Disorders of Consciousness in Systemic Diseases

Historical Perspective

Ever since the Greek physician Galen (130 to 200 a.d. ) recognized that a wound of the brain could affect the mind, the roles of consciousness and thought as manifestations of brain injury and impairment have held a special role. During the Renaissance, the philosopher Descartes (1596 to 1650) focused on the “mind–brain problem.” He thought that the pineal gland was the seat of the soul, and this structure therefore played a special role in his concept of consciousness, although contemporaries granted this honor to the corpus callosum. Late nineteenth and early twentieth century efforts such as William James’s “stream of consciousness” focused on psychologic, not anatomic, mechanisms. Although the effect of systemic diseases on consciousness has been recognized since Hippocrates in the fifth century b.c. described “madness on account of bile,” the ability to ascribe testable anatomic and biologic correlates to consciousness is distinctly modern. The two main advances that have made this possible are (1) development of an operational definition of consciousness that has practical applicability and (2) understanding of the anatomic substrate of consciousness.

Definition of Consciousness

In medicine, consciousness can be defined as awareness of self and the environment. Thus, decreased consciousness involves impairment of this state of awareness, with coma being its absence. Consciousness and conscious behavior have two basic components: arousal and content. Arousal is behaviorally related to the level of alertness or wakefulness. Content describes the complex range of cognitive functions, including thought, memory, and language. As described later, a simplified anatomic model of consciousness gives arousal and content distinct anatomic localizations. Arousal and content may be independent but are frequently interdependent. For content to be present or at least to be assessed clinically, some degree of arousal must be present. Conversely, if decreased arousal (e.g., from sedative drug intoxication) is overcome by a noxious stimulus, content may be seen to be largely normal until arousal fades again. A description of the state of consciousness of an individual must take into account both level of arousal and quality of content. Different diseases and neuroanatomic sites may be implicated, depending on the specifics of the state of consciousness. The term level of consciousness usually refers to level of arousal ( Table 61-1 ).

Anatomy of Consciousness

Although somewhat of an oversimplification, the two different components of consciousness are mediated by two distinct neuroanatomic systems ( Fig. 61-1 ). Arousal is mediated by the ascending reticular activating system (RAS). The RAS is located in the brainstem and is a loosely arranged column of neurons extending from the upper third of the pons to the diencephalic structures of the thalamus and hypothalamus. Projections via subcortical relay nuclei, primarily in the thalamus, integrate RAS-mediated arousal with more diffuse cerebral cortical functions. Experimental studies have demonstrated that stimulation of the RAS in a sleeping animal results in immediate behavioral arousal, but when the RAS is destroyed, no amount of sensory stimulation reverses coma, even with subcortical and cortical structures intact.

The content of consciousness is localized more broadly throughout the cerebral cortex. Certain cognitive functions are diffusely localized throughout both cerebral hemispheres, whereas other functions may have more narrow localization. Receptive language and expressive language are principally localized to the superior temporal lobe or posterior frontal lobe, respectively, of the dominant hemisphere. Although various aspects of memory may be stored diffusely, the mesial temporal lobes and mammillary bodies are important for storage of new short-term memory. Conversely, processes such as thought, orientation, attention, and planning are localized diffusely, especially among both frontal lobes. Because a severe impairment of receptive language is likely to alter the state of awareness of self or environment (as far as can be deduced by examination), some may consider it an altered state of consciousness. Others place more emphasis on impairment of bihemispheric dysfunction, evidenced by decreased attention, concentration, and coherent thought, as defining altered content of consciousness. The important lesson is that different aspects of the content of consciousness may have different anatomic localizations and that global impairment of cognitive function implies bilateral cerebral hemispheric dysfunction or disease.

Implications for Systemic Diseases

Coma, or unconsciousness, is a state of unresponsiveness in which the subject has closed eyes and cannot be aroused appropriately with stimuli. For coma to be present, one of two general anatomic conditions must be satisfied: there must be significant impairment of either the RAS or both cerebral hemispheres ( Table 61-2 ). Structural lesions usually cause coma through direct brainstem involvement or through brainstem displacement or compression with subsequent RAS involvement. The underlying pathologic processes are often primary neurologic disorders such as intracerebral hemorrhage, traumatic brain injury, subdural hematoma, brain tumors or abscesses, or large cerebral infarctions with mass effect. Transtentorial herniation because of a supratentorial mass, direct brainstem impingement from an infratentorial lesion, or direct parenchymal brainstem involvement from hemorrhagic or ischemic stroke are common examples. Less commonly, subfalcine herniation or bihemispheric mass lesions may lead to coma with an intact brainstem due to diencephalic injury. Metabolic disturbances, by contrast, usually cause coma from diffuse bihemispheric involvement, which presumably results in disconnection between the RAS (and subcortical thalamic relay nuclei) and the hemispheres. The neurologic examination of the comatose patient is an important key in distinguishing the cause and anatomic basis of coma, specifically the presence or absence of brainstem and cranial nerve abnormalities such as pupillary or extraocular movement dysfunction. The cause of lesser degrees of impaired level of consciousness can also be assessed by determining whether bihemispheric or brainstem dysfunction is responsible.

Sleep should be considered as a separate and distinct entity. Externally, patients in coma initially appear asleep, but sleeping individuals can be roused and then respond to the environment. Normal sleep has several stages that have distinct electroencephalographic (EEG) patterns as discussed in Chapter 51. The EEG findings in coma may vary, depending on the cause, but, in general, do not resemble those of sleep. Altered consciousness in systemic disease is a pathologic state in contrast to sleep, which is a necessary and normal function.