Consciousness, coma, and the vegetative state: physical basis and definitional character.

• Author: De Giorgio, Christopher M.

Coma is a common event. In the United States alone, there are more than one thousand persons daily who sustain a cardiac arrest. (1) Eighty percent of those successfully resuscitated are comatose at one hour. (2) Yet cardiac arrest is only the third leading cause of coma; drug overdose and head trauma are even more common. (3) Once a patient has become comatose, the etiology of the coma, as well as the depth and the duration of coma, become the leading predictors of outcome. For example, in coma secondary to cardiac arrest, anoxic coma, the mortality is nearly 90%. (4) In the setting of head trauma, the mortality approaches 50%. (5) Yet the mortality from drug overdose may be as low as 1-5%. (6) Since etiology, depth, and duration are so critical, physicians must rapidly assess patients in coma, correctly determine the cause, and initiate specific therapy as soon as possible. Afterwards, the treating physician may request a neurologic consultation to determine prognosis based on the clinical examination, neuro-imaging, and neurophysiologic studies.

The Physiologic and Anatomic Basis for Consciousness

Consciousness is contingent on a functionally intact brainstem and cerebral cortex. (7) The alteration of consciousness has long been attributed to either bilateral injury to the cerebral cortex or lesions of the brainstem. The region in the brainstem critical to maintaining consciousness is the ascending reticular activating system (ARAS). (8) The principal anatomic substrate of the ARAS is the reticular formation, a mesh of large and medium sized neurons located in the tegmentum (or middle) of the brainstem, extending from the medulla (lowest portion of the brainstem) through the pons (the middle of the brainstem) to the midbrain (highest) region of the brainstem). (9) The reticular formation regulates wakefulness and sleep, postural and muscle reflexes, pain, and autonomic function governing cardiovascular and respiratory centers. (10) Fibers from the reticular formation synapse with the thalamus, limbic system, and cerebral cortex. (11) Sensory fibers relaying touch, pain, movement, sound, and other modalities in turn synapse with reticular formation neurons. (12) Thus the reticular formation serves not only to integrate sensory stimuli but also either to arouse or inhibit higher structures, i.e., the thalamus and cerebral cortex. (13)

The function of the ARAS was elicited via a series of ablative experiments that led investigators to believe that specific centers for consciousness, arousal, and sleep existed. (14) For example, transection of the cat brainstem at the mid-pontine level produced a cat with an arousal pattern on the EEG. More rostral (anterior) lesions in the midbrain produced behavioural stupor. As such, this would suggest that specific neural populations in the brainstem are responsible for wakefulness and sleep.

The principal means of communication in the brain is via chemicals secreted by neurons called neurotransmitters. Serotonin and norepinephrine are two such neurotransmitters. Norepinephrine is produced in the locus ceruleus beneath the floor of the fourth ventricle in the pons. (15) Fibers from the locus ceruleus are widely distributed to the thalamus, cortex, cerebellum, and spinal cord. Norepinephrine release is associated with an alerting, attentive state probably due to a diminished threshold of the neurons of the ARAS. (16) The raphe nuclei--a midbrain structure--have been shown to produce serotonin, which regulates sleep, and substance P, which modulates the sensation of pain. (17)

Lesion of the brainstem ARAS usually result in coma. (18) However, even large lesions in the brainstem, if strategically placed, may not affect consciousness, so long as the reticular formation is intact. (19) A special case of pseudo-coma is a syndrome in which the patient appears to be comatose but is actually awake, (20) termed the "locked-in" syndrome by Plum and Posner. (21) Affected individuals are severely quadriplegic but retain vertical eye movement as well as eyelid control and may be able to communicate in this way. (22) Consciousness is thus preserved. This "de-afferented" state usually occurs following occlusion of the basilar artery and subsequent infarction of the brainstem sparing the ARAS. (23) Other causes of locked-in syndrome include head and neck trauma, tumors, hemorrhage, and demyelination. (24)

Assessment of the Level of Consciousness

After initial stabilization of the patient, the neurologic examination assesses the level of consciousness and determines if the cause of the coma is a structural lesion (stroke, tumor, trauma, infection) or secondary to a toxic or metabolic cause. (25) The neurologic examination is extremely helpful but should be complemented by cerebral imaging, computerized tomographic scans (CT) or magnetic resonance imaging (MRI), and electroencephalography (EEG) or other neurophysiologic tests (evoked potentials). (26)

First, the mental status is assessed. Operationally, levels of consciousness can be defined as follows:

* DELIRIUM: Delirium is an altered state of consciousness characterized by confusion, hallucinations, and agitation, frequently alternating with lethargy. (27) Examples include alcoholic hallucinosis (DTs) with visual hallucinations (e.g., seeing little green men), drug overdose (e.g., PCP), lupus cerebritis, and herpes encephalitis. Delirium may be the first stage of progressive deterioration in mental status or may be seen during stages of recovery from coma due to anoxia.

* OBTUNDATION: Obtundation is characterized by...