Файл: PLUM AND POSNER S DIAGNOSIS OF STUPOR AND COM-1.pdf

ALTERED STATES OF CONSCIOUSNESS

DEFINITIONS

Consciousness

Acutely Altered States of Consciousness Subacute or Chronic Alterations of

Consciousness

APPROACH TO THE DIAGNOSIS OF THE COMATOSE PATIENT

PHYSIOLOGY AND PATHOPHYSIOLOGY OF CONSCIOUSNESS AND COMA

The Ascending Arousal System Behavioral State Switching Relationship of Coma to Sleep

The Cerebral Hemispheres and Conscious Behavior

Structural Lesions That Cause Altered Consciousness in Humans

ALTERED STATES OF

CONSCIOUSNESS

And men should know that from nothing else but from the brain came joys, delights, laughter and jests, and sorrows, griefs, despondency and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear and know what are foul, and what are fair, what sweet and what unsavory . . .

—The Hippocratic Writings

Impaired consciousness is among the most difficult and dramatic of clinical problems. The ancient Greeks knew that normal consciousness depends on an intact brain, and that impaired consciousness signifies brain failure. The brain tolerates only limited physical or metabolic injury, so that impaired consciousness is often a sign of impending irreparable damage to the brain. Stupor and coma imply advanced brain failure, just as, for example, uremia means renal failure, and the longer such brain failure lasts,

the narrower the margin between recovery and the development of permanent neurologic injury. The limited time for action and the multiplicity of potential causes of brain failure challenge the physician and frighten both the physician and the family; only the patient escapes anxiety.

Many conditions cause coma. Table 1–1 lists some of the common and often perplexing causes of unconsciousness that the physician may encounter in the emergency department of a general hospital. The purpose of this mono-

graph is to describe a systematic approach to the diagnosis of the patient with reduced consciousness, stupor, or coma based on anatomic and physiologic principles. Accordingly, this book divides the causes of unconsciousness into two major categories: structural and metabolic. Chapter 1 provides background information on the pathophysiology of impaired consciousness, as well as the signs and symptoms that accompany it. In Chapter 2 this information is used to define a brief but informative neurologic examination that is necessary to

determine if the reduced consciousness has a structural cause (and therefore may require immediate imaging and perhaps surgical treatment) or a metabolic cause (in which case the diagnostic approach can be more lengthy and extensive). Chapters 3 and 4 discuss pathophysiology and specific causes of structural injury to the brain that result in defects of consciousness. Chapter 5 examines the broad range of metabolic causes of unconsciousness, and the specific treatments they require. Chapter 6 explores psychiatric causes of unresponsiveness, which must be differentiated from organic causes of stupor and coma. Chapter 7 provides a systematic discussion of the treatment of both structural and metabolic coma. Chapter 8 explores the outcomes of coma of different causes, including the prognosis for useful recovery and the states of long-term impairment of consciousness. Chapter 9 reviews some ethical problems encountered in treating unconscious individuals.

DEFINITIONS

Consciousness

Consciousness is the state of full awareness of the self and one’s relationship to the environment. Clinically, the level of consciousness of a patient is defined operationally at the bedside by the responses of the patient to the examiner. It is clear from this definition that it is possible for a patient to be conscious yet not responsive to the examiner, for example, if the patient lacks sensory inputs, is paralyzed (see lockedin syndrome, page 7), or for psychologic reasons decides not to respond. Thus, the determination of the state of consciousness can be a technically challenging exercise. In the definitions that follow, we assume that the patient is not unresponsive due to sensory or motor impairment or psychiatric disease.

Consciousness has two major components: content and arousal. The content of consciousness represents the sum of all functions mediated at a cerebral cortical level, including both cognitive and affective responses. These functions are subserved by unique networks of cortical neurons, and it is possible for a lesion that is strategically placed to disrupt one of the networks, causing a fractional loss of conscious-

ness.1 Such patients may have preserved awareness of most stimuli, but having suffered the loss of a critical population of neurons (e.g., for recognizing language symbol content, differences between colors or faces, or the presence of the left side of space), the patient literally becomes unconscious of that class of stimuli. Patients with these deficits are often characterized as ‘‘confused’’ by inexperienced examiners, because they do not respond as expected to behavioral stimuli. More experienced clinicians recognize the focal cognitive deficits and that the alteration of consciousness is confined to one class of stimuli. Occasionally, patients with right parietotemporal lesions may be sufficiently inattentive as to appear to be globally confused, but they are not sleepy and are, in fact, usually agitated.2

Thus, unless the damage to cortical networks is diffuse or very widespread, the level of consciousness is not reduced. For example, patients with advanced Alzheimer’s disease may lose memory and other cognitive functions, but remain awake and alert until the damage is so extensive and severe that response to stimuli is reduced as well (see vegetative state, page 8). Hence, a reduced level of consciousness is not due to focal impairments of cognitive function, but rather to a global reduction in the level of behavioral responsiveness. In addition to being caused by widespread cortical impairment, a reduced level of consciousness can result from injury to a specific set of brainstem and diencephalic pathways that regulate the overall level of cortical function, and hence consciousness (Figure 1–1). The normal activity of this arousal system is linked behaviorally to the appearance of wakefulness. It should be apparent that cognition is not possible without a reasonable degree of arousal.

Sleep is a recurrent, physiologic, but not pathologic, form of reduced consciousness in which the responsiveness of brain systems responsible for cognitive function is globally reduced, so that the brain does not respond readily to environmental stimuli. Pathologic alteration of the relationships between the brain systems that are responsible for wakefulness and sleep can impair consciousness. The systems subserving normal sleep and wakefulness are reviewed later in this chapter. A key difference between sleep and coma is that sleep is intrinsically reversible: sufficient stimulation will return the individual to a normal waking state. In contrast, if patients

with pathologic alterations of consciousness can be awakened at all, they rapidly fall back into a sleep-like state when stimulation ceases.

Patients who have a sleep-like appearance and remain behaviorally unresponsive to all external stimuli are unconscious by any definition. However, continuous sleep-like coma as a result of brain injury rarely lasts more than 2 to 4 weeks.

Acutely Altered States

of Consciousness

Clouding of consciousness is a term applied to minimally reduced wakefulness or awareness, which may include hyperexcitability and irritability alternating with drowsiness. A key distinction must be made in such patients between those who are confused (i.e., do not respond appropriately to their environment) because of a focal deficit of cognitive function versus those who have more global impairment. The beclouded patient is usually incompletely oriented to time and sometimes to place. Such patients are inattentive and perform poorly on repeating numbers backward (the normal range is at least four or five) and remembering details or even the meaning of stories. Drowsiness is often prominent during the day, but agitation may predominate at night.

The pathophysiology of brain function in such patients has rarely been studied, but Posner and Plum3 found that cerebral oxygen consumption had declined by 20% below normal levels in patients with hepatic encephalopathy with lethargy and global confusion, and Shimojyo and colleagues noted similar reductions in patients with lethargy and global confusion due to Wernicke’s encephalopathy.4 More recently, Trzepacz and colleagues have identified decreased regional cerebral blood flow (CBF) bilaterally in the frontotemporal cortex and right basal ganglia of patients with subclinical hepatic encephalopathy.5 Increases in CBF during treatment of cobalamin deficiency correlate with clinical improvement.6 Other studies have implicated reduced cholinergic function; excess release of dopamine, norepinephrine, and glutamate; and both decreased and increased serotonergic and gamma-aminobutyric acid (GABA) activity.7 The pathogenesis of clouding of consciousness and delirium is discussed in more detail in Chapter 5.

Delirium, from the Latin ‘‘to go out of the furrow,’’ is a more floridly abnormal mental state characterized by misperception of sensory stimuli and, often, vivid hallucinations. Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV),8 as follows: ‘‘A. Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention. B. A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance that is not better accounted for by a pre-existing, established or evolving dementia. C. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day.’’

Delirious patients are disoriented, first to time, next to place, and then to persons in their environment. Rarely are patients unaware of who they are, although sometimes married women will revert to their maiden name. Patients are often fearful or irritable and may overreact or misinterpret normal activities of physicians and nurses. Delusions or hallucinations may place the patient completely out of contact with the environment and the examiner. Full-blown delirious states tend to come on rapidly and rarely last more than 4 to 7 days. However, fragments of misperceptions may persist for several weeks, especially among alcoholics and patients with cerebral involvement from collagen vascular diseases.

Delirium with agitation occasionally may be seen as a consequence of focal lesions of the right parieto-occipitotemporal cortex,2,9 but generally is indicative of bilateral impairment of cortical function in toxic-metabolic states, such as atropine poisoning, alcohol or sedative drug (e.g., benzodiazepine) withdrawal, acute porphyria, or hepatic or renal failure. It also occurs with systemic infectious processes or as a component of encephalitis, during which immune mediators such as cytokines and eicosanoid derivatives may cloud mental function.

Obtundation, from the Latin ‘‘to beat against or blunt,’’ literally means mental blunting or torpidity. In a medical setting, such patients have a mild to moderate reduction in alertness, accompanied by a lesser interest in the environment. Such patients have slower psychologic responses to stimulation. They may have an