3or
GCS motor =6); MCS-, MCS without evidence of language function GCS (best GCS subscale score is GCS
motor =5); VS/UWS, vegetative state/unresponsive wakefulness syndrome (best GCS subscale score is GCS
eye opening >1 or verbal =2). Color image is available online.
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in 0%; VS/UWS in 5%; MCS- in 78%; and MCS+in 17%
of scores. Conversely, different total scores were associ-
ated with the same DoC diagnoses. For example, a diag-
nosis of MCS- was associated with between 83% and
19% of GCS total scores of 7, 8, 9, 10, and 11.
Results were similar when evaluating only the first
valid GCS score across TRACK-TBI subjects (Supple-
mentary Fig. S5). Results of the secondary analysis im-
puting the GCS verbal score for intubated patients are
in the Supplementary Materials text and Supplementary
Table S3.
Case studies
We present four scenarios to illustrate how use of GCS
total scores may result in misleading interpretation of
level of consciousness (Fig. 4). For Participants 1 and 2,
GCS subscale behavioral profiles result in a total score
of 8 and an injury categorization of ‘‘severe.’’ For Partic-
ipant 1, however, the profile is consistent with VS/UWS,
while for Participant 2 the profile is consistent with
MCS+. For Participants 3 and 4, the GCS total score
differs by three points—total score =7 versus 10—
corresponding to severe and moderate injury, respec-
tively. Nevertheless, the behavioral profiles both reflect
the same level of consciousness (i.e., MCS-).
Discussion
In this study of 2455 participants with acute TBI, we found
substantial heterogeneity in the level of consciousness as-
sociated with GCS total scores. While identical total scores
reflected different levels of consciousness, different total
scores reflected the same level of consciousness. Lower
GCS total scores did not always indicate a more severe in-
jury, and vice versa. Importantly, although a GCS total
score of 8 is often used as the threshold to operationally
define ‘‘coma’’ in clinical trials, no patients with GCS
total scores of 7 or 8 had a diagnosis of coma. Given
the prognostic relevance of precise assessment of level
of consciousness
22,32
and the importance of consistent
subject stratification in clinical trials,
6
the GCS total
score may, therefore, be a suboptimal tool for defining
TBI severity or monitoring recovery. Our results support
previous studies suggesting that the behavioral subscale
profile underlying the total GCS score may be more clin-
ically meaningful than the total score itself
7,11,14,15
and
shed new light on the limitations of the GCS total score
as a clinical and investigational tool.
In this study, we showed that the GCS total score does
not differentiate DoC diagnoses.
19
The GCS subscales,
however, are also limited because they omit behaviors,
such as visual pursuit,
23
that are necessary to distin-
guish between VS/UWS, MCS-, and MCS+. Failing to
assess these behaviors could contribute to misdiagnosis,
inaccurate prognosis, and heterogeneous clinical trial sam-
ples. GCS items also lack a standardized approach for
subscale administration and a consistent way of docu-
menting factors such as sedation and intoxication that
influence performance.
3
Guidance on how to assess be-
haviors such as command-following and what criteria
must be met to document a localizing response are needed
to ensure that changes in scores reflect the patient’s true
responsiveness rather than the examiner’s approach to-
ward administration of the measure. Recognizing these
limitations of the GCS, the original authors have pro-
vided additional recommendations to aid in proper use of
the subscale and total GCS scores.
31
When one or more GCS subscales are confounded, the
opportunity to detect conscious awareness is further re-
duced. In such cases, it is especially important to review
individual behaviors rather than total scores and to con-
duct further comprehensive assessments aimed at differ-
entiating VS/UWS from MCS.
Table 1. Patient Demographics and Injury Characterization
All subjects
All subjects included
in analysis
a
N=2552 N=2455
Age
Mean (SD) 41.9 (17.6) 41.9 (17.6)
Sex
Male 1767 (69%) 1699 (69%)
Female 785 (31%) 756 (31%)
Race
White 1955 (78%) 1878 (78%)
Black 406 (16%) 395 (16%)
Asian 94 (4%) 91 (4%)
Native Hawaiian/Pacific
Islander
7 (0%) 7 (0%)
Alaska native/Inuit 2 (0%) 2 (0%)
Indian 7 (0%) 7 (0%)
Mixed race 40 (2%) 40 (2%)
Unknown 41 35
Hispanic
No 1996 (79%) 1917 (79%)
Yes 517 (21%) 505 (21%)
Unknown 39 33
Education years
Mean (SD) 13.3 (2.9) 13.3 (2.9)
Unknown 175 162
Injury cause
Road traffic 1456 (57%) 1395 (57%)
Fall 680 (27%) 660 (27%)
Other accident 133 (5%) 129 (5%)
Violence 169 (7%) 163 (7%)
Other 99 (4%) 94 (4%)
Unknown 15 14
ED GCS severity
Mean (SD) 13.0 (3.8) 13.2 (3.6)
Severe (3-8) 361 (15%) 314 (13%)
Moderate (9-12) 123 (5%) 119 (5%)
Mild (13-15) 2000 (81%) 1975 (82%)
Unknown 68 47
Highest level of care
ED 531 (21%) 508 (21%)
Ward 875 (34%) 870 (35%)
ICU 1146 (45%) 1077 (44%)
SD, standard deviation; ED, emergency department; GCS, Glasgow
Coma Scale; IC, intensive care unit.
a
Subjects with at least one valid GCS score.
DIAGNOSING CONSCIOUSNESS WITH THE GCS 3299
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Approaches aimed at providing a score for confounded
subscales, such as applying imputation algorithms or
assigning the lowest possible value of ‘‘1’’, may lead
to misclassification of level of consciousness. In fact,
we found that imputing verbal subscale scores drastically
and artificially reduced the opportunity to observe the
various DoC diagnoses associated with each GCS total
score. Although there are alternate approaches to imput-
ing confounded GCS verbal scores, none address the
issue of reduced variability, and there are no reliable
approaches for imputing confounded eye and motor
subscale scores. Therefore, when one or more GCS sub-
scales are confounded, an accurate total score cannot be
calculated. The Full Outline of UnResponsiveness
(FOUR) score is designed to overcome some of the
limitations of the GCS. The FOUR score, however, also
omits behaviors associated with MCS, has not been
validated in TBI, and lacks strong psychometrical
properties.
9,33
Of the 120 combinations of the GCS total score, about
25% were not observed a single time across our sample of
39,348 GCS scores. This finding suggests that some GCS
FIG. 2. Frequency of disorder of consciousness (DoC) diagnoses by Glasgow Coma Scale (GCS) total score.
The GCS comprises three subscales: eye opening, motor, and verbal responses. There are 120 possible
combinations of subscale scores, each of which can be associated with a DoC diagnosis. All scores other
than 3 and 15 are associated with multiple DoC diagnoses. Scores of 7–11 have the largest number of
potential subscale combinations. The ‘‘N’’ below each GCS total score indicates the number of possible GCS
subscale score combinations for each GCS total score. For example, there are 18 different ways a GCS total
score of 9 could be achieved. rPTCS, recovered from PTCS (best GCS subscale score is GCS verbal =5); PTCS,
post-traumatic confusional state (best GCS subscale score is GCS verbal =4); MCS+, minimally conscious
state with evidence of language function (best GCS subscale score is GCS verbal =3 or GCS motor =6);
MCS-, MCS without evidence of language function GCS (best GCS subscale score is GCS motor =5); VS/UWS,
vegetative state/unresponsive wakefulness syndrome (best GCS subscale score is GCS eye opening >1or
verbal =2). Color image is available online.
3300 BODIEN ET AL.
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subscale combinations are clinically unlikely to co-occur.
Observation of these infrequent combinations clinically
and in research may signal errors in administration or
scoring or a failure to identify confounding factors.
Our mapping of GCS behaviors onto levels of con-
sciousness was conducted objectively based on published
diagnostic criteria. Because the GCS does not test all be-
haviors associated with each DoC diagnosis, however,
the DoC diagnoses we associated with GCS behaviors
are approximations and not intended for clinical diagnos-
tic purposes. Further, because our study relies on a con-
ceptual mapping of GCS behaviors onto DoC diagnoses
and our sample is heavily weighted toward mild TBI,
follow-up studies that prospectively evaluate level of
consciousness using a comprehensive standardized bed-
side assessment in a large cohort of participants with se-
vere TBI will be needed to confirm our findings.
Interestingly, the GCS motor subscale has been shown
to be more sensitive for classifying injury severity
34,35
and predicting survival,
11
compared with the GCS total
score, although this may not be the case for older pa-
tients.
36
Given that the GCS eye-opening subscale does
FIG. 3. Frequency of disorder of consciousness (DoC) diagnoses by Glasgow Coma Scale (GCS) total score
in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) database. We
assigned a DoC diagnosis to 39,348 GCS scores from 2455 patients in the TRACK-TBI database based on the
Decision Tree algorithm in Figure 1. Each color represents a different DoC diagnosis. Total scores ranging
from 7–11 had the highest variability, such that a single GCS score could indicate multiple different DoC
diagnoses, while different GCS total scores could indicate the same DoC diagnosis. The ‘‘N’’ below each GCS
total score indicates the number of times each GCS total score occurs in the TRACK-TBI database. rPTCS,
recovered from PTCS (best GCS subscale score is GCS verbal =5); PTCS, post-traumatic confusional state (best
GCS subscale score is GCS verbal =4); MCS+, minimally conscious state with evidence of language function
(best GCS subscale score is GCS verbal =3 or GCS motor =6); MCS-, MCS without evidence of language
function GCS (best GCS subscale score is GCS motor =5); VS/UWS, vegetative state/unresponsive wakefulness
syndrome (best GCS subscale score is GCS eye opening >1 or verbal =2). Color image is available online.
DIAGNOSING CONSCIOUSNESS WITH THE GCS 3301
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not include any behaviors differentiating VS from MCS
and that the verbal subscale is often confounded by intu-
bation, GCS motor subscale may also be the most likely
to accurately characterize 6- and 12-month outcome.
Finally, the utility of GCS scores for assessing con-
sciousness may vary based on patient acuity and setting.
For patients with GCS £8, regardless of the subscale
composition of this score (e.g., E3, V2, M3 verses E2,
V1T, M5), current guidelines from the Brain Trauma
Foundation recommend neurosurgical intervention to
place an intracranial pressure monitoring device.
37
Whether outcome is affected by the GCS subscale com-
position of the total score that leads to the neurosurgical
intervention is unknown. Our findings, however, suggest
FIG. 4. Case illustrations of the variable association between Glasgow Coma Scale (GCS) total scores and
disorder of consciousness (DoC) diagnoses. For Participants 1 and 2, GCS subscale score behavioral profiles
result in a total score of 8 and a severe injury categorization. For Participant 1, however, the profile is
consistent with a DoC diagnosis of vegetative state/unresponsive wakefulness syndrome (VS/UWS), while for
Participant 2, the profile is consistent with minimally conscious state with evidence of language function
(MCS+). Characterizing both patients as having a ‘‘severe’’ injury ignores the highly variable approach toward
clinical management applied to patients who are unconscious versus those who are conscious and following
commands.
17
With regard to research, both Participants 1 and 2 would be allocated to the same study arm
based on the total GCS score, despite having markedly different levels of consciousness. This would result in a
heterogenous group and make it more difficult to determine differences in treatment efficacy or outcome.
For participants 3 and 4 the GCS total scores differ by 3 points, and the total scores are consistent with severe
versus moderate injury, respectively. Nevertheless, the behavioral profiles both reflect an MCS without
evidence of language function (MCS-) level of consciousness. In this case, ascribing different injury severity
categories based on the total score would create an erroneous distinction between Participants 3 and 4 who
are, in fact, functioning at the same level. In a research study, these two patients may be placed in separate
severity groups, or one participant may be excluded, creating an artificial distinction based on GCS total
scores that is not supported by the actual level of consciousness. Consequently, this may obscure the effect of
treatment, reflecting instead heterogeneity across study groups. VS/UWS, vegetative state/unresponsive
wakefulness syndrome (best GCS subscale score is GCS eye opening >1 or verbal =2); MCS+,minimally
conscious state with evidence of language function (best GCS subscale score is GCS verbal =3orGCS
motor =6); MCS-, MCS without evidence of language function GCS (best GCS subscale score is GCS motor =5).
Color image is available online.
3302 BODIEN ET AL.
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that knowledge of the subscale scores may be important
even in the setting of rapid triage for clinical procedures,
to the extent that these decisions are informed by a pa-
tient’s level of consciousness.
Although more than 90% of GCS scores in this study
were obtained within the first seven days post-injury, ap-
proximately 0.5% of GCS scores were obtained in what is
considered prolonged DoC (more than 28 days post-
injury).
32
The generalizability of our findings to patients
with prolonged DoC requires further investigation.
In the 45 years since its development, the GCS has
continued to have a uniquely prominent role in assess-
ment of TBI. The overwhelming adoption of the GCS
is likely related to its historical positioning as one of
the first scales to quantify brain injury severity and create
a common language around recovery from TBI-related
coma.
2
The GCS is also simple and fast to administer
and is routinely identified as a statistically significant, if
modest, indicator of outcome at the group level.
2,4,10,38
Despite the development of various revisions,
4
how-
ever, the prognostic validity of the GCS, even at the
subscale level, is insufficient for predicting outcome in
individual patients. Nevertheless, early behavioral as-
sessment of TBI, grounded in the GCS, continues to in-
form individual prognostic discussions that may lead to
withdrawal of life-sustaining therapy. More refined meth-
ods for quantifying impairments in consciousness that
maximize reliability, mitigate misdiagnosis, and hence
reduce prognostic errors, are clearly needed.
A standardized measure of level of consciousness
with strong psychometric properties that assesses the
full range of behaviors underlying DoC diagnosis should
complement the GCS evaluation. The CRS-R,
30
a TBI
Common Data Element
5
that is recommended by the
American Academy of Neurology and the American
Congress for Rehabilitation Medicine
31
practice guide-
lines, meets these criteria. The CRS-R, however, is not
validated in the ICU setting and is lengthy, making it
difficult to administer in patients with acute TBI who
are sedated, rapidly fluctuating, or clinically unstable. An
abbreviated version of the CRS-R, the CRS-R FAST
(CRS-R For Accelerated Standardized Testing) is cur-
rently being investigated (NCT #03549572). The FOUR
score is designed for use in the ICU and can be adminis-
tered in a few minutes, but has limitations for diagnosing
DoC, as described above.
Conclusion
Before assigning an injury severity classification based
on GCS total scores, clinicians and investigators should,
at a minimum, consider the information provided by the
GCS behavioral profile and potential confounding fac-
tors. Subscale score analysis is especially important for
GCS total scores of £8 because of the risk of incorrectly
establishing a diagnosis of coma. Designing electronic
medical record systems to prompt for GCS subscale
scores and potential confounds may aid in ensuring rou-
tine documentation of this information. Accurate clinical
assessment and successful clinical trials will ultimately
necessitate comprehensive behavioral measures that rig-
orously and reliably classify patients according to their
level of consciousness, cognition, and function.
TRACK-TBI Investigators
Neeraj Badjatia, University of Maryland, College Park,
MD; Ann-Christine Duhaime, MassGeneral Hospital
for Children, Boston, MA; Adam R. Ferguson, University
of California, San Francisco, San Francisco, CA; Etienne
Gaudette, PhD, University of Toronto, Toronto, Ontario,
Canada; Shankar Gopinath, Baylor College of Medicine,
Houston, TX; C. Dirk Keene, University of Washing-
ton, Seattle, WA; Michael McCrea, Medical College
of Wisconsin, Wauwatosa, WI; Randall Merchant, Vir-
ginia Commonwealth University, Richmond, VA; Pratik
Mukherjee, University of California, San Francisco, San
Francisco, CA; Laura B. Ngwenya, University of Cin-
cinnati, Cincinnati, OH; David Okonkwo, University
of Pittsburgh, Pittsburgh, PA; Ava Puccio, University
of Pittsburgh, Pittsburgh, PA; Gabriella Sugar, University
of California, San Francisco, San Francisco, CA; David
Schnyer, University of Texas, Austin, Austin, TX; John
K. Yue, University of California, San Francisco, San
Francisco, CA; Ross Zafonte, Harvard Medical School,
Boston, MA.
Authors’ Contributions
Yelena G. Bodien: study concept, design and oversight,
acquisition, analysis, and interpretation of data, drafting/
revising the manuscript, critical revision of the manu-
script for intellectual content; Alice Barra: study concept,
interpretation of data, drafting/revising the manuscript,
critical revision of the manuscript for intellectual con-
tent; Nancy R. Temkin: study concept, analysis and in-
terpretation of data, drafting/revising the manuscript,
critical revision of the manuscript for intellectual con-
tent; Jason Barber: analysis and interpretation of data,
drafting/revising the manuscript, critical revision of the
manuscript for intellectual content; Brandon Foreman:
study concept, design and interpretation of data, drafting/
revising the manuscript, critical revision of the manuscript
for intellectual content; Mary Vassar: study concept, de-
sign and interpretation of data, drafting/revising the man-
uscript, critical revision of the manuscript for intellectual
content; Claudia Robertson: study concept, design and
interpretation of data, drafting/revising the manuscript,
critical revision of the manuscript for intellectual content;
Sabrina R. Taylor: study concept, design and interpreta-
tion of data, drafting/revising the manuscript, critical re-
vision of the manuscript for intellectual content; Amy J.
DIAGNOSING CONSCIOUSNESS WITH THE GCS 3303
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Markowitz: study concept, drafting/revising the manu-
script, critical revision of the manuscript for intellectual
content Geoffrey T. Manley, Joseph T. Giacino, and
Brian L. Edlow: study concept, design and oversight, ac-
quisition, analysis, and interpretation of data, drafting/
revising the manuscript, critical revision of the manu-
script for intellectual content. Neeraj Badjatia, Pratik
Mukherjee, David Okonkwo, Ava Puccio: study metrics
development/validation, data collection, data quality/
curation; Ann-Christine Duhaime: study metrics
development/validation, data collection, data quality/
curation, critical revision of the manuscript for intellec-
tual content; Adam R. Ferguson: data analysis and bio-
statistical support; Etienne Gaudette: study metrics
development/validation; Shankar Gopinath: data col-
lection; C. Dirk Keene: data collection, data quality/
curation, critical revision of the manuscript for intellec-
tual content; Michael McCrea: study metrics development/
validation; Randall Merchant: collection, data quality/
curation: Laura B. Ngwenya: data collection, data quality/
curation; Gabriella Sugar, David Schnyer, John K. Yue:
data collection, data quality/curation; Ross Zafonte:
study metrics development/validation
Funding Information
This study was supported by the NIH National Institute
of Neurological Disorders and Stroke (R21NS109627,
RF1NS115268, UH3NS095554, U01 NS1365885, U01-
NS086090), NIH Director’s Office (DP2 HD101400),
National Institute on Disability, Independent Living and
Rehabilitation Research (NIDILRR), Administration for
Community Living (90DPCP0008-01-00, 90DP0039),
James S. McDonnell Foundation, and Tiny Blue Dot
Foundation, U.S. Department of Defense (W81XWH-
14-2-0176, X81XWH-18-DMRDP-PTCRA), National
Science Foundation (1014552)
Author Disclosure Statement
Y.G. Bodien reports funding from: NIH National Institute
of Neurological Disorders and Stroke ( U01 NS1365885,
U01-NS086090), National Institute on Disability, Inde-
pendent Living and Rehabilitation Research (NIDILRR),
Administration for Community Living (90DPCP0008-
01-00, 90DP0039), James S. McDonnell Foundation,
and Tiny Blue Dot Foundation; A. Barra reports funding
from: National Institute on Disability, Independent Liv-
ing and Rehabilitation Research (NIDILRR), Adminis-
tration for Community Living (90DPCP0008- 01-00,
90DP0039); N. R. Temkin reports funding from: NIH
National Institute of Neurological Disorders and Stroke
( U01 NS1365885, U01-NS086090), US Department of
Defense (W81XWH-14-2-0176); J. Barber reports fund-
ing from: NIH National Institute of Neurological Disor-
ders and Stroke (U01-NS086090), US Department of
Defense (W81XWH-14-2-0176); B. Foreman reports
funding from: NIH National Institute of Neurological
Disorders and Stroke (U01-NS086090), US Department
of Defense (X81XWH-18-DMRDP-PTCRA), National
Science Foundation (1014552); M. Vassar reports fund-
ing from: NIH National Institute of Neurological Disor-
ders and Stroke (U01- NS086090), US Department of
Defense (W81XWH-14-2-0176); C. Robertson reports
funding from: NIH National Institute of Neurological
Disorders and Stroke (U01-NS086090); S. R. Taylor
reports funding from: NIH National Institute of Neuro-
logical Disorders and Stroke (U01-NS086090); A.J. Mar-
kowitz reports funding from: NIH National Institute of
Neurological Disorders and Stroke (U01-NS086090);
G.T. Manley reports funding from: NIH National Ins-
titute of Neurological Disorders and Stroke (U01-
NS086090); J. T. Giacino reports funding from: NIH
National Institute of Neurological Disorders and Stroke
(U01-NS086090, UH3NS095554), US Department of
Defense (W81XWH-14-2-0176), National Institute on
Disability, Independent Living and Rehabilitation Research
(NIDILRR), Administration for Community Living
(90DPCP0008-01-00, 90DP0039); B. L. Edlow reports
funding from: NIH National Institute of Neurological
Disorders and Stroke (R21NS109627, RF1NS115268),
NIH Directors Office (DP2 HD101400), James S.
McDonnell Foundation, and Tiny Blue Dot Foundation.
Supplementary Material
Supplementary Text
Supplementary Table S1
Supplementary Table S2
Supplementary Table S3
Supplementary Figure S1
Supplementary Figure S2
Supplementary Figure S3
Supplementary Figure S4
Supplementary Figure S5
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