Coma is the absence of consciousness.
This state of unarousable unconsciousness includes the failure of eye opening to stimulation, a motor response no better than simple withdrawal-type movements, and a verbal response no better than simple vocalization of nonword sounds. This presupposes that the motor pathways and systems that would allow a conscious patient to respond are intact.
Full consciousness is an awake state in which one is aware of oneself and the environment, including the ability to perceive and interpret stimuli and to interact and communicate with others in the absence of motor deficits.
Basic alerting and wakefulness is a function of the ascending reticular activating system (ARAS).
Awareness is more complex and incompletely understood. It has multiple hierarchies (the highest probably being self-awareness and apperception) and components (e.g., perception, memory, attention, language and other symbolic coding, emotion, motivation, response selection). These components of awareness, and full conscious awareness itself, are now thought to relate to the integrated action of networks of cerebral cortical regions. In the assessment of conscious awareness, the Coma Recovery Scale-Revised (CRS-R) is useful in grading and tracking the level of consciousness.
The irreversible, total destruction of all brainstem functions, including the capacity for alertness, cranial nerve functions, and apnea (UK), or all brain function (whole brain death in US).
Brain death must never be diagnosed without an etiology.
Vegetative state (unresponsive wakefulness syndrome [UWS])
The complete loss of awareness with preserved wakefulness and wake-sleep-cycles. Thalamocortical function is severely disrupted. VS is commonly due to severe cerebral cortical damage (usually by anoxia-ischemia after cardiac arrest or less commonly by hypoglycemia), by damage to the white matter of the cerebrum (most commonly related to diffuse axonal injury from traumatic brain injury), or thalamic damage (by anoxia-ischemia or structural lesions such as tumors or strokes). A new term, UWS, is gradually replacing VS as some patients who are behaviorally unresponsive may have “covert awareness”, as revealed by specialized testing such as functional magnetic resonance imaging (fMRI).
Minimally conscious state (MCS)
The preservation of 1 or a very few elements of awareness: for example, behaviorally fixating or following with the eyes and reaching purposefully for an object.
More isolated/focal aspect of impaired awareness in which attention or selection and maintenance of mental concentration is the key feature.
Alerting/wakefulness is preserved to a large degree.
More isolated/focal aspect of impaired awareness most commonly seen with lesions of the nondominant parietal lobe or prefrontal cortex.
Alerting/wakefulness is preserved to a large degree.
Diffuse disturbance of cerebral function in the absence of overt parenchymal inflammation or structural abnormality.
There are numerous encephalopathies due to electrolyte disturbances, disturbances in thyroid function, inborn errors of metabolism (e.g., porphyria, mitochondrial disorders), organ failure (e.g., hepatic encephalopathy), systemic inflammation (e.g., due to burns), and cardiac arrest (anoxic-ischemic encephalopathy). Most of these cause reversible, functional dysfunction of the ARAS and cause a more diffuse disturbance without localizing signs.
Includes brain abscess, tumor, intracerebral hemorrhage, and trauma with epidural or subdural hematoma.
Depending on the case mix, mass lesions causing coma are common, especially in centers with patients with trauma, cancer, or stroke, and even in general hospitals.
It is important to recognize early phases of herniation syndromes (caused by shifts of brain structures from one compartment to another), and to investigate and treat before irreversible damage occurs. Consciousness is impaired due to compression of ARAS components.
In subfalcine herniation, the midline structures of the supratentorial space are laterally displaced, causing pressure on the thalamus and progressive impairment of consciousness with or without hemiparesis, and oculomotor palsy in later stages.
With transtentorial herniation there is downward displacement of the uncus (uncal herniation) or diencephalic structures (thalamus and hypothalamus) through the tentorial opening. This causes brainstem compression with early oculomotor palsy often before loss of consciousness.
Tonsillar herniation through the foramen magnum compresses the caudal medullary respiratory center, causing respiratory arrest and brain death.
Central (diencephalic) herniation is said to be common. Compression of the midbrain produces irreversible bilateral oculomotor palsies in later stages.
Rostrocaudal deterioration of brainstem function occurs with brainstem distortion affecting microvascular perfusion of tissue. Loss of consciousness is typically abrupt with cranial nerve palsies.
Disorders mimicking comas
Locked-in state is when consciousness is preserved but motor output is impaired (e.g., due to basis pontis lesions, severe polyneuropathies such as Guillain-Barre syndrome or pharmacologic paralysis).
Psychogenic unresponsiveness relates to lack of responsiveness due to psychogenic causes, in the absence of any toxic, metabolic, inflammatory, or structural damage to the brain (e.g., pseudocoma, pseudoseizure, psychogenic seizures).
Syncope (fainting) is a transient coma due to the temporary reduction of global brain perfusion, which can be due to cardiac etiologies, vasomotor etiologies, orthostatic hypotension, or pulmonary embolism.
Seizures produce transient coma due to epileptiform discharges in the brain, either as absence/petit mal seizures (bifrontal or diffuse cortical and thalamic involvement), focal unaware seizures (usually of temporal lobe origin, associated with diffuse limbic involvement and cerebral cortical inhibition), or generalized convulsive seizures (with seizure discharges involving both cerebral hemispheres and brainstem structures). Coma can be prolonged in status epilepticus (e.g., nonconvulsive status epilepticus as diagnosed by EEG). Convulsive movements and incontinence can occur, especially with generalized tonic-clonic seizures.
Concussion is the transient impairment of consciousness due to a forceful displacement of the brain (e.g., by a blow to the head or sudden acceleration or deceleration).
Alerting or arousal is a function of the ARAS. Arousal to wakefulness is a prerequisite for awareness. This arousal system is anatomically represented by several structures in the rostral brainstem tegmentum, the diencephalon, and projections to the cerebral cortex. Principal among these are acetyl choline-producing neurons in the rostral brainstem. These project rostrally in 2 major pathways that also contribute to cortical arousal:
A dorsal pathway that synapses with the midline and nonspecific thalamic nuclei, which then send a glutaminergic projection to large areas of the cerebral cortex
A ventral pathway from the rostral brainstem tegmentum that reaches the basal forebrain, especially the posterior hypothalamus, where axon terminals act on neurons that synthesize histamine, hypocretin, or orexin.
The ARAS is a complex system with some redundancy of pathways that are involved in arousal and maintenance of wakefulness. This may explain the recovery of the arousal system after initial coma, almost always within 3 weeks from coma onset in most patients. As a corollary, disorders cause impaired consciousness by impairing the function of a significant component of the ARAS.
Although transient episodes of unconsciousness (e.g., faint, seizure) are common and account for about 5% of emergency room visits, in-hospital consultations for coma constitute only 0.02% of admissions in England. Adult men and women are almost equally affected. The mean age is 57 years, although >35% of patients with coma are >75 years of age.
Prevention and management
Initial management steps include airway, breathing, and circulatory (ABC) support. In the unresponsive patient, airway protection is paramount.
Clinical assessment tools for patients with impaired consciousness, include the Glasgow Coma Scale and the Full Outline of UnResponsiveness (FOUR) scoring system; the latter has advantages in intubated patients.
Guidelines inform the prevention and management of ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and trauma. The use of pharmacological and electrical stimulation in cases of vegetative (UWS) and minimally conscious states remains controversial.
- Cardiac arrest
- Hypertensive encephalopathy
- Basilar artery thrombosis
- Cerebral venous thrombosis
- Alcohol-use disorder
- Substance abuse and overdose
- Carbon monoxide poisoning
- Sepsis-associated encephalopathy
- Bacterial meningitis
- Seizure disorder
- Traumatic brain injury
- Hepatic encephalopathy
- Wernicke encephalopathy
- Subarachnoid hemorrhage
- Brain abscess
- Brain tumor
- Mitochondrial disorder
- Thyroid storm
- Psychogenic unresponsiveness
- Locked-in state
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