Chapter 1

Behavioral Assessment and Diagnosis

of Disorders of Consciousness

Caroline Schnakers and Steve Majerus

Abstract Behavioral assessment is a critical step for the detection of signs of con-
sciousness and, hence, for diagnosis of states of altered consciousness. However,
because of the presence of compromising factors such as severe functional and cog-
nitive impairment, accurate diagnosis is a challenging enterprise, leading to serious
consequences on the patient’s ongoing care but also on the patient’s end of care. In
this review, we will describe the behavioral characteristics of the main clinical enti-
ties through which severely brain-injured patients transit before fully recovering
from coma, we will describe methods for assessing consciousness at the bedside,
and we will discuss the existing tools that help clinicians formulating an accurate
diagnosis.

Introduction

During these last years, there has been increasing fascination for the field of disor-
ders of consciousness. Due to progress in intensive care, more and more severely
brain-injured patients survive their initial brain insult, but many of these will go
through various states of impaired consciousness. The prevalence of these patients
is estimated at 46 per million in the United States, 14 per million in Great Britain [1],
and 36 per million in Belgium [2]. Many patients will remain in a vegetative state for
a more or less extended period of time before regaining some level of consciousness
(minimally conscious state). Some of these cases have received important coverage

C. Schnakers, Ph.D. (*)

Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA
Department of Research, Casa Colina Hospital and Centers for Healthcare,
Pomona, CA, USA
e-mail: [email protected]; [email protected]
S. Majerus, Ph.D.
Department of Psychology, Cognition and Behavior, University of Liège,
Boulevard du Rectorat 3 B33, 4000 Liège, Belgium
e-mail: [email protected]

© Springer International Publishing AG 2018 1

C. Schnakers, S. Laureys (eds.), Coma and Disorders of Consciousness,
DOI 10.1007/978-3-319-55964-3_1
2 C. Schnakers and S. Majerus

by the media, such as the case of Terri Schiavo (1963–2005) who stayed in a vegeta-
tive state for 15 years after a cardiac arrest or the case of Terry Wallis who emerged
from a minimally conscious state 19 years (1984–2003) after a severe traumatic
brain injury [3]. At the same time, prolonged hospitalization is expensive. In the
United States, the costs are estimated at 600,000–1,875,000 dollars per year per
patient with severe traumatic injury [4]. Questions regarding end-­of-­life decisions
are critical here, particularly in chronic vegetative patients. In a recent European
survey (n = 2475), the majority of medical and paramedical professionals (66%)
agreed to withdraw life support for chronic vegetative patients, while only 28%
agreed for patients in a chronic minimally conscious state. Many clinicians reported
that they would not want to be life-supported if they happened themselves to be in a
chronic vegetative state (82%) or if they were in a chronic minimally conscious state
(67%) [5]. The social, economic, and ethical consequences associated with disor-
ders of consciousness, and particularly the vegetative state, are huge.
The term vegetative indicates preserved physiological functions (cardiac, respi-
ratory, sleep/wake cycles) without clear signs of consciousness of either the self or
the environment. In a sense, the body works without the mind. One of the few ways
we have to differentiate patients in a vegetative state from conscious patients is to
observe their spontaneous behaviors and their reactions to stimuli occurring in their
environment. This behavioral assessment requests thorough expertise on behalf of
the clinician. It also depends on the physical and mental capacities (particularly, the
vigilance level) of the patient at the time of assessment. Missing signs of conscious-
ness is not a rare fact, and diagnostic errors are frequent (i.e., around 40%) [6–8].
The diagnosis is, however, crucial. It influences the way the patient’s care will be
oriented and the way end-of-life decisions will be considered with the patient’s fam-
ily. Developing valid and sensitive behavioral scales to detect the presence of signs
of consciousness, even subtle, therefore, represents a real challenge.

Disorders of Consciousness

Coma

Patients who survive a severe brain injury can remain unconscious for several
weeks, being neither awake nor conscious. They are in a state called coma, defined
as “a pathological state marked by severe and prolonged dysfunction of vigilance
and consciousness” [9] (Fig. 1.1 and Table 1.1). This state usually results either
from a lesion limited to the brainstem (involving the reticular activating system) or
from a global brain dysfunction (most often caused by diffuse axonal injury after
traumatic brain injury). The distinguishing features of coma are the continuous
absence of eye opening (spontaneously or after stimulation) and the absence of
oriented or voluntary motor or verbal (including vocalization) responses. There is
no evidence of visual fixation or pursuit, even after manual eye opening. This state
must last at least 1 h to be differentiated from a transient state such as syncope, acute
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 3

Conscious

Non-Conscious

Behaviorally indistinguishable Conscious

patients wake
Behavioral
Drowsiness

Light
sleep MCS
Ability to produce
motor behavior
Deep
sleep

General
Non-behavioral
Anesthesia
Coma Aware
Content of
VS consciousness
(awareness)
Non-awake Non-aware

Level of
Awake
consciousness
(wakefulness)

Fig. 1.1 The conundrum of consciousness. Disorders of consciousness are defined by two main
components: the level of consciousness and the content of consciousness. This figure illustrates
where different states (i.e., coma; vegetative state, VS; minimally conscious state, MCS, but also
states related to sleep and anesthesia) are placed on both continuum. It also represents where
patients with covert cognition would be placed (adapted from Monti et al., 2012)

confusion, or delirium. Prolonged coma is rare as this condition usually resolves

within 2–4 weeks, most often evolving into a vegetative state or a minimally con-
scious state [10].
The prognosis is influenced by factors such as etiology (patients with traumatic
brain injury have a better outcome than patients suffering from a cerebrovascular
accident), general medical condition, and age. A negative outcome is expected if,
after 3 days of observation, there are no pupillary or corneal reflexes, only stereo-
typed or absent motor responses to noxious stimulation, and an isoelectric electro-
encephalogram (EEG). A bilateral absence in parietal regions of the N20 evoked
potential to somatosensory stimuli is also a strong predictor of death in comatose
patients [11].
Being in a coma is different from being brain dead. In patients with brain death,
critical functions such as respiration and circulation, neuroendocrine and homeo-
static regulation, and consciousness are absent. The patient is apneic and unreactive
to environmental stimulation. The term brain death requires a bedside demonstra-
tion of irreversible cessation of all functions of the brain, including brainstem func-
tions. After controlling for a possible impact of pharmacological treatment, toxins,
and hypothermia, the diagnosis of brain death can be made within 6–24 h, usually
using a thorough assessment of brainstem reflexes, an apnea test (to demonstrate the
absence of a breathing drive), and a cerebral angiography, an X-ray scan, or tran-
scranial Doppler imaging (to demonstrate the absence of brain functions) [12].
4 C. Schnakers and S. Majerus

Table 1.1 Comparison of the behavioral features of coma, VS, MCS−, MCS+, emergence from
MCS (EMCS), and LIS
Coma VS MCS− MCS+ EMCS LIS (classic)
Eye opening None Spontaneous Spontaneous Spontaneous Spontaneous Spontaneous
Movement None Reflexive/ Automatic/ Automatic/ Functional Reflexive/
patterned object object object use patterned
manipulation manipulation
Response to Posturing/ Flexion Localization Localization N/A Flexion
pain none withdrawal/ withdrawal/
posturing posturing
Visual response None Startle Object Object Object Object
localization/ recognition recognition recognition
pursuit/
fixation
Affective None Random Contingent Contingent Contingent Random
response (presence of
pathological
laughs/tears)
Response to None None None Reproducible Consistent/ Consistent
command reproducible (using
eye-related
commands)
Verbalization None None Random Intelligible Intelligible None
vocalization/ words words
none
Communication None None Unreliable Unreliable Reliable Reliable (using
alphabetical
board)

Vegetative State

In 1972, the term vegetative state (VS) was first introduced by Jennet and Plum to
describe “an organic body capable of growth and development but devoid of sensa-
tion and thought” [13] (Fig. 1.1 and Table 1.1). This new clinical entity was identi-
fied following the implementation of artificial breathing techniques in intensive care
units. Since then, the number of scientific studies performed on VS patients has
continuously increased. More precisely, less than ten articles were published from
1975 to 1985, compared with more than five hundreds of articles from 2010 to 2015
(Fig. 1.2).
Behaviorally, patients in VS open their eyes spontaneously or in response to
stimulation and present preserved autonomic functions (e.g., breathing, cardiovas-
cular regulation, thermoregulation), but they are not conscious and show only
reflexive behaviors [10]. The VS often results from an injury involving the white
matter or bilateral lesions of the thalamus (i.e., intralaminar nuclei) [14, 15]. How
can doctors explain to the family such a state? These patients breathe normally and
have their eyes open. They even have prolonged periods with eyes closed, leading
to the impression that the patient is sleeping. We now know that this impression may
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 5

536

284

109
66
50
28
7 8

1975/1980 1980/1985 1985/1990 1990/1995 1995/2000 2000/2005 2005/2010 2010/2015

Fig. 1.2 Annual number of publications on vegetative state between 1975 and 2015. Results of a
PubMed search using the terms vegetative state, consciousness, and awareness

be wrong. When the eyes are closed, no specific electroencephalographic changes

are noticed, and EEG characteristics of the different sleep stages (e.g., slow wave
sleep, rapid eye movement) are often absent [16]. The patients may also moan and
show smiling, crying, or grimacing, but these behaviors are inappropriate and
appear out of context. Even randomly produced single words have been reported in
patients diagnosed with VS [17]. All of these features will puzzle the patient’s fam-
ily and complicate the work of the medical staff, who may be inclined to experience
burnout (i.e., a recent study showed that one out of five healthcare workers caring
for patients in a disorder of consciousness are in burnout, while 33% present an
emotional exhaustion) [18]. Accurate information and psychological assistance are
essential for helping the family (and also the medical staff) to cope with this dra-
matic situation [19].
The VS state may last for days, months, or even years. After 1 year, for traumatic
etiologies, or 3 months, for non-traumatic etiologies, the VS can be considered as
permanent. In such cases, the patient’s chance of recovery is less than 5%. Only
after that point can the ethical and legal issues concerning withdrawal of treatment
be discussed [20]. Given the negative connotation of the term “vegetative state,” the
European Task Force on Disorders of Consciousness has proposed the use of a more
neutral and descriptive term, such as “unresponsive wakefulness syndrome” [21].
During end-of-life decision-making, the presence of any sign of consciousness must
be investigated and excluded using behavioral and neuroscientific approaches (such
as neuroimaging and electrophysiology). The challenges that clinicians face when
differentiating unconscious from conscious states are illustrated by cases that
received lots of attention by the media such as Tony Bland in the United Kingdom
6 C. Schnakers and S. Majerus

(1993), Terri Schiavo in the United States (2005), and Eluana Englaro in Italy
(2009) [22–24]. Thorough examinations had been conducted for each of these
patients; the extreme decision of end of life was considered. The distinction between
conscious and unconscious states is very difficult to make given that patients can
present subtle behavioral signs which can easily be missed and which differentiate
the vegetative state from the minimally conscious state.

Minimally Conscious State

The minimally conscious state (MCS) was identified more recently than the VS
and the coma. It was defined in 2002 by the Aspen Workgroup as being character-
ized by the presence of inconsistent but clearly discernible behavioral signs of
consciousness (Fig. 1.1 and Table 1.1) [25]. Patients evolving from a VS to an
MCS are still awake but begin to show oriented behaviors such as visual pursuit.
The earlier this behavior appears, the better the outcome will be. The presence of
oriented eye movements is therefore crucial, but it is also one of the most difficult
signs of consciousness to detect and requires the use of sensitive diagnostic tools
[8, 26, 27]. More globally, signs of consciousness in MCS patients may be hard to
observe because they are inconsistent in time, due to high vigilance fluctuations.
They must be replicated within a given examination to meet the diagnostic criteria
for MCS. It is generally necessary to conduct serial examinations before an accu-
rate diagnosis can be made. Complicating further the diagnosis is the fact that
patients may fluctuate between VS and MCS before the level of consciousness
stabilizes [28].
MCS is diagnosed when there is clear evidence of one or more of the following
behaviors: simple command-following (e.g., “shake my hand”), gestural or verbal
yes/no responses (regardless of accuracy), intelligible verbalization, and move-
ments or affective behaviors that occur in contingent relation to relevant environ-
mental stimuli and are not attributable to reflexive activity. Examples of contingent
motor and affective responses include (1) episodes of crying, smiling, or laughter
produced by the linguistic or visual content of emotional but not neutral stimuli, (2)
vocalizations or gestures that occur in direct response to verbal prompts, (3) reach-
ing for objects with a clear relationship between object location and direction of
reach, (4) touching or holding objects in a manner that accommodates the size and
shape of the object, and (5) visual pursuit or sustained fixation in response to mov-
ing or salient stimuli. As different functional neuroanatomical features have been
observed, the MCS has recently been subdivided in two clinical entities, MCS+ and
MCS−, based on the presence or absence of receptive and expressive language (i.e.,
response to command and intelligible verbalization) [29]. The specific behaviors
required to fulfill the criteria for MCS+ and MCS− remain a matter of debate and
require further empirical investigation before they can be incorporated into clinical
practice.
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 7

Emergence from MCS is defined by the reemergence of reliable and consistent

interactive communication (which may occur through speech, writing, yes/no sig-
nals, or augmentative communication devices) or a functional object use (i.e., dis-
crimination and appropriate use of two or more objects) [25].
Patients in MCS may progress quickly or slowly, whereas others remain in this
condition permanently. Formal prognostic guidelines do not exist for MCS. However,
patients in MCS improve faster and have better prospects for functional recovery
than those in VS, and outcomes are generally more favorable for those with trau-
matic versus non-traumatic injuries [30–32]. The original report describing this
condition states that most of those who remain in MCS for 12 months will remain
permanently severely disabled [33]. However, recent studies suggest that signs of
recovery after severe brain injury may be observable over longer time periods and
approximately one in five MCS patients will eventually continue his life at home or
in the community. The duration of MCS nevertheless seems to be a strong predictor
of the length of confusional state/posttraumatic amnesia [30]. The early recovery
(within 8 weeks) of target conscious behaviors such as visual pursuit and response
to command have been linked to good functional outcome several years after the
injury [27, 31].

 on’t Judge a Book by Its Cover: The Difficult Diagnoses

D
of Locked-In Syndrome and Covert Cognition

Locked-In Syndrome

The locked-in syndrome (LIS) is marked by tetraplegia and anarthria in the con-
text of preserved consciousness and a near-normal to normal cognitive function-
ing [34, 35] (Table 1.1). This state is caused by a lesion involving the ventral
pons and, in 60% of cases, is due to basilar thrombosis. Functional neuroimaging
typically shows preserved supratentorial areas (with hypometabolism in the cer-
ebellum). Interestingly, significant hyperactivity has been observed bilaterally in
the amygdala of acute LIS patients, likely reflecting anxiety generated by the
inability to move or speak (stressing the importance of appropriate anxiety treat-
ment soon after diagnosis) [36]. Because patients with LIS have spontaneous
eyes opening, but are unable to speak or move the extremities, this state can be
confused with VS. On average, the diagnosis of LIS is not established until 2.5
months post-onset. There is evidence that family members tend to detect signs of
consciousness (55% of cases) prior to medical staff (23% of cases) [36]. Classic
LIS consists of complete paralysis of the orobuccal musculature and all four
extremities; however, vertical eye movements are spared, allowing nonverbal
communication through directional gaze. Perceptual functions are also usually
spared given that ascending corticospinal axons remain intact [34]. Bauer has
described multiple varieties of LIS, including the incomplete form in which
8 C. Schnakers and S. Majerus

there is residual motor activity (frequently, finger or head movements), and total
LIS, in which there is complete immobility including both horizontal and verti-
cal eye movements [37]. Total LIS cases have previously been reported but are
rare and request the use of neuroimaging or electrophysiological methods to
establish the diagnosis [38]. Data on life expectancy suggest that some patients
with LIS can live for more than 12 years while remaining in LIS. Surprisingly,
chronic LIS patients rate their quality of life similarly to the healthy population
[39]. In the absence of other structural or functional brain abnormalities, patients
with LIS are generally able to make independent decisions and communicate
their preferences through augmentative communication devices [36].

Patients with Covert Cognition

A different group of patients who are unable to show any behavioral sign of con-
sciousness but are able to respond mentally to active neuroimaging or electrophysi-
ological paradigms has been identified more recently (Fig. 1.1). In 2006, Owen and
colleagues reported the case of a non-communicative young woman with severe
brain injury. When performing a mental imagery task, her brain activity was similar
to the one observed in healthy controls [40]. Following this study, Monti and col-
leagues have tested 54 patients using the same paradigm. Only two patients diag-
nosed as being in a VS and three patients diagnosed as being in an MCS were able
to perform the task (9% of the group). One of these patients was able to answer
“yes” or “no” to autobiographical questions by using either motor or spatial imag-
ery [41]. Since then, a series of studies has been published about the detection of
willful brain activity in patients diagnosed as being in a VS, confirming the exis-
tence of patients with covert cognition [42].
It is tempting to think that these patients are with a severe form of LIS. However,
unlike LIS patients, patients with covert cognition present impaired connectivity
between subcortical and cortical, such as connections between the thalamus and the
primary motor cortex which will prevent the execution of willful motor actions [43].
According to a recent meta-analysis, covert cognition seems rare in VS (14% of
cases) but is more frequent in patients with traumatic brain injury than non-­traumatic
brain injury (32% vs. 19%) [42]. Future studies will nevertheless have to be multi-
centric in order to gather a sufficient amount of data to establish the profile of this
possibly new clinical entity.
As previous findings have shown the presence of communication in some
patients with covert cognition, recent studies have been trying to investigate the
interest of brain-computer interfaces (BCIs) in severely brain-injured patients
which may help those patients to communicate using neuroimaging or electro-
physiology [41, 44–47]. BCI paradigms should not be used for diagnostic pur-
pose. The tasks used to communicate are complex and could lead some patients
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 9

to be unable to respond even though they are conscious. Future studies will most
likely have to better understand residual cognitive functioning in those patients
before implementing successfully those augmentative communication tech-
niques [48].

Bedside Assessment

Diagnostic Accuracy

Differentiating MCS from VS can be challenging as voluntary and reflexive behav-

iors may be difficult to distinguish and subtle signs of consciousness may be
missed. The development of diagnostic criteria for MCS [25] should reduce the
incidence of misdiagnosis relative to the rates reported before these criteria were
established [6, 7]. However, a study comparing clinical non-standardized observa-
tion to examination with a standardized behavioral scale found that 41% of patients
believed to be in VS were misdiagnosed [8]. This study also found that the majority
of cases with an uncertain diagnosis were in MCS (89%), not in VS. Another 10%
diagnosed with MCS based on non-standardized examination had actually emerged
from this condition.
This high rate of misdiagnosis likely reflects several sources of variance. Variance
in diagnostic accuracy may result from biases contributed by the examiner, patient,
and environment. Examiner error may arise when the range of behaviors sampled is
too narrow, response time windows are over- or under-inclusive, criteria for judging
purposeful responses are poorly defined, and examinations are conducted too infre-
quently to capture the full range of behavioral fluctuation. The use of standardized
rating scales offers some protection against these errors [32], although failure to
adhere to specific administration and scoring guidelines may jeopardize diagnostic
accuracy. The second source of variance concerns the patient. Fluctuations in
arousal level, fatigue, subclinical seizure activity, occult illness (e.g., metabolic and
infectious encephalopathies), pain, cortical sensory deficits (e.g., cortical blindness/
deafness), motor impairment (e.g., generalized hypotonus, spasticity, or paralysis),
or cognitive disturbance (e.g., aphasia, apraxia, agnosia) also decrease the probabil-
ity of observing signs of consciousness [49]. Finally, the environment in which the
patient is evaluated may bias the assessment. Paralytic and sedating medications,
restricted range of movement stemming from restraints and immobilization tech-
niques, poor positioning, and excessive ambient noise/heat/light can all decrease or
distort voluntary behavioral responses.
Examiner bias can be greatly minimized by using standardized tools, but diag-
nostic accuracy is not always within the examiner’s control. This is particularly
troubling as clinical management, from rehabilitation to end-of-life decision-­
making, often depends on the behavioral observations of the examiner.
10 C. Schnakers and S. Majerus

Behavioral Scales

In light of the behavioral fluctuations that commonly occur in this population, eval-
uations should be repeated over time, and measures should be sensitive enough to
detect subtle but clinically meaningful changes in neurobehavioral responsiveness.
Conventional bedside assessment procedures and neurosurgical rating scales such
as the Glasgow Coma Scale [50] (GCS) have limited utility when used to monitor
progress in patients with prolonged disturbance in consciousness. These procedures
detect relatively gross changes in behavior and are not designed to distinguish ran-
dom or reflexive behaviors from those that are volitional. The Full Outline of
UnResponsiveness score (FOUR score) has greater sensitivity than the GCS for
detecting different levels of brainstem function in the acute stage of severe brain
injury [51], but because the FOUR score does not include a systematic assessment
of signs of consciousness [25], it may not capture the transition from VS to MCS
[52, 53]. Standardized rating scales have been devised for chronic disorders of con-
sciousness (DOC) to address these shortcomings, to assess a broad range of neu-
robehavioral functions, and to rely on fixed administration and scoring procedures.
Standardized neurobehavioral assessment measures tailored for DOC patients
include the Coma Recovery Scale – Revised (CRS-R) [54], the Coma-Near Coma
Scale (CNC) [55], the Western Neurosensory Stimulation Profile (WNSSP) [56],
the Western Head Injury Matrix (WHIM) [57], and the Sensory Modality Assessment
and Rehabilitation Technique (SMART) [58]. Although item content varies across
measures, all evaluate behavioral responses to a variety of auditory, visual, motor,
and communication prompts. All of these instruments have been shown to have
adequate reliability and validity; however, there is considerable variability in their
psychometric integrity and clinical utility. Of these measures, the CRS-R is the only
one that directly incorporates the existing diagnostic criteria for coma, VS, and
MCS into the administration and scoring scheme (Table 1.2). Giacino and col-
leagues (2004) compared the CRS-R to the DRS in 80 patients with DOC and found
that although the two scales produced the same diagnosis in 87% of cases, the
CRS-R identified ten patients in MCS who were classified as VS on the DRS [28].
There were no cases in which the DRS detected features of MCS missed by the
CRS-R. Schnakers and colleagues (2006) administered the GCS, CRS-R, and
FOUR score to 60 patients with acute (i.e., trauma center) and subacute (i.e., reha-
bilitation center) brain injury resulting in disturbance in consciousness [52]. Among
the 29 patients diagnosed with VS on the GCS, four were found to have at least one
sign of consciousness on the FOUR. However, the CRS-R detected evidence of
MCS in seven additional patients diagnosed with VS on the FOUR. All seven of
these patients showed sustained oriented eye movements, a clinical sign heralding
recovery from VS.
In 2010, the American Congress of Rehabilitation Medicine published the results
of the first evidence-based review of neurobehavioral rating scales designed specifi-
cally for patients with DOC [59]. Six of the 13 scales that qualified for the review
were recommended for use in clinical practice. The CRS-R received the strongest
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 11

Table 1.2 Coma Recovery Scale – Revised record sheet

Auditory function scale

4—Consistent movement to commanda
3—Reproducible movement to commanda
2—Localization to sound
1—Auditory startle
0—None
Visual function scale
5—Object recognitiona
4—Object localization: reachinga
3—Pursuit eye movementsa
2—Fixationa
1—Visual startle
0—None
Motor function scale
6—Functional object useb
5—Automatic motor responsea
4—Object manipulationa
3—Localization to noxious stimulationa
2—Flexion withdrawal
1—Abnormal posturing
0—None/flaccid
Oromotor/verbal function scale
3—Intelligible verbalizationa
2—Vocalization/oral movement
1—Oral reflexive movement
0—None
Communication scale
2—Functional: accurateb
1—Nonfunctional: intentionala
0—None
Arousal scale
3—Attentiona
2—Eye opening without stimulation
1—Eye opening with stimulation
0—Unarousable
Denotes MCS
a

Denotes emergence from MCS

b

recommendation (“minor reservations”), based on its performance across a panel of

psychometric quality indicators. The CRS-R is also one of the Traumatic Brain
Injury (TBI) Common Data Elements (CDE) suggested by the US National Institute
of Neurological Disorders and Stroke (NINDS) and the method of choice for moni-
toring recovery of consciousness in TBI research [60, 61].
12 C. Schnakers and S. Majerus

More Specialized Behavioral Assessments

Individualized Quantitative Behavioral Assessment

Clinicians involved in the care of MCS patients often encounter situations in which
the patients’ behavioral responses are ambiguous or occur too infrequently to clearly
discern their significance. These problems are often due to injury-related sensory,
motor, and arousal deficits. For this reason, a technique referred to as Individualized
Quantitative Behavioral Assessment (IQBA) was developed by Whyte and col-
leagues [62, 63]. IQBA is intended to address case-specific questions using indi-
vidually tailored assessment procedures, operationally defined target responses, and
controls for examiner and response bias. Once the target behavior (e.g., command-­
following, visual tracking) has been operationalized, the frequency of the behavior
is recorded following administration of an appropriate command, following an
incompatible command and during a rest interval. Data are analyzed statistically to
determine whether the target behavior occurs significantly more often in one condi-
tion relative to other conditions. For example, when the frequency of observed
behaviors is greater during the “rest” condition relative to the “command” condi-
tion, it is likely that the behaviors represent random movement rather than a pur-
poseful response to command.
IQBA can be applied across a broad range of behaviors and can address many
different types of clinical question. McMillan (1996) employed an IQBA protocol
to determine whether a minimally responsive, TBI patient could reliably communi-
cate a preference concerning withdrawal of life-sustaining treatment [64]. Responses
to questions were executed using a button press. Results indicated that the number
of affirmative responses to “wish to live” questions was significantly greater than
chance suggesting that the patient could participate in end-of-life decision-making.
McMillan’s findings were subsequently replicated in a second IQBA assessment
conducted by a different group of examiners [65].

Pain Assessment and the Nociception Coma Scale – Revised

Providing information as to whether a patient with DOC is in pain is important to

both clinicians and families. However, self-report is not an option in patients with
DOC because of the inability to communicate. The Nociception Coma Scale (NCS)
is the first standardized tool developed to assess nociceptive pain in patients with
severe brain injury. The first version of the NCS consisted of four subscales assess-
ing motor, verbal, visual responses as well as facial expression [66]. The NCS has
been validated in patients in intensive care and inpatient neurology/neurosurgery
units, rehabilitation centers, and nursing homes. In comparison to other pain scales
developed for non-communicative patients, the NCS has broader coverage and bet-
ter diagnostic sensitivity, suggesting that it is an appropriate assessment tool for this
1 Behavioral Assessment and Diagnosis of Disorders of Consciousness 13

population. The visual subscale was subsequently deleted since further analysis
showed that, following the application of noxious versus non-noxious stimuli, sig-
nificantly higher scores were obtained on the motor, verbal, and facial expression
subscales but not on the visual subscale. Using this revised version (NCS-R), a
cutoff score of 4 (sensitivity of 73% and specificity of 97%) has been defined as a
potential clinical threshold for detecting pain in patients with DOC [67]. Recent
findings have also shown a correlation between NCS-R total scores and the activity
in the anterior cingulate cortex (related to pain unpleasantness), reflecting further
the relevance of this scale when monitoring pain in patients with DOC [68]. The
scale has demonstrated good reliability and validity and currently exists in various
languages (i.e., French, English, Italian, Dutch, and Thai) [66, 67, 69–72]. Finally,
the interest of the NCS-R in assessing pain in a clinical setting has been investigated
recently [73]. Thirty-nine patients with potential painful conditions (e.g., due to
fractures, decubitus ulcers, or spasticity) were assessed with the NCS-R and the
GCS during nursing cares before and after the administration of an analgesic treat-
ment tailored to each patient’s clinical status. The NCS-R scores, but not the GCS
scores, were statistically lower during treatment when compared to the scores
obtained before treatment, providing further evidence that the NCS-R is an interest-
ing clinical tool specifically tailored for pain management.

Conclusion

Behavioral responses as well as brain activity differ among disorders of conscious-

ness. The detection of signs of consciousness can be challenging at the bedside
and the use of sensitive standardized scales is crucial. As misdiagnosis can lead to
serious consequences especially in terms of pain treatment and end-of-life
decision-­making, neuroimaging could constitute a complementary tool when
­disentangling VS from MCS patients. In the future, the development of conscious-
ness classifier based on residual brain activity or residual brain connectivity could
also substantially help clinicians and constitute an automated diagnostic tool. This
could particularly help for the detection of patients who are functionally
locked-in.

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