Chapter 17 - Depression of consciousness
We should begin with some definitions because medical and lay jargon for the various levels of depression of consciousness are not consistently applied. Careful observation of the subject's behavior (or absence of behavior) is most informative.
Coma is a pathologic state of unconsciousness from which a person cannot be aroused to make any purposeful responses. As a rule light coma is present when reflex motor response (i.e., decorticate and decerebrate posturing) can be elicited by noxious stimulation. In deep coma there is no response.
Stupor is a state of pathologic reduced consciousness from which the patient can be aroused to purposeful response only with intense or persistent stimulation. This includes the broad range from persistent drowsiness (from which the patient can be briefly aroused to produce purposeful responses by stimulation) to deep stupor, from which the patient can only be aroused to produce poorly directed defense against intense, noxious stimuli.
Sleep, by contrast, is a nonpathologic depression of consciousness from which the subject can be aroused to persistent alert wakefulness with appropriate non-noxious stimuli. Sleep is an active and reversible state of consciousness.
Hysterical coma or stupor is feigned or subconsciously assumed depression of consciousness. This is differentiated clinically from true coma or stupor by a normal and alert electroencephalogram, the presence of nystagmus on caloric irrigation of the external auditory canal (see Chapter 6), and the absence of abnormal neurologic signs.
There are some neurologic conditions in which a person has lost most if not all ability to move without impairment of consciousness. For example, blockade or damage of neuromuscular junction (as with severe myasthenia gravis or certain drugs and medications) and conditions that diffusely affect peripheral nerves (such as Guillain-Barre syndrome or porphyria) can prevent a patient from responding, although s/he may be perfectly awake and alert (though on a ventilator). However, these patients are not likely to be considered comatose since the history is usually obvious.
On the other hand, there are conditions that damage the base of the pons that may not be so obvious. When the base of the pons is severely damaged, usually by hemorrhage, infarction or acute destruction of myelin (such as by central pontine myelinolysis), the patient becomes acutely unresponsive (despite being awake and aware). Such patients are unable to move except for vertical and convergent eye movement and eye-opening systems (these functions are located in the midbrain). The auditory system, lying laterally along the brain stem, usually is not affected by the damage which often arises from involvement of the paramedian arteries. Thus the patient hears and sees. Unless the clinician asks them to look up or down, the patient may be thought to be comatose. They are said to be "locked in", a term aptly applied to this state by Plum and Posner.
Hysterical coma or stupor is feigned or subconsciously assumed depression of consciousness differentiated clinically from true coma or stupor by a normal and alert electroencephalogram, the presence of nystagmus on caloric irrigation of the external auditory canal (see Chapter 6) and the absence of abnormal neurologic signs.
Table 17-1 lists examples of the more common processes leading to pathologic depression of consciousness.
Substrates of consciousness
Before considering the conditions affecting consciousness, it is worth considering the brain structures that are necessary to maintaining it. Consciousness requires varying amounts of normal activity of the cerebral cortex since the hemispheres are the substrate for awareness of self and environment and embody the sentient functions that define human intellectual existence. Therefore, anything that diffusely depresses the activity of cerebral cortical neurons will produce stupor and coma. In general, this can either be due to actual destruction of cortical neurons or can be due to conditions that suppress the activity of the cortex, which is generically called "encephalopathy". It is important to note that normal activity of the cerebral cortex is maintained by activity in the reticular formation of the rostral brain stem extending from the rostral pons and caudal midbrain through the diencephalon (Figure 17-1), termed the reticular activating system.
The reticular formation can function normally even after destruction of the cerebral cortex (such as following diffuse cerebral anoxia from cardiac arrest). In general, the cerebral cortex is more sensitive to metabolic or toxic damage. In the case of the patient with diffuse cerebral cortical damage, the reticular formation and brain stem may be capable of supporting a crude sleep-waking vegetative state. In contrast, the cerebral hemispheres cannot function in the absence of reticular activation. Bilateral loss of the reticular formation at the midbrain level (for example from severe ischemic or hemorrhagic damage of the upper brain stem), is likely to terminate all meaningful cerebral activity.
In this chapter we concern ourselves with the two processes that depress consciousness, those being by diffuse suppression of cerebral cortical activity or by damaging the reticular formation. Some conditions do both. We will consider these two potential substrates for stupor and coma and how they are approach and evaluated.
Stupor and coma that is due to diffuse depression of cerebral cortical function is almost invariably the result of metabolic abnormality or toxic effect on the cortex and is termed "encephalopathy". Depending on the type and degree of metabolic insult, the reticular formation may also be depressed. However, the reticular formation is substantially more resistant to metabolic and toxic influences than the cerebral cortex, so brain stem functions are relatively preserved.
In general, metabolic depression of brain function (encephalopathy) is the most common cause of stupor and coma and may manifest itself in a number of ways. The various manifestations of metabolic encephalopathy are discussed in greater detail in these case examples. Table 17-1 lists the basic categories of metabolic dysfunction associated with depression of consciousness that must be considered.
As described above, the midbrain reticular formation (reticular activating system) is necessary for maintenance of consciousness. The reticular formation can be suppressed by the same processes that suppress cerebral cortical function, although the reticular formation is somewhat more resistant than the cortex. However, the reticular formation is also susceptible to direct damage because of the fact that it is contained in a relatively small area of the brain stem. Several types of lesions commonly directly damage the reticular formation, the most common being ischemia/infarction, hemorrhage, neoplasm, abscess, or direct trauma. In addition to these primary injuries, the reticular formation can also be damaged by compression. This usually results from a space-occupying lesion that forces part of the temporal lobe (usually the uncus) through the tentorial notch. Recall that the midbrain passes through this notch. This process, termed "transtentorial herniation" (or "uncal herniation") occurs due to space occupying lesions that affect the hemispheres. These include neoplasms/tumors, hemorrhage (intracerebral, subdural, or epidural hematomas), abscesses, or conditions causing brain edema.
In the case of herniation, the initial lesion is usually unilateral and many cases present with signs and symptoms of damage to that side of the brain (e.g., contralateral hemiparesis, hemihypoesthesia, dysphasia) that precede secondary brain stem compression. As the pressure builds, the medial temporal lobes shift away from the lesion compressing the midbrain reticular formation (fig. 17-2). This results in the depression of consciousness. As can be seen in the figure, brain stem compression occurs because the vectors of force from an expanding mass in the hemispheres are directed toward the tentorial notch, which is the only significant exit from the otherwise closed, rigid-walled, supratentorial space. This progression of transtentorial herniation results in what has been termed “rostrocaudal deterioration” in function. Progressively, the diencephalon, mesencephalon, and finally the pons and medulla are compromised. Remember, the expanding mass that causes this can be anything that occupies space, including swollen (edematous) brain tissue.
From the above discussion, you should be aware that depressed consciousness might result from either bilateral cerebral cortical depression (often with later suppression of reticular function) or from damage to the brain stem reticular activating system. The neurologic exam of the comatose patient is primarily focussed on discriminating these two types of causes of depressed consciousness. This is because the conditions that produce diffuse cortical suppression are very different from the conditions that damage the reticular activating system and require totally different further evaluation and management. Therefore, once the immediately life-threatening issues are being brought under control (hemorrhage, respiratory, or cardiovascular arrest) the evaluation of the comatose patient focuses on beginning the evaluation to differentiate these two broad types of coma. This permits the immediate and correct selection of further diagnostic tests and institution of appropriate therapeutic management. Table 17-2 lists the major steps taken by the physician from the time the patient enters the emergency department.
The neurologic evaluation of the comatose patient can be a relatively rapid and efficient procedure and should enable the examiner to differentiate between bilateral cerebral cortical depression (encephalopathy) versus damage to the brain stem reticular formation. Of course, it is not possible to examine all elements of the nervous system in the patient with depressed consciousness. However, careful observation of five categories of neurologic function is adequate for these purposes in most cases: (1) level of consciousness, (2) respiratory rate and pattern, (3) pupillary function, (4) oculomotor-vestibular function, and (5) motor function. The evaluation of these levels of functioning can help to differentiate encephalopathy from brain stem damage. Also, serial observation of these variables can detect progression of the condition. An excellent 12 minute video on this part of the exam can be found here.
The degree of impairment of consciousness is assessed, ranging from awake and alert to stuporous and comatose based on the degree of response to stimulation. Of course, the patient who is awake and alert responds appropriately and normally to questions and commands. The patient who is drowsy opens their eyes to verbal stimulation and responds appropriately, but drifts back to a condition with their eyes closed when not stimulated. A deeper stupor requires more vigorous stimulation in order to get the patient to open their eyes and attend to stimuli. And finally, in a deep coma, there is no response to even noxious stimulation (such as tickling the nostrils or squeezing the fingernail). Motor responses range from being able to follow commands, through localization of noxious stimuli, to simple withdrawal from noxious stimuli to decorticate posturing and decerebrate posturing as progressively lower parts of the nervous system are involved. Note that the patient showing a best motor response of withdrawal or posturing would not be conscious. This level of motor response should be recorded so that it can be determined whether the patient is deteriorating as time passes.
2. Respiration (see Figure 1-1).
The inspiratory and expiratory centers are located in the medullary reticular formation. These areas are under control from higher levels of the neuraxis and different patterns of respiration will occur as progressive levels of the nervous system are suppressed or damaged. These respiratory patterns have a general, although not perfectly reliable, relationship to involvement of different levels of the brain stem.
- a. Diffuse cerebral cortical dysfunction is often accompanied by drowsiness with sighing respirations and yawning.
- b. When the diencephalon or upper mesencephalon is suppressed or damaged, Cheyne-Stokes respiratory pattern is often seen (this is a crescendo-decrescendo pattern of respirations which is punctuated by periods of apnea of variable length). This type of respiration may also be seen with diffuse bilateral cerebral involvement as well and may be most prominent when the patient is sleeping (i.e., presumably when further cerebral depressing mechanisms are in effect). It is also seen during sleep in some normal individuals.
- c. Damage to the lower mesencephalon or upper pons produces central neurogenic hyperventilation (rapid [20-40 per minute], deep breathing, usually significant enough to cause respiratory alkalosis if no pulmonary compromise is present.
- d. Damage to the lower pons produces a change to ataxic respirations (irregularly irregular breathing) that have inconstantly varying rhythm and rate. There may also be central neurogenic hyperventilation or apneustic breaths (which consist of a long arrest of breathing at the end of inspiration, resembling breath holding).
- e. When the medulla is significantly involved, there is depression and finally cessation of respiration (apnea).
Obviously, the changes between these types of respirations can attend changes in the patient's condition and progression down the list (from Cheyne-Stokes to central neurogenic hyperventilation, for example) is a sign of a worsening state.
Pupil size and reactivity are mediated through variations in the equilibrium between sympathetic dilation and parasympathetic constriction (see Chapter 4).
- Isolated damage or suppression of the cerebral cortex will not change the pupil or its reflexes.
- If the diencephalon is severely damaged the pupils are constricted due to inhibition of the hypothalamic centers that activate sympathetic pupillary dilator function. However, these pupils will still react to light.
- As more caudal levels of the diencephalon and rostral mesencephalon begin to be involved, the pretectal nuclei may be compromised, causing a sluggishness of pupillary reactivity even though pupils are still small.
- Damage to the mesencephalon often affects the oculomotor complex or the third nerve. This will cause the pupils to be widely dilated (7-9 mm) because of loss of parasympathetic function. These pupils do not react to light.
- Damage to more caudal levels of the midbrain will damage the sympathetics as well, resulting in a pupil that is midposition in size (4-7 mm, varying from individual to individual) and unreactive to light.
- If the brain stem down through the pons-medulla is involved, the pupils continue to be midposition and fixed.
- There are a couple of special cases. If the pons or medulla is selectively damaged (with preservation of midbrain function) the pupils will be small and reactive because only the descending sympathetic pathways are damaged (with preserved parasympathetic/oculomotor nerve). This is most commonly seen in pontine hemorrhage. In these cases, the pupils are frequently 1mm or smaller and, because the pupils are so small, it may be impossible to see that they still react (a bright light and magnifying glass reveals a tiny amount of reaction). A similar situation occurs with narcotic overdose, where the pupils may be maximally constricted (pinpoint, 0.5 mm or less) and therefore appear unreactive to light.
- Suppression of brain stem function (such as by drugs, toxins or metabolic upsets) can abolish the pupillary light reflex. However, the pupillary light reflex is usually the last brain stem function to be suppressed due to drugs or metabolic insults (encephalopathy). It may require a very strong light and a magnifying lens (such as on an otoscope) to see the constriction, however.
4. Oculomotor-vestibular function (see Chapter 6).
Vestibulo-ocular function is one of the most important evaluations that can be made in the comatose patient. This is because the reflexes involved in eye movements to vestibular stimulation traverse most of the core of the brain stem (adjacent to the reticular activating system). Additionally, in the patient who is awake and alert, there are competing reflexes generated by the cerebral cortex that produce a distinctive pattern of eye movements called nystagmus. This video shows a normal response to infusion of ice water into the left ear canal in an awake and alert subject. If this person had an intact brain stem reticular activating system but was in a coma due to suppression of the cerebral cortex, the eyes would have drifted toward the side of the ice water and stayed there for minutes after the infusion, but would not have had the jerks of nystagmus. Therefore, this single assessment can determine whether the brain stem reticular formation is intact and also how alert the cerebral cortex is.
- Diffuse suppression or damage of the cerebral cortex results in loss of the fast component of the vestibulo-ocular reflex (i.e., the nystagmus). The degree of suppression of this fast component is proportional to the degree of loss of cortical function. Tonic conjugate horizontal deviation of the eyes during caloric or oculocepahlic testing indicates preserved brain stem reflex activity (and, by extension, intact reticular activating system) with loss of cortical input.
- Brain stem damage to the midbrain often produces dysconjugate movement of the eyes.
- With brain stem damage through the lower pons there is loss of all response to caloric and oculocephalic stimulation because the paramedian reticular formation subserving conjugate horizontal gaze and the sixth-nerve nuclei are affected. At this stage there will be no corneal reflex.
5. Motor function (see Chapter 8).
- Noxious stimulation produces a number of levels of response in the stuporous or comatose patient. The lightly stuporous patient will localize a noxious stimulus, knocking your hand away or grabbing it, for example. A slightly less responsive patient will withdraw the body part that is being stimulated. This withdrawal will be stereotyped.
- In a comatose patient in whom the diencephalon is being damaged or suppressed, noxious stimulation will produce decorticate posturing (also see fig. 10-1). Decorticate posturing includes stereotyped flexion of the arm, wrist and fingers, with extension of the lower limbs. This posturing may be asymmetrical initially (appearing first on the side with greater damage).
- If the process progresses to affect the mesencephalon or upper pons, decerebrate posturing begins to appear following noxious stimulation. This consists of extension and internal rotation of the arms and legs (see see fig. 10-1).
- If the damage also involves the lower pons and medulla, the response to noxious stimuli is usually eliminated. Acute lesions of this region almost invariably results in flaccid quadriplegia. This loss of function is seen to a greater extent and lasts longer the farther down the neuraxis that the acute damage occurs. Later on (if the patient survives such an acute lesion) spastic tendon reflexes may appear, along with primitive spinal withdrawal reflexes (such as the Babinski response).
Expanding masses are a model for discussion of the effects of damage to the various levels of the nervous system. Masses can include tumors, abscesses or hemorrhage but also can include edema. Expanding masses result in a somewhat predictable rostral-caudal deterioration of neural function which is likely to be fatal unless the process can be stopped. In these patients, cortical function is affected first (usually with some lateralizing signs), followed by dysfunction of the diencephalon, then midbrain. This is often accompanied by herniation of the uncus of the medial temporal lobe, called uncal herniation or transtentorial herniation. Later the pons and medulla are likely to be affected. Figure 17-2 depicts an expanding right intracerebral hemorrhage and its effect on the rostral brain stem. The sequential effects of such a lesion on functions in the 5 categories (consciousness, respirations, pupils, oculomotor/vestibular function and motor response) are listed in Table 17-3.
The first effect of such an expanding lesion would be due to its local effects on sensory and motor function (for example, in the figure 17-2 of a patient with a mass lesion on the right side, there may be left hemiparesis, loss of sensation on the left or a left visual field deficit). However, when the mass expands to the level of pressing on the upper brain stem (i.e., diencephalon), characteristic changes in the 5 variables (i.e., consciousness, respiration, pupils, vestibulo-ocular function and motor response) will begin to occur. The deterioration of these variables usually follows a predictable sequence, although steps can be skipped, particularly in rapidly evolving lesions. For example, consciousness will progress from stupor to coma; respirations will progress from eupnea through Cheyne-Stokes respirations, central neurogenic hyperventilation, ataxic breathing and, finally apnea; pupils will progress from normal reactive, through small reactive, to midposition/fixed; the vestibulo-ocular response will go from normal nystagmus through loss of the fast component, to dyconjugate response and then loss of the tonic phase of the reflex (usually accompanied by loss of the corneal reflex); and the motor response will deteriorate from normal mobility, to localizing noxious stimuli, to withdrawal responses, then decorticate posturing and decerebrate responses before losing all motor response other than simple spinal reflexes. The chart usually allows you to determine the level of preserved function (Table 17-3).
It is a useful exercise to understand these levels of function. However, for practical purposes, the determination of progressive levels of rostrocaudal deterioration has prognostic but little therapeutic value once the process has extended beyond the midbrain. In acute compressive injuries, severe loss of midbrain function is often accompanied by secondary hemorrhages (Duret hemorrhages) in the core of the midbrain and pons. This is associated with permanent cessation of reticular activating system function (i.e., irreversible coma). These hemorrhages are presumed to occur due to tearing of the tiny penetrating blood vessels. Because of the irreversibility of the condition once it has progressed, it is extremely important to recognize rostrocaudal deterioration and institute therapy early in order to prevent progression.
The most common causes of stupor and coma fall into the category of toxic/metabolic encephalopathy (this includes sedative drug-related stupor and coma). The cerebral cortex is very susceptible to toxic, metabolic or drug-related suppression of activity, much more susceptible is the brain stem. Therefore, toxic and metabolic causes of coma initially spare brain stem reflexes such as the vestibular, respiratory and pupillary responses. The pupillary light reflex is usually the last reflex to be detected as the brain stem is being suppressed by the toxic, metabolic or drug related insult. A very bright light may be necessary to detect the pupillary response.
Once the assessment has been made that the patient has a toxic/metabolic or drug-related encephalopathy, you must consider the large array of potential causes. many of the most common are included under #2 in Table 17-1. Please see this web page for some supplemental specific case exercises illustrating the principles of evaluation and management of patients with depression of consciousness.
Dementia vs. encephalopathy
We have already discussed dementia (Chapter 2 and Chapter 16), which results from bilateral degeneration of the cerebral hemispheres. Of course, dementia causes varying degrees of loss of cognitive and emotional function. However, if dementia is very severe, there may be so much loss of cortical function as to produce depressed consciousness. However, more often, depressed consciousness in a patient with dementia is due to the presence of one or more metabolic dysfunctions. Patients with dementia are very susceptible to conditions (and drugs) that depress remaining cortical function. Conditions that usually don’t result in major change in consciousness in healthy individuals (such as mild to moderate infections, renal insufficiency, simple dehydration or malnutrition, or mild sedative drugs), may result in coma in a patient with dementia (such as Alzheimer’s disease).
- Plum, F., Posner, J.B.: Diagnosis of Stupor and Coma, ed. 3. Philadelphia, F.A. Davis Co., 1980.
Define the following terms:stupor, coma, delerium, encephalopathy, reticular activating system, decorticate posture, decerebrate posture, "locked-in", Cheyne-Stokes respirations, central neurogenic hyperventilation, ataxic respiration, vestibulo-ocular reflex, diencephalic pupils.
17-1. What are the two potential causes of coma?
17-2. What are the causes of diffuse cerebral cortical suppression?
17-3. What physical findings would indicate that coma was due to diffuse cerebral cortical dysfunction rather that to brain stem damage?
17-4. What are key physical exam findings in patients with coma?
17-5. What is transtentorial herniation?
17-6. What are common symptoms of transtentorial herniation?
17-7. What is the "locked-in" syndrome?
17-8. How can you recognize "locked-in" syndrome?