Altered mental status at the extreme: Behavioral evaluation of disorders of consciousness

Abstract

Disorders of consciousness represent altered mental status at its most severe, comprising a continuum between coma, vegetative state/unresponsive wakefulness syndrome, minimally conscious state and emergence from minimally conscious state. Patients often transition between these levels throughout their recovery, and determining a patient’s current stage can be challenging, particularly in the acute care setting. Although healthcare providers have classically relied on a bedside neurological exam or the Glasgow Coma Scale to aid with assessment of consciousness, studies have identified s limitations of doing so. Neurobehavioral assessment measures have been developed to address these shortcomings, including the Coma Recovery Scale – Revised and others. Each behavioral metric has strengths as well as weaknesses when applied in the acute care setting. Here we review common assessment approaches, outline alternative measures for fine-tuning these assessments in the acute care setting, and highlight strategies for implementing these practices in an interdisciplinary manner.

Introduction:

Altered mental status exists along a broad spectrum of severity. A profoundly altered mental status may constitute a disorder of consciousness (DoC). Understanding the extent and stages of a DoC state has important implications for a patient’s level of awareness (which has ethical and psychosocial implications), prognosis, and care decisions. The lower an individual falls on the DoC continuum, the worse the long-term prognosis.¹ However, distinguishing between levels of DoC can be challenging, compounded by numerous different methods for doing so. Here we draw upon interdisciplinary perspectives from neurologists, physiatrists, and physical therapists to discuss behavioral evaluation methods in DoC. In doing so we identify the shortcomings of common assessment approaches, highlight assessment measures that improve the accurate stratification of DoC, and discuss strategies for implementing these methods into clinical practice.

Overview of Disorders of Consciousness Levels

Consciousness comprises arousal (wakefulness) and awareness (experience of one’s self and environment), where awareness depends upon arousal. Arousal is mediated by the ascending reticular activating system, which originates in the brainstem.^2–4 Arousal is also supported by the hypothalamus, which influences both sleep-wake cycles and autonomic function.⁵ DoC entails impairments in these components of consciousness, and can be divided into four general categories, including: coma, vegetative state, minimally conscious state and emergence from minimally conscious state (also described as post-traumatic confusional state in the context of traumatic brain injury). These categories represent parts of a continuum and patients will often transition between each level over time. A summary of the various stages on the DoC continuum can be found in Figure 1.

Figure 1:

Characteristics of DoC Levels with corresponding exam and CRS-R findings. (Bender et al., 2015; Bruno et al., 2011, 2012; Giacino, Kalmar, et al., 2004; Seel et al., 2010)

Coma is the lowest stage on the continuum. It is a state where a person is completely unconscious with no signs of wakefulness or awareness. There is also an absence of sleep-wake cycles on EEG.⁶ This state is commonly observed acutely after brain injury, often lasting no more than a few weeks before progressing to a vegetative state or death.⁷

The second stage is a vegetative state (VS), also known as the unresponsive wakefulness syndrome (UWS). The VS/UWS was historically defined as the “absence of any adaptive response to the external environment, the absence of any evidence of a functioning mind, which is either receiving or projecting information, in a patient who has long periods of wakefulness.” ⁸ Thus, characteristics of the VS/UWS include wakefulness with spontaneous eye opening, but only reflexive behaviors with no signs of conscious awareness of themselves or their environment. ^7,9,10 Sleep-wake cycles may be recovered.^{6–8 10,11,12}

The third stage is the minimally conscious state (MCS). A MCS classification implies subtle or inconsistent evidence of awareness of a person’s environment or themselves. ⁹ Given that awareness first starts to reemerge in the MCS, the transition from a VS to a MCS is often considered the recovery of consciousness. ¹³ In a study assessing which behaviors emerge first with recovery of consciousness after severe brain injury, visual pursuit was determined to be the most common initial sign of MCS. It was observed in 41% of patients recovering from either coma or VS/UWS. The second and third most common signs of transition from an unconscious state to a MCS included reproducible movement to command and automatic movement. ¹³ Improved prognosis is seen in patients who are diagnosed with a MCS as opposed to a VS/UWS.^14,15 Specifically, in a retrospective study comparing functional outcome across the first year post-injury between traumatic and non-traumatic brain injury, those patients who were diagnosed with a MCS compared to a VS/UWS at the time of admission to their rehabilitation-based coma intervention program had a significantly more favorable outcome at 3 months, 6 months and 12 months post-injury. In addition, those patients with severe disorders of consciousness who were initially diagnosed with a MCS had more consistent, sustained improvements in consciousness compared to those patients diagnosed with a VS/UWS.¹⁴

A MCS can be further subdivided into a minimally conscious state minus (MCS−) and a minimally conscious state plus (MCS+) ¹². The MCS− state implies the presence of non-reflexive, “nonlinguistic skills of conscious awareness,” including localization to noxious stimuli, visual pursuit in direct response to stimuli, object manipulation that demonstrates a “clear relationship between object, location and direction of reach, touching or holding objects in a manner that accommodates the size and shape of the object” ¹² and emotional behaviors appropriate to an environmental trigger but not to neutral stimuli. ^9,12 A MCS+ state implies the presence of limited expressive and receptive language function, including intelligible speech, verbal or gestural yes/no responses and command following. ^12,16

The fourth stage in the continuum is emergence from a minimally conscious state (eMCS). This stage implies consistent communicative behaviors and/or appropriate functional object use. Reliable communicative behaviors can be demonstrated through speech or writing, and can include command-following, intelligible verbalization, or yes/no responses. Functional object use is defined as the ability to use two common objects appropriately.⁹

A challenge that may arise is differentiating between a true DoC and other mimics. The locked-in syndrome, in which typically a lesion in the ventral pons prevents the ability to speak or move, is not considered to be a DoC because patients have preserved awareness despite impaired motor function. They are often able to communicate using eye movements due to preservation of supranuclear motor pathways ^10,11. Functional imaging techniques may potentially help with the identification of this condition¹². DoC may also be mimicked by akinetic mutism, a disorder of volition often caused by injury to the medial prefrontal cortex. Patients with akinetic mutism may appear awake, with eye opening and visual tracking (both spontaneous or environmentally stimulated). However they fail to follow commands, express emotions, verbalize or perform goal-directed behaviors, not because of an impairment in conscious awareness, but rather because of an impairment in the initiative necessary to execute those behaviors. ¹⁷

Pitfalls of the Traditional Neurological Exam

Many patients transitioning through the various stages of DoC are in an acute or critical care setting. The most common assessment of DoC is a traditional neurological exam. Often the traditional neurologic exam in this setting focuses on brainstem assessments (i.e., evaluation of brainstem reflexes) and cortical assessments (i.e., the presence or absence of purposeful behaviors). Commonly evaluated brainstem reflexes include the pupillary reflex, blink reflex, oculocephalic reflex, corneal reflex, gag reflex and cough reflex. Regularly evaluated purposeful behaviors include visual pursuit or fixation, command-following, and coherent responses to commands ^1,7.

However, studies suggest that traditional measures may be prone to error in assessing levels of consciousness. For instance, a retrospective study by Andrews et. al showed that 43% of patients had been misdiagnosed as being in a VS/UWS, when more detailed and standardized assessments (discussed below) suggested higher levels of consciousness. Of the misdiagnosed patients, 65% were noted to be severely visually impaired or blind. Thus, their lack of blinking or visual tracking were not reliable indications of a VS. ¹⁸ A subsequent study by Schnakers et. al. found similar results, with 41% of patients being misdiagnosed as being in a VS by physician evaluation, in both chronic and acute patients with traumatic brain injury. ¹⁹

In addition to the traditional neurological exam, a second measure commonly used in the critical care setting is the Glasgow Coma Scale (GCS). The GCS was one of the first scales to assess the depth of impaired consciousness. It focuses on three areas: motor response, verbal response and eye-opening response. The GCS score can be quickly acquired and easily communicated between providers. However, it is not a reliable assessment of consciousness in DoC. For example, though consistent visual pursuit is felt to be an indication of consciousness, this is not assessed by the GCS ^20,21. In addition, the GCS score is often reported as a total, which obscures the information necessary to deduce a level of consciousness. The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study sought to demonstrate the diagnostic errors that occur when using total GCS scores as a criteria for conscious diagnosis. Based on the TRACK-TBI data, GCS total scores of 3 to 6 were consistently associated with VS/UWS or coma while total scores of 14 and 15 were consistently associated with eMCS. The highest variability of DoC state diagnoses were seen between total GCS scores of 7 and 12. Though a score of 8 or less is often used to define coma, in a subset of 654 patients with a GCS of 8, 5% of patients were in a VS/UWS, 78% in a MCS−, 17% in a MCS+ and 0% were in an actual coma ²¹. Despite its practical utility, the GCS remains severely limited in accurately distinguishing between categories of DoC. ^1,7

Standardized Behavioral Assessments for DoC

Given the limitations of traditional assessments in DoC, there has been a critical need for standardized and detailed methods of evaluating DoC. In 2010, the American College of Rehabilitation Medicine (ACRM) released a systematic review of behavioral assessment scales for DoC. Key measures included the Coma Recovery Scale-Revised (CRS-R), Sensory Stimulation Assessment Measure (SSAM), Wessex Head Injury Matrix (WHIM), Western Neuro Sensory Stimulation Profile (WNSSP), Sensory Modality Assessment Technique (SMART), Disorders of Consciousness Scale (DoCS), and Coma/Near-Coma Scale (CNC). Of these assessment tools, the CRS-R was recommended to assess DoC with minor reservations. The SMART, WNSSP, SSAM, WHIM and DoCS were recommended with moderate reservations. ⁹

In 2018, the American Academy of Neurology (AAN), the American College of Rehabilitation Medicine (ACRM) and the National Institute on Disability, Independent Living and Rehabilitation Research (NIDILRR) released practice guidelines for DoC patients. The practice guidelines emphasized the importance of accurate diagnosis of the level of consciousness due to the implications for prognosis and treatment plans. They recommended using standardized neurobehavioral assessments over a traditional neurological examination alone, and reiterated the importance of using the 2010 ACRM recommended standardized assessments. ²² However, even these assessments have limitations in the acute and critical care setting, where there are greater time constraints and more dynamic patient conditions.

Coma Recovery Scale-Revised (CRS-R)

The CRS-R is a standardized neurobehavioral assessment tool developed for patients with DoC, and is currently considered the gold standard assessment for DoC (Figure 1). It can be used to establish a DoC diagnosis, monitor recovery, assist with prognostication, and evaluate treatment effectiveness. It includes six subscales that are hierarchically-arranged to delineate brainstem, subcortical, and cortical behaviors. Each subscale assesses a different domain, including auditory, visual, motor, oromotor, communication, and arousal functions. Each of these subscales receives a score, with a higher score indicating more advanced neurobehavioral function, and lower scores indicating reflexive behaviors;^23–26 total scores can range from a minimum of 0 to a maximum score of 23²⁷.^24,25 A total score of 10 or greater may support a diagnosis of MCS or eMCS, though level of consciousness is more precisely determined by the score of each subscale. The CRS-R also assesses expressive and receptive language function to differentiate between MCS+ and MCS−. ¹⁶ When the traditional bedside neurological assessment is compared to the CRS-R in detecting signs of consciousness, the CRS-R frequently outperforms the traditional neurologic exam because of its greater attention to purposeful eye movements. ¹⁹ The CRS-R has been shown to have high internal construct validity, ⁹ test-retest reliability and interrater reliability in multiple studies.^24,25 Multiple studies have shown that the initial CRS-R score and improvements within the first months are predictors of a better functional outcome.^14,28,29 Though most studies of the CRS-R have been conducted in the subacute or chronic settings, a growing number of studies have begun implementing the CRS-R in the acute setting after brain injury. Studies specifically conducted within the acute setting showed that improvements in CRS-R scores correlated with better outcomes at discharge.^30,31 A major limitation of the CRS-R in an acute or critical care setting is it takes to administer. For instance, owing to its comprehensive and detailed approach, a full CRS-R examination can require 15–30 minutes or longer given the complexities of administration in an intensive care unit (ICU). ^32,33

Full Outline of UnResponsiveness (FOUR) Scale

The Full Outline of UnResponsiveness (FOUR) scale was developed as an alternative to the GCS in evaluating DoC. The FOUR scale has four main components: eye responses, motor responses, brainstem reflexes and respiration patterns. The scale ranges from a score of 0 to 16, with a lower score implying more impairment. ³⁴ It was found to be superior to the GCS in identifying consciousness due to its inclusion of eye movements or blinking on command. ³⁵ This also improves its ability to differentiate between a VS/UWS and a locked-in-state. ^34,36 It is substantially quicker to administer than the traditional neurologic exam or CRS-R, requiring less than five minutes. Despite its speed of administration, the measure has good interrater reliability.^34,36 The absence of a verbal component allows for the more straightforward assessment of intubated patients.³⁴. It has been shown to predict mortality better than the GCS, likely due to its inclusion of brainstem reflexes and respiration, with a lower score implying a worse prognosis. ^36,37 Its inclusion of brainstem reflexes and respiratory patterns also distinguish it from the CRS-R, which does not assess these factors. While the FOUR scale help circumvent the time-intensiveness of the CRS-R, it does so at the expense of detail, and may less accurately differentiate between stages of DoC. For instance, while the FOUR scale can be administered more rapidly than the CRS-R, and can help identify a VS/UWS, it is less sensitive for detecting signs of MCS ³³. A study comparing the level of consciousness identified with the FOUR score, GCS and CRS-R, found that the FOUR score was superior to GCS in identifying a VS/UWS. The CRS-R, on the other hand, identified additional patients (some of whom were in the acute phase of brain injury) who showed visual fixation suggestive of a MCS ³⁵. Thus, abbreviated standardized neurobehavioral assessments such as the FOUR scale may be less suited to detecting subtle signs of consciousness.

Limitations of Existing Scales:

A common limitation of standardized neurobehavioral assessment scales in an acute care or ICU setting is the time they take to administer. For instance, owing to its comprehensive and detailed approach, a full CRS-R examination can require 15–30 minutes or longer given the complexities of administration in an ICU.^32,33 (Bodien et al., 2023; Wannez et al., 2017).While more abbreviated scales may help circumvent this challenge, they often do so at the expense of detail, and may less accurately differentiate between stages of DoC. For instance, while the FOUR scale can be administered more rapidly than the CRS-R, and can help to identify a VS, it is less sensitive for detecting signs of MCS. ³³ A study comparing the level of consciousness identified with the FOUR score, GCS and CRS-R, found that the FOUR score was superior to GCS in identifying a VS. The CRS-R, on the other hand, identified additional patients (some of whom were in the acute phase of brain injury) who showed visual fixation suggestive of a MCS. ³⁵ Thus, abbreviated standardized neurobehavioral assessments may be less suited to detecting subtle signs of consciousness.

Behavioral evaluations may be further limited by sedative agents used at the time of the assessments. The practice guidelines from 2018 emphasize that “level of consciousness cannot be assessed accurately during periods of low arousal.” ²² Many patients may be unable to tolerate decreased sedation for the duration of a complete standardized neurobehavioral assessment.³⁵ The CRS-R includes an arousal facilitation protocol (AFP), the aim of which is to increase the time for which the patient maintains arousal, which is defined as eye opening. The protocol is recommended to be implemented when a patient “exhibits sustained eye closure and/or stops following commands for a period of at least one minute.” Interventions recommended include deep pressure performed unilaterally to the face, neck shoulder and sternocleidomastoid muscle. ²³

Disorders of consciousness are typically attributed to acute brain injuries. However, toxic-metabolic encephalopathies (e.g., caused by renal failure, hepatic failure, or sepsis), or delirium, can mimic brain injury by suppressing consciousness and confound neurobehavioral assessments. In these situations, other measures can be used to identify delirium in the acute or ICU setting, including the Confusion Assessment Method for the ICU (CAM-ICU). Such measures are of limited utility for the assessment of consciousness, but may help indicate whether delirium is present. ³⁸

CRSR-FAST

In 2023, an abbreviated CRS-R, entitled the CRS-R For Accelerated Standardized Testing (CRSR-FAST), was developed to address the limitations of the CRS-R in a time-constrained ICU setting,³³ while preserving greater sensitivity for consciousness. The CRSR-FAST achieves faster administration times by focusing on CRS-R subscales most pertinent to differentiating between conscious and unconscious states, and incorporating “stop rules” triggered by behaviors indicative of consciousness. For example, the CRSR-FAST includes assessments of command-following, automatic motor responses, visual pursuit/fixation, localization to noxious stimulation and intelligible speech. The CRSR-FAST was validated in patients with acute traumatic brain injury in the ICU. There were few instances of diagnostic discordance between the CRS-R and the CRSR-FAST, which may be attributable to the limited reliability of a single assessment (see ‘Serial Exams‘ below). The results of the study suggest that the CRSR-FAST is a valid, reliable, and accurate measure for assessing consciousness in patients with TBI in the ICU. In addition, the average administration time was approximately 6.5 minutes, significantly shorter than the 15 to 30 minutes the CRS-R often requires. With its shorter administration time, it is not only conducive to the fast-moving ICU environment, but also to serial assessments for detecting subtle signs of consciousness. Through its adaptability across environments, the CRSR-FAST helps improve communication between acute care and rehabilitation providers. ³³

Individualized Quantitative Behavioral Assessment (IQBA)

Because the CRS-R is a standardized measure, some subscales may not reflect a patient’s true capabilities. The IQBA ³⁹ is a supplementary measure that can help individualize bedside assessments when discrepancies are observed between subscales of the CRS-R. The measure typically incorporates various assessment tools, such as direct observation and behavior rating scales, to gather comprehensive data about an individual’s behavior. The information collected from the IQBA helps to provide a more wholistic understanding of a person’s deficits, and allows for the development of a more tailored-approach to rehabilitation. While the IQBA alone cannot distinguish between VS/UWS versus MCS, some studies have suggested that this measure may be more likely to identify consciousness earlier and more consistently than the CRS-R alone.⁴⁰

Confusion Assessment Protocol (CAP)

The CRS-R has limited utility once a person reaches eMCS due to ceiling effects. Although eMCS indicates some level of recovery, these patients still may present with disorientation, impaired attention, memory deficits, or other cognitive impairments that limit functional capabilities. The CAP was designed to address issues of lingering orientation and/or cognitive deficits once a patient is able to follow commands and communicate. It is a succinct, repeatable measure including multiple components of a standard neurobehavioral exam. While it does not address DoC specifically, it can help monitor patient progress across the continuum of care as they recover from a confusional state. ^41,42

Motor Behavior Tool (MBT) and Revised Motor Behavior Tool (MBT-r)

The MBT ⁴³ was developed to help identify subtle motor behaviors indicative of consciousness that otherwise may be overlooked by the CRS-R, particularly for patients in the acute setting. A preliminary study found that the original 10-item MBT, in conjunction with the CRS-R findings, significantly improves the evaluation and predictability of outcomes in the early, acute stages of recovery from brain injury. A revised version of this measure, the MBT-r, ⁴⁴ was developed with a simplified scoring system as a stand-alone measure that can be used complement the CRS-R. This measure includes seven items that indicate positive motor signs (behaviors that reflect consciousness) and two items that indicate negative motor signs (reflexive behaviors). In contrast to the CRS-R, both the MBT and MBT-r account for non-systematized hypokinetic movements, initiation of intentional motor responses, and facial movements induced by noxious stimuli, such as grimacing. ⁴³ One study, although limited by a small sample size, indicated that up to 70% of patients classified as VS/UWS on the CRS-R demonstrated signs of residual cognition on the MBT-r. ⁴⁴ Another study indicated that the MBT-r may be more likely to discriminate patients with true DoC from those with clinical cognitive-motor dissociation. ⁴⁵ While neither the MBT nor MBT-r can definitively diagnose individuals as VS/UWS, MCS, or eMCS, positive findings on either measure may identify early, subtle signs of residual cognition which may be missed by the CRS-R.

Sensory Modality Assessment and Rehabilitation Technique (SMART)

The Sensory Modality Assessment and Rehabilitation Technique (SMART) is another assessment tool for DoC that incorporates serial examinations in its design. It includes two formal assessments in the form of the SMART Behavioral Observation Assessment and SMART Sensory Assessment, as well as an informal assessment of other observed behaviors. During the SMART Behavioral Observation Assessment, the examiner quietly observes the patient for a ten-minute period to document reflexive, spontaneous and purposeful behaviors. The subsequent SMART Sensory Assessment incorporates a graded measure of the patient’s motor, sensory and communicative responses to a structured sensory program. Eight modalities are tested within the SMART Sensory Assessment, which includes sensory stimuli (visual, tactile, auditory, olfactory, gustatory) and a physical assessment (wakefulness, functional motor ability, communicative ability). Each modality is scored on a five-point scale, with level 1 indicating no response and level 5 indicating a discriminating response. A consistent level 5 response in any sensory modality indicates an MCS. The SMART assessment tool has been shown to have excellent test-retest reliability. ⁴⁶ It is recommended that the SMART is administered ten times within three weeks, to maximize sensitivity. While studies have shown its validity and reliability ⁴⁶, its main limitation is its duration, requiring approximately 60 minutes to complete, which may not always be feasible in an ICU setting. In addition, it requires examiners to complete a five-day course in the United Kingdom, which limits its generalizability.^46,47,46,46

Limitations of scales

Behavioral evaluations may be limited by sedative agents used at the time of the assessments. The practice guidelines from 2018 emphasize that “level of consciousness cannot be assessed accurately during periods of low arousal.” ²² Many patients may be unable to tolerate decreased sedation for the duration of a complete standardized neurobehavioral assessment. ³⁵ The CRS-R includes an arousal facilitation protocol (AFP), the aim of which is to increase the patient’s arousal, identified by eye opening. The protocol is recommended to be implemented when a patient “exhibits sustained eye closure and/or stops following commands for a period of at least one minute”.²³ Interventions recommended for the AFP include deep pressure delivered to the face, neck, shoulder and sternocleidomastoid muscle.²³

Disorders of consciousness are typically attributed to acute brain injuries. However, toxic-metabolic encephalopathies (e.g., caused by renal failure, hepatic failure, or sepsis), or delirium, can mimic brain injury by suppressing consciousness and confounding neurobehavioral assessments. In these situations, other measures can be used to identify delirium in the acute or ICU setting, including the Confusion Assessment Method for the ICU (CAM-ICU). Such measures are of limited utility for the assessment of consciousness, but may help indicate whether delirium is present. ³⁸

Multidisciplinary Approach

Patients with DoC in the acute or ICU setting often have an extensive and multidisciplinary clinical care team. Communication and collaboration between the various providers allow for more coordinated and effective care, and avoids the miscommunications that can otherwise distress and confuse patient families. The 2018 practice guidelines highlight the importance of a team approach between healthcare providers, including but not limited to physicians, physical therapists, occupational therapists, speech-language pathologists, social workers and nutritionists for the care of patients with DoC ²². Such coordination applies equally to the behavioral evaluation of DoC. Each discipline often has unique perspectives and approaches to DoC evaluation. For example, neurologists may have an aptitude for elements of the neurologic exam, such as brainstem assessment. Physiatrists may have perspective on what behavioral signs imply for long-term recovery and may make recommendations regarding potential modalities or medications that could augment a patient’s recovery. Speech-language pathologists may screen for aphasia that could be complicating assessment or develop crucial means for non-verbal communication. Physical therapists and occupational therapists often have the dedicated time with patients to complete more detailed evaluations and the expertise for leveraging their findings towards therapeutic strategies (Table 1). Ensuring ample opportunities for these various team members to share their findings, resolve discrepancies, and come to consensus regarding the interpretation and implications of the evaluations, is vital to the care of patients with DoC in the acute and ICU setting.

Table 1:

Summary of Rancho Los Amigos-Revised scale with corresponding Disorder of Consciousness (DoC) levels and corresponding Rehabilitation Considerations at Different Levels of Cognitive Recovery

Rancho Level	Rancho Level Description	DoC Level	Common Treatment Location(s)	Implications for Treatment
				Common Medical Issues/Interventions	Example Therapy Interventions	Behavioral Measures
Level I—No Response: Total Assistance	Lack of response to external stimuli (visual, auditory, tactile, noxious)	Coma	EMS/ICU/Acute care hospital	Dysautonomia and PSH (Early stage post-TBI)79,80	Range of motion and positioning important to avoid contractures Sensory stimulation 70,71,75	CRSR-FAST CRS-R FOUR GCS
Level II—Generalized Response: Total Assistance	Generalized, non-localized reflex response to painful stimuli Responds to environmental stimuli with generalized body movements Inconsistent	VS/UWS or MCS−	ICU/Acute care hospital	PSH (Early stage post TBI) Consider neurostimulants to promote dopamine signaling (e.g., amantadine 30,66,67, methylphenidate69) vs. GABA-A agonist (e.g., Zolpidem73,74)	Sensory Stimulation 70,71,75 Music Therapy 70,71,75	CRSR-FAST CRS-R FOUR GCS
Level III—Localized Response: Total Assistance	Withdrawal or vocalization to noxious stimuli (localization noted) Turn towards or away from auditory stimuli Tracks moving objects when within visual field Responds inconsistently to commands, often with delays May respond to familiarity (friends, family) more so than strangers	MCS− or MCS+	Acute care hospital, SAR, DoC Program, IRF or LTACH	PSH (Early stage post TBI) Consider neurostimulants as detailed above	Sensory Stimulation 70,71,75 Music Therapy 70,71,75	CRSR-FAST CRS-R FOUR GCS
Level IV—Confused, Agitated: Maximal Assistance	Alert and heightened state Restless with purposeful pulling at restraints and tubes Bizarre, incoherent, inappropriate or nonpurposeful behavior Impaired short-term recall Limited attention	MCS+ or eMCS	Acute care hospital, IRF, SAR	Agitation management essential for patient and staff safety Avoid overstimulation of the patient (limit visitors, space out therapy sessions, minimize loud sounds or bright lights) PSH may remain an issue Pharmacological management of agitation (e.g., beta blockers72) Sleep-wake cycle promotion (light during the day, encourage patient to remain awake during the day and sleep at night, sleep hygiene practices, potentially pharmacologic interventions)	May require an outlet to deal with excess energy (Enclosure bed, etc) Active and consistent engagement with physical therapy, occupational therapy or speech therapy Re-orientation techniques, ideally with same team members Alternative modes of communication to decrease agitation	Agitated Behavior Scale81 GOAT O-Log82
Level V—Confused, Inappropriate, Not Agitated: Maximal Assistance	Random, nonpurposeful responses with stimuli Consistent following of simple commands Impaired attention and memory (new information not retained)	eMCS	IRF, SAR	Consider neurostimulants as detailed above	Locked unit to prevent elopement Consistent reorientation	Berg83 DRS84 FIM85-FAM86
Level VI—Confused, Appropriate: Moderate Assistance	Situation appropriate, goal-directed responses often with a reliance on external input for direction Able to recall relearned tasks, less so new ones Short term memory impaired	eMCS	IRF, SAR, outpatient rehabilitation (start of community re-entry)	Consider neurostimulants as detailed above	Impulsivity an issue because unaware of safety risks and limitations	Berg DRS FIM-FAM
Level VII—Automatic, Appropriate: Minimal Assistance for Activities Daily Living Skills	Behaves appropriately in familiar settings Able to recall new things, but at a slower rate Automatically performs daily routines Initiates social interactions, but with impaired judgement Unable to recognize inappropriate social interactions	eMCS	IRF, outpatient rehabilitation (focus on community re-entry)	Consider neurostimulants as detailed above	Often has a more superficial understanding of their condition, but do not typically recall the details which could compromise their safety awareness	Berg DRS FIM-FAM
Level VIII—Purposeful, Appropriate: Standby Assistance	Consistently oriented to person, time and place Able to focus on and complete tasks for 1 hour despite distractions in the environment Short term memory improved, with ability to recall recent events and integrate with long term memory Aware of impairments and disabilities when interferes with activities, but will need standby assistance to problem solve Able to realize inappropriate social interactions while it is occurring and able to problem solve with minimal assistance	eMCS	Outpatient rehabilitation including vocational and day programs with focus on community re-entry and social skills	Depression more likely to appear as awareness of deficits increases	Reinforce use of memory aides and other adaptive techniques	Berg DRS FIM-FAM
Level IX—Purposeful, Appropriate: Standby Assistance	Able to change between tasks and perform them accurately for at least two hours Able to initiate and complete familiar daily tasks, including grooming, household activities, work activities and leisure activities. Able to complete unfamiliar grooming/personal, household, work and leisure activities with assistance if necessary Accurately estimates their abilities	eMCS	Outpatient rehabilitation including vocational and day programs with focus on community re-entry and social skills	Supported volunteering and/or employment	Emphasis on routine and consistency	Berg DRS FIM-FAM
Level X—Purposeful, Appropriate: Modified Independent	Able to tolerate multiple tasks at once regardless of environment, but may require periodic breaks. Able to independently manage memory devices Able to initiate and complete both familiar and unfamiliar personal, household, work, community, leisure tasks, but may require more time or compensatory strategies to complete Able to anticipate the impact any disabilities or impairments may have on activities of daily living and able to problem solve prior to an issue arising Able to independently consider repercussions of actions, but may require more time to make decisions Social acumen improved and able to recognize emotions or needs of others Irritability, specifically when under stress Social interaction appropriate throughout various situations	eMCS	Outpatient rehabilitation, community programs, day programs	Graduated return to work	Subtle impairment in abstract reasoning can be seen	Berg DRS FIM-FAM

VS/UWS = Vegetative State/Unresponsive Wakefulness Syndrome, MCS = minimally conscious state, eMCS = emerged from minimally conscious state or no longer has a DoC, IRF = Acute Inpatient Rehabilitation Facility, LTACH = Long Term Acute Care Hospital, SAR = Subacute Rehabilitation, PSH = paroxysmal sympathetic hyperactivity, GOAT=Galveston Orientation and Amnesia Test, PTA=Post-Traumatic Amnesia, O-Log=Orientation Log, DRS=Disability Rating Scale, FIM-FAM: Functional Independence Measure-Functional Assessment Measure, ADLs: Activities of Daily Living ^7,60,62–78

Serial Exams

DoC states are dynamic disorders, as levels of consciousness typically fluctuate, and may improve or worsen, over time. Providers may need to identify subtle changes in a patient’s behavior to detect evidence of improvement.⁴⁸ Serial detailed behavioral assessments are therefore often critical to capture changes, and to reflect the best possible level of consciousness. Guidelines have stressed the importance of frequent assessments to avoid misdiagnosis. ^9,22 One study investigated the number of DoC assessments necessary to minimize misdiagnosis. ³² Experienced CRS-R examiners completed a series of six CRS-R exams for 123 patients over a ten day period, concluding that at least five exams are necessary to minimize misdiagnosis risk. Conversely, fewer examinations often lead to underestimations of level of consciousness. For example, of the 62 patients initially diagnosed as VS/UWS, 35.5% were ultimately diagnosed as MCS after serial assessments. The key behaviors observed with serial assessment that changed the DoC diagnosis included visual pursuit, visual fixation, automatic motor reactions, pain localization and object localization. ³² It is important to note that this study was conducted in a chronic DoC population. Patients in the acute stage of brain injury often exhibit even more pronounced fluctuations in consciousness – owing to factors such as rapid recovery, intermittent sedatives, and toxic-metabolic insults – making serial assessments all the more critical in this population. The multidisciplinary approach described above may facilitate the feasibility of serial assessments, to ensure that level of consciousness is appropriately assessed.

Non-behavioral methods of assessing consciousness in DoC

Behavioral evaluations remain the mainstay of assessment in DoC. However, it is plausible that a subset of patients who appear unconscious on behavioral evaluation may demonstrate evidence of consciousness through non-behavioral techniques. Technologies such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have demonstrated that a portion of unresponsive patients can willfully modulate their brain activity in response to command, a phenomenon termed covert consciousness, or cognitive-motor dissociation. ^49,50

fMRI is a neuroimaging technique that allows for the measurement and localization of brain activity in response to stimuli. Activation of high-order cortical areas has helped predict functional recovery in chronic DoC patients. ⁵¹ In addition, fMRI may be used to aid in DoC diagnosis: after delivering commands to patients during the scan (e.g., “imagine moving your hand”), fMRI can help detect the willful modulation of brain activity in response (e.g., activity in the supplementary motor area), that reflects the preservation of consciousness.⁵² This technique was recently studied in a subset of acute DoC patients in the ICU. While the study population was small, it showed that fMRI could be used for diagnostic and prognostic purposes in the acute DoC population.⁵¹ In another study which assessed task-based fMRI and EEG findings in the ICU, if was found that these two modalities could detect higher order cortical function and command following, thereby allowing for detection of consciousness.⁵³ The information fMRI provides may aid with decisions and discussions regarding goals of care during the acute ICU period. ^51,54,55 However, while a positive test may aid to show consciousness, a negative test cannot be used to definitively rule out consciousness given their current investigational nature.⁵⁵

EEG can also help detect evidence of willful modulation of brain activity. In a prospective study conducted in unresponsive patients with acute brain injury in the ICU, EEG was collected along with the delivery of commands to detect cognitive-motor dissociation. ⁵⁶ In these patients, 15% had evidence of brain activation on EEG in response to commands consistent with cognitive-motor dissociation, at a median of four days post-injury. In turn, 50% improved to a state where they were able to overtly follow commands before discharge (compared to 26% of patients without cognitive-motor dissociation), and 44% at 12 months were able to function independently for 8 hours (compared to 14% of patients without cognitive-motor dissociation). Patients who were found to have early cognitive-motor dissociation also demonstrated a more rapid functional recovery than those who did not.⁴⁹ Thus, identification of cognitive-motor dissociation may have implications for rehabilitation potential, and for goals of care discussions.

Emerging guidelines have suggested that such technologies may be used to supplement behavioral evaluations to comprehensively evaluate level of consciousness in DoC. ^22,57

Translating assessment to management

Determining a patient’s level of consciousness is often inherently valuable, as it indicates the extent of what a patient may experience, which may influence the manner in which family and providers interact with them, and the ways in which patients are included in decision-making. However, there are numerous other implications to these assessments of DoC as well.

The level of consciousness determined with behavioral assessment has prognostic implications, where hospitalized patients with greater levels of consciousness demonstrate more robust recoveries over time ^14,15. A study of patients with a DoC less than 90 days in duration showed that the initial consciousness level has high prognostic value ²⁹. In a subset of 67 patients in a VS/UWS or MCS, the survival rate was significantly higher in the MCS population compared to the VS/UWS. In addition, when comparing the patients who were initially diagnosed as VS/UWS compared to those who were initially diagnosed as MCS, the VS/UWS group had significantly poorer outcomes. These patients were assessed after a mean duration of 527 days, with the follow up duration ranging from 196 days to 886 days. Thus, an accurate determination of DoC diagnosis in the acute period has important implications for goals of care discussions. ^14,15,29

^14–16,29Level of consciousness may influence disposition options once patients are medically ready for hospital discharge. Acute inpatient rehabilitation facilities, disorders of consciousness rehabilitation programs, long-term acute care hospitals, skilled nursing facilities and hospices all have specific admission requirements, which sometimes relate to level of consciousness. Proper communication of level of consciousness to these facilities helps ensure that patients are discharged to a facility that can best accommodate them.

Level of consciousness may influence treatment strategies. Physiatrists often use the eight stages of the Rancho Los Amigos Levels of Cognitive Functioning Scale (commonly referred to as the Rancho Los Amigos Scale or Ranchos) or the ten stages of the Rancho Los Amigos-Revised scale when assessing patients with traumatic brain injury (TBI). There is overlap between the Ranchos levels and the DoC states (Table 1). This serves as a scale that not only standardizes communication between rehabilitation clinicians but also guides treatment and therapy plans. ^7,58–61 For instance, a patient with a Ranchos level IV following a TBI would exhibit confusion and behavioral disruption. They may benefit more from a dopaminergic agent aiming to potentially reduce confusion, such as amantadine. ⁶² Other neurostimulant choices to consider include those that target serotonergic, glutaminergic or cholinergic pathways. A thorough assessment thus has implications on what neuropharmacologic interventions, therapy techniques or modalities may be pursued. Table 1 includes a brief summary of potential treatment options based on level of consciousness and its corresponding Rancho level. The proposed interventions and assessment measures seek to assist in decision making, but are not intended as a definitive fully comprehensive guide (Table 1).

Conclusion

DoC represent the most severely altered forms of mental status, and behavioral assessments are key to appropriately determining patients’ level of consciousness in this condition. Time constraints, coupled with dynamic changes in consciousness, sedation, and medical stability, all complicate these assessments in the ICU and acute care setting. Thus, standardized and serial testing is critical to ensure that these evaluations are rigorous and reflect the highest level of consciousness of which patients are capable. The scales used to standardize these assessments continue to be developed to better adapt to this unique patient population in this unique care setting. Though these behavioral assessments may increasingly be supplemented by evolving technologies to probe brain function in alternative ways, behavioral assessments remain foundational to these evaluations, and have numerous critical ethical, psychosocial, logistical, prognostic, and therapeutic implications. Multidisciplinary collaboration between disciplines such as neurology, physiatry, physical therapy, occupational therapy and speech-language pathology will ensure that assessments are acquired rigorously, are communicated effectively, and appropriately guide patient care.

Figure 2:

Algorithm for neurobehavioral assessment and non-neurobehavioral assessment of consciousness in an acute or ICU setting^1–9.