Coma

Coma

Disorders of altered consciousness present a diagnostic dilemma to the clinician in the critical care setting. They represent a wide of range of pathology that can be systemic in nature or the result of structural or nonstructural intracranial pathology. Immediate evaluation and accurate diagnosis leading to lifesaving interventions are of paramount importance, as some causes of coma are irreversible. However, this can be a difficult task in critically ill patients. As such, the clinician must have an understanding of underlying disorders of consciousness and coma, the anatomy and pathophysiology leading to this disease state, a systemic approach in history taking and examination, and a rapid approach to workup and early therapeutic interventions.

Defining disorders of consciousness

Consciousness is defined as a state of full awareness of one’s self and relationship to the environment and is composed of content and arousal. ^, Whereas arousal is akin to one’s wakefulness and alertness, content of consciousness includes higher cerebral functional activity and awareness of one’s relationship to self and environment. As one might expect, content of consciousness is not possible without a certain level of arousal.

Coma is defined as a state of unresponsiveness. The patient lies in the bed with eyes closed without any purposeful response to external stimuli. Motor responses to deep painful stimuli may include flexor or extensor posturing, but comatose patients will not have any meaningful or purposeful movements, including localization.

Several other pathologic states of consciousness often referred to in the critical care setting demonstrate variable levels of arousal and awareness. These include lethargy, obtundation, stupor, clouding of consciousness, and delirium. Lethargic patients are severely somnolent, although they can be awoken by minimal stimuli; however, they will drift off to a state of drowsiness when continuous stimuli are not applied. Obtunded patients are similar to lethargic patients but have even less interest in their surroundings and slower responses to any sort of stimulation. These patients often exhibit more somnolence than lethargic patients. Stuporous patients require vigorous stimulation to be kept awake and if not stimulated will quickly fall into a state of unresponsiveness, and thus represent a state between awareness and coma. ^{, ,}

In contrast to patients requiring minimal or more extreme forms of stimuli for wakefulness, patients can also have clouding of consciousness, confusional state, and delirium. Clouding of consciousness refers to an altered state of consciousness that is defined by inattention and reduced wakefulness, whereas a confusional state tends to be more extreme and includes disorientation and inability to follow commands. Delirium and confusional state are often used interchangeably; however, delirium, by definition of the Diagnostic and Statistical Manual of Mental Disorders , 5th edn (DSM-V) is defined as altered consciousness with shifting attention or inability to focus and fluctuating course.

As one can imagine, these terms can be nebulous, oftentimes overlap, and are not always used in the appropriate clinical context to accurately describe a patient’s level of consciousness. Consequently, standardized scales have been developed to aid providers in measuring level of consciousness in patients. These scales serve as important tools when communicating with other healthcare providers. The scale most often used is the Glasgow Coma Scale (GCS) ( Table 43.1 ), which was initially used in trauma patients. The GCS measures three different criteria—eye opening, motor response, and verbal response—with lower scores indicating a poor examination. Typically, a score of 8 or below is indicative of coma. It is important to note that it is not possible to assess verbal response in intubated patients. Brainstem reflexes, an essential aspect of the examination in a comatose patient, are also not accounted for in GCS. With these shortcomings in mind, Wijdicks and colleagues developed the Full Outline of UnResponsiveness (FOUR) score ( Table 43.2 ). This scale includes eye response, motor response, brainstem reflexes, and respiratory patterns. The FOUR score provides more specific neurologic subtleties and consequently allows the clinician to differentiate between stages of herniation.

Differential diagnosis

Though the etiology of coma encompasses a wide range of causes, the differential diagnosis of coma is, in contrast, quite limited. Differentiating between coma and the following diagnoses requires an eloquent understanding of neuroanatomy in addition to precise and careful neurologic examination, differentiating between disorders of consciousness, and an appropriate time course for the specified disease process.

Locked-in syndrome results from damage to the ventral pons and the corticobulbar, corticospinal, and corticopontine tracts. The clinical presentation includes quadriplegia and anarthria with retained level of consciousness. Locked-in syndrome at times mimics as coma if a focused but thorough neurologic examination is not performed. In this case, careful inspection of the eye movements would reveal preservation of vertical eye movements when asking the patient to “look up.” However, failure to do so may result in an inaccurate diagnosis of coma. The causes of locked-in syndrome are numerous, including ischemic, hemorrhagic, traumatic, neoplastic, metabolic (central pontine myelinolysis), demyelinating (multiple sclerosis), and infectious; consequently, appropriate and swift diagnosis allows for timely therapeutic intervention if possible.

Persistent vegetative state refers to patients who have had a prolonged disorder of consciousness for longer than 1 month. Over time, patients may appear to have their eyes open, but remain unresponsive and unaware of external stimuli. The term persistent vegetative state , which can be pejorative, has been replaced by unresponsive wakefulness syndrome, which more specifically describes the patient’s clinical presentation. Typically, these patients have widespread cerebral structural injury and will have significant cerebral atrophy over time.

Akinetic mutism was first described by Cairns and colleagues in the 1940s as a state in which the patient does not move or speak; in the first case report, it was the result of an epidermoid cyst in the third ventricle. Since that time, akinetic mutism has been reported in bifrontal dysfunction or mesencephalic damage. Akinetic mutism is also associated with Creutzfeldt-Jakob disease and is one of the diagnostic criteria. In contrast to coma, patients with akinetic mutism are in fact aware and alert but are apathetic.

Brain death is death because of irreversible damage of the brain. Coma is one of the prerequisites for brain death, and neuroimaging must be consistent with irreversible brain injury. Additionally, all other confounding factors must be eliminated, including medication side effects, electrolyte imbalances, acid-base disturbance, endocrine abnormalities, hypothermia, and hypotension. Given that coma and brain death are intimately intertwined, it is essential to know when the comatose patient meets the prerequisites and criteria for brain death. In addition to the aforementioned prerequisites, the patient must have an examination consistent with brain death, including absent brainstem reflexes and absent motor response in all four limbs to noxious stimuli. Apnea testing must also be done. In certain circumstances, ancillary testing may be needed if components of the clinical examination or apnea testing cannot be performed, such as with massive facial trauma or hemodynamic instability. Ancillary testing includes four-vessel cerebral angiography, nuclear brain perfusion scan, electroencephalogram (EEG), and transcranial Doppler.

Psychogenic unresponsiveness or functional coma is a diagnosis of exclusion and is described as a state of unresponsiveness with preservation of brainstem reflexes. It can present in patients who have a history of depression, factitious disorders, or conversion disorders. Though a diagnosis of exclusion, the neurologic examination may alert the clinician to the fact that coma may not be organic in nature. Physical signs include resistance to eyelid opening and looking to the ground when turned on one side, termed “eye gaze sign.” Patients may not appear to have a normal vestibulo-ocular reflex (VOR), as they are able to fixate on a particular point with head turn. However, caloric stimulation with the instillation of cold water in the ear of a patient with psychogenic coma would cause eye deviation to the ipsilateral ear with contralateral horizontal nystagmus. This examination finding would be in contrast to organic coma, in which the VOR would be abnormal. Typically in psychogenic coma, EEG frequencies are consistent with patients in the awake state.

Anatomy and physiology

Discussion regarding the anatomy of consciousness would be remiss without briefly delving into the pivotal experiments of the 1930s and 1940s that helped synthesize understanding of the anatomic basis of consciousness. Constantin Von Economo studied patients during the epidemic of encephalitis lethargica and suggested that the upper brainstem and posterior hypothalamus controlled arousal. Bremer, while transecting the brains of cats, showed that transection through the midbrain caused a state of persistent sleep and EEG findings consistent with slow wave sleep; conversely, transection at the level of the cervicomedullary junction did not have any effect on arousal or sleep/wake cycles. Moruzzi and Magoun extrapolated on this premise further by showing that stimulating cholinergic neurons in the pontine tegmentum caused a state of arousal that was independent of the sensory pathways, including the medial lemniscus and spinothalamic tract. Destruction of the lesions in the reticular formation did not disrupt sensory pathways; disruption of sensory pathways did not cause a state of unarousal.

As such, the idea arose that two separate ascending pathways existed: ascending sensory pathways and an ascending reticular activating system (ARAS). Though the ascending sensory pathways and the ARAS terminate in the cerebral cortex (more specifically, in the primary sensory cortex and diffusely throughout the cortex, respectively), these ascending pathways synapse in different thalamic nuclei. The long ascending pathways synapse in the ventral posteromedial and ventral posterolateral nuclei, whereas the ARAS synapses in the intralaminar, midline, and reticular thalamic nuclei, also known as the nonspecific thalamic nuclei. As evidenced earlier, the ARAS either communicates or is located at multiple levels of the neuroaxis, including the afferent sensory pathways, the reticular formation in the brainstem, the thalamus, and the cerebral cortex. Pathology anywhere along this neuroaxis could contribute to alterations of consciousness.

Though underlying physiology is not entirely understood, neurons in the rostral pons and caudal midbrain have been implicated as major contributors to the pathways of the ARAS. Cholinergic nuclei in the pontine-midbrain junction that project to the thalamocortical neurons also modulate wakefulness. Additionally, norepinephrine in the locus coeruleus and serotonin in the raphe nuclei contribute to increasing levels of arousal. ^, These neurotransmitters of wakefulness and arousal are modulated by GABAergic and galaninergic inputs from the ventrolateral preoptic nucleus of the hypothalamus promoting onset of sleep. ^,

Etiology

With a more thorough understanding of the anatomic basis of coma, it is clear that coma arises from dysfunction of the bilateral cerebral hemispheres, the diencephalon, or the brainstem. Taking this into account, there are both nonstructural and structural causes of coma. Swift and accurate diagnosis allows for timely management that in fact may be vastly different. Therapeutic interventions can range from neurosurgical intervention to correction of electrolyte abnormalities in order to reverse the cause of coma or mitigate downstream injury.