Chapter 17 - Depression of consciousness
Some definitions are necessary because medical and lay jargon for the various levels of depression of consciousness is legion and loosely applied. The subject's behavior or absence of behavior as determined by careful observation and described in simple terms is most informative.
Coma is a pathologic state of unconsciousness from which a person cannot be aroused to make 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 persistent external stimulation. This covers the broad range from persistent drowsiness from which the patient can be aroused by constant stimulation for periods of alert wakefulness to deep stupor from which the patient can be aroused only to the level of poorly directed defense against noxious stimuli.
Sleep 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 suppression of reticular arousal.
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 Chap. 6) and the absence of abnormal neurologic signs.
The de-efferented state, in which a person has lost most if not all motor behavior, can occur with several conditions. Diffuse neuromuscular dysfunction as with myasthenia gravis (myasthenic crisis or overmedication with cholinesterase inhibitors) and diffuse polyradiculoneuropathy (the Guillain-Barre syndrome, porphyria) can make a patient behaviorally unresponsive, although s/he may be perfectly lucid with respiratory support. The history and presentation of these disorders are such that the patient is unlikely to be considered comatose.
When the base of the pons (less often the midbrain) is transected or the lower pons is transected in its entirety by hemorrhage or infarction, a state of deefferentation occurs that renders the patient 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 preserved tegmentum of the midbrain). The auditory system, lying laterally along the brain stem, usually is not affected by the central hemorrhage or infarction, which often arises from involvement of the paramedian vasculature. Thus the patient hears and sees. Unless the clinician asks them to look up or down, the patient may be said to be "locked in", a term aptly applied to this state by Plum and Posner. These patients' minimal ability to communicate is often unrecognized, so they are usually considered and treated as if comatose.
Table 17-1 lists examples of the more common processes leading to pathologic depression of consciousness.
Substrates of consciousness
Consciousness requires 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 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". However, this normal activity of the cerebral cortex also requires normal activity in the reticular formation of the rostral brain stem extending from the midpons through the diencephalon (Fig. 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 reticular formation and brain stem are more resistant to damage than is the cerebral cortex. In the case of the patient with diffuse cerebral cortical damage, the surviving 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 ischemic or hemorrhagic transection of the upper brain stem), will terminate all sentient cerebral activity.
In this chapter we concern ourselves with processes that depress consciousness either by diffusely suppressing cerebral cortical activity or by damaging the reticular formation (or both). We will consider these two potential substrates for stupor and coma and how we approach the evaluation of such patients.
Stupor and coma can result from depression of function of both cerebral hemispheres. This depression 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, this may also depress the function of the reticular formation. Generally, the reticular formation is substantially more resistant to metabolic and toxic influences than the cerebral cortex.
Metabolic depression of brain function 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 are suppressing cerebral cortical function. Commonly, the reticular formation is somewhat more resistant to suppression than are the more sophisticated functions of the cerebral cortex, but will be affected if the suppression is greater. However, in addition to this kind of suppression of function, 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. There are several types of lesions that damage the reticular formation. The most common of these injuries include ischemia-infarction, hemorrhage, neoplasm, abscess, or direct traumatic disruption. 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") usually occurs due to neoplasms, hemorrhage (intracerebral, subdural, or epidural hematomas), abscess, or other conditions that cause brain edema.
In the case of herniation, the initial lesion is usually unilateral and many cases present with focal lateralizing signs and symptoms (e.g., hemiparesis, hemihypoesthesia, dysphasia) that precede secondary brain stem compression (which results in the depression of consciousness). Brain stem compression occurs because the vectors of force from an expanding supratentorial mass are ultimately 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 a rostrocaudal deterioration in function. Progressively, the diencephalon, mesencephalon, and finally the pons and medulla are compromised.
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 conditions that produce diffuse cortical suppression are very different from the conditions that damage the reticular activating system. Therefore, the initial evaluation of the comatose patient focuses on differentiation of patients with these two causes of coma. This permits the immediate and correct selection of further diagnostic tests and institution of appropriate therapeutic management of the patient. 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, with little difficulty, to differentiate between the two basic causes of depression of consciousness: (1) brain stem reticular formation depression, and (2) bilateral cerebral cortical depression (with or without accompanying brain stem reticular depression). Of course, it is not possible to examine all elements of the nervous system in the patient with depressed levels of consciousness. It has been found that careful observation of five categories of neurologic function in most cases is adequate for these purposes: (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 ascertain what levels of the nervous system are and are not working and serial observation of these can detect progression of the condition.
This analysis permits determination of the degree of impairment of consciousness ranging from awake and alert to stuporous and comatose. It is based on observation of 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 nares or squeezing the fingernail). This level should be recorded so that it can be determined whether the patient is deteriorating as time passes.
2. Respiration (see Fig. 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) that have inconstantly varying rhythm and rate. With primary pontine tegmental involvement. There may also be central neurogenic hyperventilation or apneustic breaths (which consist of a long arrest of breathing at the end of inspiration and resemble breath holding).
- e. When the medulla is significantly involved, there is depression and final 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 Chap. 4).
- a. Isolated damage or suppression of the cerebral cortex will not change the pupil or its reflexes.
- b. If the diencephalon is severely damaged the pupils are constricted due to suppression of the hypothalamic origins of the sympathetic pupillodilator system. However, they will still react to light.
- c. As the caudal diencephalon and rostral mesencephalon begins to be involved, the region of the pretectal nuclei may be compromised, causing a sluggishness of pupillary reactivity when the pupil may still be small.
- d. Damage to the mesencephalon will often damage the oculomotor complex or the third nerve. This will cause the pupils to be widely dilated (7-9 mm) because of remaining sympathetic dilator tone and they do not react to light.
- e. 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.
- f. If the brain stem down through the pons-medulla is involved, the pupils continue to be midposition and fixed.
- g. However, if the pons or medulla is selectively involved (with preservation of midbrain function) the pupils will be small and reactive because only the descending sympathetic pathways are damaged. For example, with pontine transection the pupils are frequently 1mm or smaller. There remains very little potential for further pupil constriction, and for practical purposes at the bedside, the pupils appear unreactive to light unless a very bright light is used and observations are made with a magnifying glass. A similar situation occurs with narcotic overdose, where the pupils may be maximally constricted (pinpoint, 0.5 mm or less) and therefore unreactive to light.
- h. Suppression of brain stem function (such as by drugs, toxins or metabolic upsets) can abolish the pupillary light reflex. However, this reflex is the most resistant brain stem function when it comes to metabolic 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 Chap. 6).
One of the most important determinations that can be made in the comatose patient is whether there is normal oculomotor-vestibular function. This is because the reflexes involved traverse the brain stem adjacent to the reticular activating system. Additionally, in the patient with an awake and alert cerebral cortex, there are competing reflexes that produce a distinctive pattern of eye movements. Therefore, this single assessment can determine whether the brain stem reticular formation is intact and how alert the cerebral cortex is.
- a. Diffuse cerebral cortical damage or suppression of cortical function results in loss of the fast component of the vestibulo-ocular reflex. The degree of suppression of this fast component is proportional to the degree of suppression/damage. 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.
- b. Damage to the mesencephalon produces loss of medial rectus response to caloric and oculocephalic stimulation, with intact lateral rectus function. The corneal reflex will be preserved since this is mediated at the pontine level.
- c. 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 Chap. 8).
- a. With impairment of cerebral cortical function, paratonia is present. This is an active perseveration of position in the limbs when passively manipulated (it feels like the patient is actively resisting your attempts to passively move the limbs and presents as irregular resistance). The mechanism of this phenomenon is not known but is also present in normal children (and therefore may represent a normal primitive response). It can be seen in some normal individuals. In addition to paratonia, the patient with depressed cortical function may have a range of motor responses to noxious stimuli. They may localize the stimulus, reaching to remove the irritant, or they may simply withdraw the body part. The latter response is less organized and occurs, to some extent, even with complete cessation of cerebral cortical function.
- b. With damage to the diencephalon decorticate posturing may be seen following noxious stimulation (see Fig. 8-1). Decorticate posturing includes flexion of the arm, wrist and fingers, with extension of the lower limbs. This posturing may be asymetrical initially (appearing first on the more damaged side).
- c. With damage to 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 Fig. 8-1).
- d. Damage to the lower pons and medulla eliminates the response to noxious stimuli. Acute cross-sectional loss of the lower pons almost invariably results in flaccid quadriplegia. The flaccid state, as noted in Chapter 8, is considered a diaschisis or shock phenomenon and 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 include tumors, abscesses or hemorrhage but also can include edema, whatever the initial cause of the injury. Expanding masses result in rostral-caudal deterioration of neural function which can be observed in patients in whom the process cannot be stopped. In this model, cortical function is affected first, followed by dysfunction of the diencephalon, then midbrain (often due to herniation of the uncus of the medial temporal lobe), then pons and medulla. Fig. 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 (i.e., left hemiparesis, left hemisensory defect, left visual field deficit). However, when expansion of the mass results in bilateral pressure on the upper brain stem (i.e., diencephalon), characteristic changes in these 5 variables will begin to occur. The progression of deterioration usually occurs in 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 with loss of the corneal reflex); and the motor response will go from normal mobility, through paratonia, 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 didactic 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 when the process has extended beyond the midbrain. When loss of midbrain function is complete in acute deterioration, secondary hemorrhages (Duret hemorrhages) develop into the midbrain and pontine tegmentum in most patients, signaling the permanent cessation of reticular activating system function. These are presumed to occur secondary to traction and tearing of the paramedian vessels penetrating from the major basal arteries (basilar and posterior cerebral arteries). Therefore it is extremely important to recognize rostrocaudal deterioration early in order to institute therapy to prevent progression.
The cerebral cortex is more susceptible to toxic, metabolic or drug-related suppression of activity than is the brain stem. Therefore, metabolic suppression of neural functions initially tends to spare brain stem reflexes and, until very late in the process, spares primitive brain stem functions (oculovestibular, respiratory and pupillary functions) until late. The pupils are usually the last reflex to be detected with metabolic suppression, although a magnifying lens (or otoscope) and a very bright light may be necessary to detect the pupillary response. These case examples will elaborate on the various presentations of metabolic encephalopathy.
We would like to draw your attention to a single important reference for further reading on the subject of stupor and coma. The information in this chapter is considered a primer based largely on the classic text: Diagnosis of Stupor and Coma by Fred Plum and Jerome Posner. Clarity and comprehensive coverage make their book required reading and reference for all physicians who deal with patients who have depressed levels 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, this causes varying degrees of loss of cognitive and emotional function. However, if this 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 such as may result from hypoxia (often due to pneumonitis), sepsis or renal failure from chronic urinary tract infection, or simply malnutrition, all of which depress further the functions of the cerebral hemispheres.
- 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?