Disorders of Consciousness

Disorder of consciousness (DOC) is a state of prolonged altered consciousness, which can be categorized into coma, vegetative state, or minimally conscious state based on neurobehavioral function. The pathophysiology of DOC is poorly understood but recent advances in neuroimaging and advanced electrophysiological techniques may provide an improved understanding for the neural network involved with consciousness. The primary aim of DOC rehabilitation programs is to promote arousal while preventing secondary medical complications while providing education and training to families. Treatment interventions include both pharmacologic and nonpharmacologic programs, but there are currently no consensus treatment guidelines for individuals with DOC.

Key points

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Disorders of consciousness (DOC) are altered states of pathologic consciousness, which can be subdivided into coma, vegetative state, and minimally conscious state (MCS) based on neurobehavioral function.
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The Coma Recovery Scale-Revised assessment scale is recommended in DOC for clinical practice and research.
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Emergence from MCS is defined as reliable and consistent functional object use and functional communication.
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In a randomized, double-blinded, placebo controlled study, Amantadine improved functional recovery in patients with DOC.

Introduction

Annually, approximately 2.5 million people sustain a traumatic brain injury (TBI) in the United States, and more than 5.3 million people live with a TBI-related disability. TBI not only impacts the life of an individual and their family but also has a large societal and economic toll. The estimated economic cost of TBI in 2010, including direct and indirect medical costs, was approximately $76.5 billion. In addition, the cost of fatal TBIs and TBIs requiring hospitalization accounts for approximately 90% of the total TBI medical costs. Approximately 0.3% severe TBIs can result in Disorders of Consciousness (DOC). DOC is a state of prolonged altered consciousness, which can be categorized into coma, vegetative state (VS), and minimally conscious state (MCS). DOC can prove difficult to diagnose and treat and can result in increased burden of care for families and facilities. In this article, the authors review the definition, diagnosis, imaging, and treatment interventions for this difficult patient population.

Introduction

Consciousness

Historically, the concept of human consciousness has been difficult to describe on both a philosophic and a scientific level. Previous models often describe this phenomenon as a subjective experience, which consequently poses a diagnostic challenge in patients with a DOC. However, recent advances in modern medicine have allowed for improved survivability of acute brain injury and have secondarily imparted insight into the neural correlates of consciousness. Clinically, the 2 components that separate consciousness from unconsciousness are arousal and awareness. Wakefulness is a state of arousal, which can be assessed by the presence of eye-opening and brainstem responses. The depth of wakefulness can be evaluated objectively using measures such as the Glasgow Coma Scale. On a neuroanatomic level, arousal is mediated by the ascending reticular activating system of the upper brainstem. Activation of the cerebral cortex occurs with passage of sensory information from the upper brainstem via reticulothalamocortical and extrathalamic pathways. From a neurobiologic perspective, the conscious awake state is associated with a high energy demand and electrical activity within the corticothalamic system. This is further supported by electroencephalogram recordings (EEG), which show that increasing levels of arousal are associated with increased frequency of electrical activity in the cerebral cortex. Conversely, a decline in arousal is associated with reduction in excitatory neuromodulatory influences. The global deafferentation and disruption of the corticothalamic networks could explain the dysfunction in arousal seen in severe brain injuries. Awareness refers to the ability of an individual to respond to both external and internal stimuli in an integrated manner. It is inferred by command following and neurobehavioral assessment. On a neuroanatomic level, the connectivity of frontoparietal regions and the thalamus appears to play a role in the maintenance of consciousness. This is supported by functional MRI (fMRI) studies, which suggest dysfunctional cerebral connectivity in widespread areas of the frontoparietal networks in patients with DOC. In a healthy individual, an increase in arousal is associated with an increase in awareness in a linear fashion along the continuum of conscious states. A dissociation of these 2 components of consciousness is seen in pathologic states, such as in the VS and MCS.

Clinical entities

Brain Death

In 1995, the American Academy of Neurology (AAN) provided practice guidelines for the determination of brain death. They emphasized 3 clinical findings that indicate cessation of brain function: (1) coma (of known cause), (2) absence of brainstem reflexes, and (3) apnea. Before this determination, other causes for brainstem dysfunction should be excluded, including shock/hypotension, hypothermia, central nervous system depressants, spinal cord injury, and electrolyte and/or endocrine abnormalities. There is no consensus regarding the timing of follow-up testing, but clinicians must use judgment and perform serial evaluations to exclude the possibility for recovery. A diagnosis of brain death is ominous, and there have been no reports of neurologic recovery once determined by the 1995 AAN practice parameters.

Coma

A coma is a state of unconsciousness characterized by a lack of arousal and awareness. The defining clinical feature is the complete loss of spontaneous or stimulus-induced arousal. There is no eye opening, and EEG testing reveals the absence of sleep-wake cycles. Structural lesions usually involve diffuse cortical or white matter damage, or a brainstem lesion. Those who survive this stage will begin to awaken and transition to a VS/unresponsive wakefulness state (UWS) or MCS within 2 to 4 weeks.

Vegetative State/Unresponsive Wakefulness State

The VS is thought of as an unconscious, dissociative state of wakefulness without awareness. The patient’s eyes open spontaneously, and EEG testing reveals the presence of sleep-wake cycles. Patients may arouse by provocation or external stimuli, but they show no signs of conscious perception or deliberate action. Interestingly, these patients may perform stereotyped gestural movements such as yawning, chewing, crying, smiling, or moaning, but these are unrelated to context. The presence of wakefulness suggests preserved brainstem functioning, but the lack of awareness suggests an underlying cortical dysfunction. Likewise, functional neuroimaging has shown sensory stimuli will activate primary cortical areas, but not the higher order cortical areas thought necessary for awareness. With proper medical care, a patient in a VS can survive for many years.

Minimally Conscious State

The MCS is characterized by a severe impairment of consciousness, with evidence of wakefulness and partial preservation of awareness. Unlike the VS, there are discernible, purposeful behaviors that can be differentiated from reflexive behavior. Originally, these patients were categorized as VS, but there was evidence that they comparatively had meaningful improvement in outcomes. Therefore, in 2002 the Aspen Neurobehavioral Conference Workgroup established guidelines for MCS. The hallmark of MCS is inconsistent but reproducible, command following. The preservation of corticothalamic connections might explain why patients in MCS retain the capacity for cognitive processing. The patient may exhibit visual pursuit, emotional responses, and gestures to appropriate environmental stimuli, but are unable to functionally communicate their thoughts or feelings. Recently, a further subcategorization of the MCS was proposed by Bruno and colleagues, based on the complexity of observed behavioral responses, to minimally conscious plus (MCS+) and minimally conscious minus (MCS−).

Acute Confusional State

Once emerged from the MCS, patients continue to experience a transient period of disorientation and agitation. The full array of symptoms associated with the acute confusional state can also include irritability, distractibility, anterograde amnesia, restlessness, emotional lability, impaired perception, attentional abnormalities, and a disrupted sleep-wake cycle. A key pattern to this state is the day-to-day fluctuation of behavioral responses. The return of behavioral consistency despite situational stresses may indicate a resolution of this period.

Locked in Syndrome

Locked in syndrome is a rare condition characterized by intact consciousness and cognition, but with anarthria and quadriplegia. It is likely caused by damage to the ventral pons and the corticospinal/corticobulbar pathways, which communicate with the brainstem. Patients have intact sensation, and eye movements are spared, allowing for gaze-based communication. Over time, some patients may recover some control of the fingers, toes, or head. This atypical presentation, with lost speech and motor control, places these patients at risk for misdiagnosis as a DOC.

Clinical examination and quantitative assessment

A focused clinical examination is essential in distinguishing between DOC. Specifically, 7 domains should be tested and include sleep-wake cycles, awareness, motor skills, auditory function, visual function, communication, and emotional integrity ( Table 1 ). Sleep-wake cycles alone, detected through observation of intermittent eye-opening, will help differentiate someone in a VS from someone in a coma. The presence of awareness will further distinguish someone in a MCS from those in a vegetative one.

Table 1

Comparing features of coma, vegetative state, and minimally conscious state

	Sleep-Wake Cycles	Awareness	Motor	Auditory	Visual	Communication	Emotional
Coma	Absent	Absent	Reflexive	None	None	None	None
VS	Present	Absent	Purposeless/postures/withdraws to noxious stimuli	Startle	Startle	None	Reflexive
MCS	Present	Partial	Purposeful/localizes noxious stimuli	Localizes sound	Sustained fixation or pursuit	Intelligible verbal or gestural	Contingent responses

Adapted from Giacino JT, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002;58(3):349–53.

When testing the remainder of the domains, it is worth noting that certain caveats exist. First, yes/no responses can be given through direct verbal communication or through gestures such as a thumbs-up. These responses can be incorrect in regards to the questions asked, but they must be reproducible. Second, behavioral responses should demonstrate a definite relationship with their stimuli, such that reflexive activity cannot explain the response. For example, visual tracking of objects or persons, appropriate emotional responses to nonneutral content, and reaching for or grasping and manipulating objects. It is important to test a wide array of behavioral responses within the abilities of the patient and perform serial examinations to ensure accuracy. Last, it is imperative that a complete physical examination be done to provide insight for any findings that may obscure appropriate diagnosis, including but not limited to effects of sedative medications, aphasia, apraxia, motor impairments, or sensory deficits.

As the patient continues along the spectrum of recovery, emergence from an MCS would be evidenced by 2 distinct behaviors. The first is functional interactive communication, which would have to be demonstrated through means of correct yes/no responses to 6 situational questions on 2 consecutive examinations. Examples of such questions could include, “Are you lying in bed right now?” or “Am I holding a pen in my hand?” Again, responses can be gestural, written, or verbal. The second behavior is the functional use of 2 different objects that can be validated. Examples include the patient bringing a toothbrush to their mouth or pointing a remote to a television.

Behavioral assessment scales

Diagnosis of DOC is based on clinical observations and standardized neurobehavioral assessments. Neurobehavioral assessment scales require standardized scoring and ability to detect subtle signs of consciousness. Several scales have been developed to assess DOC patients. In 2010, a special task force, with the American Congress of Rehabilitation Medicine Special Interest Group in Disorders of Consciousness, reviewed 13 scales, of which 6 proved to be sensitive for detecting conscious awareness. Of those 6 scales, the Coma Recovery Scale-Revised (CRS-R) had the strongest content validity based on the Aspen criteria.

Coma Recovery Scale-Revised

The Coma Recovery Scale (CRS) was first described in 1991 and revised in 2004 (CRS-R). It has had multiple studies that have proved its sensitivity and reliability in diagnosis and monitoring progress in DOC patients. The CRS-R is a 23-item scale comprising 6 subscales, whose items are arranged hierarchically from reflexive to cognitively mediated processes. Subscales address visual, auditory, motor, oromotor, communication, and arousal categories. Emergence criteria are assessed by the communication (yes/no accuracy) and motor subscales (functional object use). Currently, this is the recommended scale because of its sensitivity and validity. Practitioner experience increases the interrater reliability and test-retest reliability. Training can be done by establishing interdisciplinary and particularly trained teams, using instructional videos, multicenter residency agreements, workshops, and video conferences.

Sensory Modality and Rehabilitation Techniques

Sensory modality and rehabilitation techniques or SMART was developed by Occupational Therapists at the Royal Hospital for Neuro-disability in London, United Kingdom as both an assessment and a treatment tool for patients in VS or MCS. SMART comprises 2 components. The formal component, conducted by the SMART assessors, includes the SMART Sensory Assessment and the SMART Behavioral Observation Assessment. The informal component consists of information from family and caregivers regarding observed behaviors and premorbid interests, likes, and dislikes. The SMART requires a 5-day training course to become an assessor and prior submission of a portfolio to gain access to the assessment tool.

Western Neurosensory Stimulation Profile

Western neurosensory stimulation profile (WNSSP) consists of 32 items, which assess patients’ arousal/attention, expressive communication, and response to auditory, visual, tactile, and olfactory stimulation. The WNSSP takes 20 to 40 minutes to administer and has shown internal consistency and standardized scoring and administration. It does rely on visual comprehension and tracking.

Wessex Head Injury Matrix

Wessex Head Injury Matrix (WHIM) is a 62-item scale, ordered in hierarchy, that assesses communication ability, cognitive skills, and social interaction. Assessment is by observation and testing tasks used in everyday life. The WHIM was created to follow a patient from emergence from coma to emergence from posttraumatic amnesia. It could take anywhere from 30 to 120 minutes to administer. To obtain the rating scale and training manual, there is a fee and training is required because it has been noted that interrater reliability and test-retest reliability relies on experience.

Sensory Stimulation Assessment Measure

Sensory stimulation assessment measure consists of presentation of standardized stimuli, including visual, auditory, tactile, olfactory, and gustatory. It is based on Glasgow Coma Scale responses of eye opening, motor, and vocalization. It is meant to follow a DOC patient long term and to be used with physical and neurological examinations. It takes 40 to 50 minutes to administer. It is useful in guiding treatment because the rater can evaluate what stimuli gives the most responses.

Coma Near Coma Scale

Coma Near Coma Scale consists of an 11-item test with specific and structured sensory stimulation for auditory, visual, olfactory, and tactile modalities. Vocalization and command response are also tested. It takes 15 minutes to administer and has good interrater reliability with self-training by reviewing instructions on the back of the form. It is good for evaluation but not guiding treatment.