Neurology_Adams

Neurology_Adams. A distinction is made in medicine between the level of consciousness and the content of consciousness, the latter reflecting the quality and coherence of thought and behavior. For neurological purposes, the loss of normal arousal is the dramatic aspect of disordered consciousness and the one identified by laypersons and physicians as being the central feature of coma. However, the state of confusion, or delirium is more ubiquitous and caused by a large variety endogenous and exogenous disorders, and the bizarre and illogical qualities of psychosis are a component of the study of psychiatric disease.


Neurology_Adams

Neurology_Adams. Much more could be said about the history of our ideas concerning consciousness, and the theoretical problems with regard to its definition. There has been an ongoing polemic among philosophers of mind as to whether it will ever be possible to understand mind and consciousness in terms of reductionist physical entities, such as cellular and molecular neural systems. Although it serves little practical purpose to review these subjects here, we note that contemporary investigations indicate that one constructive approach is to define the neurobiologic correlates of those elements of clinical consciousness that are subject to observation by behavioral, electrical, and particularly imaging methods. Importantly, these controversies are informed in neurology by analyses of those neurologic disorders that disturb perception and consciousness of perception (phantom limb, “blindsight,” etc.). The interested reader is referred to the discussions of consciousness by Crick and Koch, Plum and


Neurology_Adams

Neurology_Adams. disorders that disturb perception and consciousness of perception (phantom limb, “blindsight,” etc.). The interested reader is referred to the discussions of consciousness by Crick and Koch, Plum and Posner, Young, and Zeman listed in the references.


Neurology_Adams

Neurology_Adams. The following definitions are of service to clinicians and provide a convenient terminology for describing the states of awareness and responsiveness of patients. This is the condition of the normal person when awake. In this state the individual is fully responsive to a thought or perception and indicates by his behavior and speech the same awareness of self and environment as that of the examiner. There is attention to, and interaction with, the immediate surroundings. This normal state may fluctuate during the day from one of keen alertness or deep concentration with a marked constriction of the field of attention to one of mild general inattentiveness, but even in the latter circumstances, the normal individual can be brought immediately to a state of full alertness and function.


Neurology_Adams

Neurology_Adams. The term confusion admittedly lacks precision, but in operational terms it denotes an inability to think with customary speed, clarity, and coherence. Almost all states of confusion are marked by some degree of inattentiveness and disorientation and for some investigators, these two qualities define the state. In this condition the patient does not take into account all elements of his immediate environment. This state also implies a degree of imperceptiveness and distractibility, referred to in the past as “clouding of the sensorium.” Here, one difficulty is to define thinking, a term that refers variably to problem solving or to coherence of ideas. Confusion results most often from a process that influences the brain globally, such as a toxic or metabolic disturbance or a dementia. In addition, any condition that causes drowsiness or stupor, including the natural state that comes from sleep deprivation, results in some degradation of mental performance and the emergence of


Neurology_Adams

Neurology_Adams. In addition, any condition that causes drowsiness or stupor, including the natural state that comes from sleep deprivation, results in some degradation of mental performance and the emergence of inattentiveness and a state of confusion. In this way, confusion, which exists along the axis of content of consciousness, is linked to alertness and the level of consciousness.


Neurology_Adams

Neurology_Adams. A confusional state can also accompany focal cerebral disease, particularly in the right hemisphere, or result from focal disorders that disturb mainly language, memory, or visuospatial orientation, but a distinction is made between these isolated disruptions in mental function and the global confusional state. They represent special states that are analyzed differently, matters discussed further in Chaps. 19 and 21. The mildest degree of confusion may be so slight that it can be overlooked unless the examiner searches for deviations from the patient’s normal behavior and ability to carry on a coherent conversation. The patient may even be roughly oriented as to time and place, with only occasional irrelevant remarks betraying a lack of clarity and slowness of thinking. Their responses are inconsistent, attention span is reduced, and they are unable to stay on one topic, together suggesting a fundamental flaw in attention.


Neurology_Adams

Neurology_Adams. As mentioned this is usually accompanied by disorientation and distractibility, leaving the patient at the mercy of every stimulus. In parallel, sequences of movement reveal impersistence and poor planning. Severely confused and inattentive persons are unable to do more than carry out the simplest commands, and these only inconsistently and in brief sequence. Speech may be limited to a few words or phrases; or the opposite pertains—namely, some confused individuals are voluble. They give the appearance of being unaware of much that goes on around them, are disoriented in time and place, do not grasp their immediate situation or the predicament of their own confusion, and may misidentify people or objects. These illusions may lead to fear or agitation. Occasionally, hallucinatory, illusionary, or delusional experiences impart a psychotic cast to the clinical picture, obscuring the deficit in attention.


Neurology_Adams

Neurology_Adams. Many events that involve the confused patient leave no trace in memory; in fact, the capacity to recall events of the past hours or days is one of the most delicate tests of mental clarity. Another is the use of “working memory,” which requires the temporary storage of the solution of one task for use in the next. A deficit in working memory, which is a common feature of the confusional states, can be demonstrated by tests of serial subtraction, and the spelling of words (or repeating a phone number) forward and then backward. Careful analysis will show these defects to be tied to impaired registration of information rather than to a fault in memory. These phenomena again betray inattention as central features of most confusional states. As already stated, the observed behavior of a confused person transcends inattention alone. It may incorporate elements of clouded interpretation of internal and external experience, and an inability to integrate and attach symbolic meaning to


Neurology_Adams

Neurology_Adams. a confused person transcends inattention alone. It may incorporate elements of clouded interpretation of internal and external experience, and an inability to integrate and attach symbolic meaning to experience (apperception). The degree of confusion often varies from hour to hour and one time of day to another. It tends to be least pronounced in the morning and increases as the day wears on, peaking in the early evening hours (“sundowning”) when the patient is fatigued, and environmental cues are not as clear.


Neurology_Adams

Neurology_Adams. In most current medical writings, particularly in the psychiatric literature, the terms delirium and confusion are used interchangeably, the former connoting nothing more than a nondescript confusional state. However, in the syndrome of delirium tremens (observed most often but not exclusively in alcoholics), the vivid hallucinations; extreme agitation; trembling, startling easily, and convulsion; and the signs of overactivity of the autonomic nervous system suggest to us that the term delirium should be retained for this type of distinctive confusional syndrome (elaborated in Chap. 19). As commented earlier, a relationship between the level of consciousness and progressively disordered thinking, namely confusion, is evident as patients pass through states of inattention, drowsiness, confusion, stupor, and coma.


Neurology_Adams

Neurology_Adams. Drowsiness denotes an inability to sustain a wakeful state without the application of external stimuli. Mental, speech, and physical activity are reduced. The state is indistinguishable from light sleep, sometimes including slow arousal elicited by speaking to the patient or applying a tactile stimulus. Furthermore, in distinction to stupor discussed later, drowsy individuals sustain alertness for at least some brief period, without the further necessity of external stimuli. As a rule, some degree of inattentiveness and mild confusion are coupled with drowsiness, both improving with arousal. The patient shifts positions somewhat naturally and without prompting. The lids droop; there may be snoring, the jaw and limb muscles are slack, and the limbs are relaxed.


Neurology_Adams

Neurology_Adams. Stupor describes a state in which the patient can be roused only by vigorous and repeated stimuli and in which arousal cannot be sustained without repeated stimulation. Responses to spoken commands are either absent, curtailed, or slow and inadequate. Restless or stereotyped motor activity is common, and there is a reduction or elimination of the natural shifting of body positions. When left unstimulated, these patients quickly drift back into a deep sleep-like state. The eyes are usually found to be displaced outward and upward, a feature that is shared with sleep (see further on). Tendon and plantar reflexes, and the breathing pattern may or may not be altered, depending on how the underlying disease has affected the nervous system. In psychiatry, the term stupor had been used in a second sense—to denote an uncommon condition in which the perception of sensory stimuli is presumably normal but activity is suspended and motor activity is profoundly diminished (catatonia, or catatonic


Neurology_Adams

Neurology_Adams. sense—to denote an uncommon condition in which the perception of sensory stimuli is presumably normal but activity is suspended and motor activity is profoundly diminished (catatonia, or catatonic stupor).


Neurology_Adams

Neurology_Adams. These states, including coma, exist in a continuum, and an alternative practical method of making distinctions between them was given by Fisher, who suggested that a verbal command is required to overcome drowsiness whereas a noxious stimulus is required to overcome stupor. This allows for further gradations in the level of consciousness based on the intensity of stimulation that is necessary to produce arousal.


Neurology_Adams

Neurology_Adams. The patient who is incapable of being aroused by external stimuli or inner need, comatose. There are variations in the degree of coma, and the findings and signs depend on the underlying cause of the disorder. In its deepest stages, no meaningful or purposeful reaction of any kind is obtainable and corneal, pupillary, pharyngeal responses are diminished. In lighter stages, sometimes referred to by the ambiguous terms semicoma or obtundation, most of the above reflexes can be elicited, and the plantar reflexes may be either flexor or extensor (Babinski sign). As mentioned, the depth of coma and stupor may be gauged by the response to externally applied stimuli and is most useful in assessing the direction in which the disease is evolving, particularly when compared in serial examinations. Relationship of Sleep to Coma


Neurology_Adams

Neurology_Adams. Persons in sleep give little evidence of being aware of themselves or their environment; in this respect, they are unconscious. Sleep shares a number of other features with the pathologic states of drowsiness, stupor, and coma. These include yawning, closure of the eyelids, cessation of blinking and reduction in swallowing, upward deviation or divergence or roving movements of the eyes, loss of muscular tone, decrease or loss of tendon reflexes, and even the presence of Babinski signs and irregular respirations, sometimes Cheyne-Stokes in type. Upon being awakened from deep sleep, a normal person may be confused for a few moments, as every physician knows from personal experience. Nevertheless, sleeping persons may still respond to unaccustomed stimuli and are capable of some mental activity in the form of dreams that leave traces of memory, thus differing from stupor or coma. The most important difference, of course, is that persons in sleep, when stimulated, can be roused to normal


Neurology_Adams

Neurology_Adams. in the form of dreams that leave traces of memory, thus differing from stupor or coma. The most important difference, of course, is that persons in sleep, when stimulated, can be roused to normal and persistent consciousness. There are important physiologic differences as well. Cerebral oxygen uptake does not decrease during sleep, as it usually does in coma. Recordable electrical activity—electroencephalographic (EEG) and cerebral evoked responses—and spontaneous motor activity differ in the two states, as indicated later in this chapter and in Chap. 18. The anatomic and physiologic bases for these differences are only partly known.


Neurology_Adams

Neurology_Adams. THE VEGETATIVE AND MINIMALLY CONSCIOUS STATES, LOCKED-IN SYNDROME, AND AKINETIC MUTISM Several clinical conditions are juxtaposed to the continuum of drowsiness, stupor and coma. They stand apart as a result of special characteristics or by their underlying cause but, with the exception of the locked in state, they are each forms of diminished consciousness.


Neurology_Adams

Neurology_Adams. With increasing refinements in the treatment of severe systemic diseases and cerebral injury, larger numbers of patients, who formerly would have died, have survived for indefinite periods without regaining any meaningful mental function. For the first week or two after severe cerebral injury, these patients are in a state of deep coma. Then they begin to open their eyes, at first in response to painful stimuli, and later spontaneously and for increasingly prolonged periods. The patient may blink in response to threat or to light and intermittently the eyes move from side to side, seemingly following objects or fixating momentarily on the physician or a family member and giving the erroneous impression of recognition. Respiration may quicken in response to stimulation, and certain automatisms—such as swallowing, bruxism, grimacing, grunting, and moaning—may be observed (Zeman). However, the patient remains unresponsive and, for the most part, unconscious, does not speak, and shows no


Neurology_Adams

Neurology_Adams. as swallowing, bruxism, grimacing, grunting, and moaning—may be observed (Zeman). However, the patient remains unresponsive and, for the most part, unconscious, does not speak, and shows no signs of awareness of the environment or inner need; motor activity is limited to primitive postural and reflex movements of the limbs. There is loss of sphincter control. There may be arousal or wakefulness in alternating cycles as reflected in partial eye opening, but the patient regains neither awareness nor purposeful behavior.


Neurology_Adams

Neurology_Adams. These features define the vegetative state. One sign of the vegetative state is a lack of consistent visual following of objects, particularly because brief observation of ocular movements is subject to misinterpretation, and repeated examinations are required. These perspectives on the completeness of unresponsivity represent conventional thinking and have been partly altered by the findings of some conscious activity that can be detected by functional imaging with certain commands and verbal cues such as the individual’s name as detailed below.


Neurology_Adams

Neurology_Adams. If the vegetative syndrome of unconscious awakening persists for 3 months after nontraumatic brain injury, and 12 months after traumatic injury, the syndrome has been termed the persistent vegetative state (PVS; Jennett and Plum). These terms have gained acceptance and apply to the clinical appearance whatever the underlying cause. Additional terms that have been used to describe this syndrome of preserved autonomic and respiratory function without cognition include apallic syndrome (also called awake unawareness) and neocortical death. A position paper has codified the features of the PVS and suggests dropping a number of related ambiguous terms, although some, such as akinetic mutism, discussed further on, have a more specific neurologic meaning and are still useful (see Multi-Society Task Force on PVS).


Neurology_Adams

Neurology_Adams. The most common pathologic bases of the vegetative state are diffuse cerebral injury as a result of closed head trauma, widespread necrosis of the cortex after cardiac arrest or other form of anoxia, and thalamic necrosis from a number of causes. The vegetative state or the minimally conscious state described further on, may also be the terminal phase of progressive cortical degenerative processes such as Alzheimer and Creutzfeldt-Jakob disease (where the pathologic changes are mainly cortical but may include the thalamus).


Neurology_Adams

Neurology_Adams. It is worth noting again that the prominent pathologic changes are often in the thalamic and subthalamic nuclei, as in the widely known Quinlan case (Kinney et al) rather than solely in the cortex as often stated; this holds for postanoxic as well as traumatic cases. A review by J.H. Adams and colleagues found these thalamic changes, but attributed them to secondary degeneration from white matter and cortical lesions. However, in several of our cases the thalamic damage stood almost alone as the cause of persistent “awake coma.” In traumatic cases, the pathologic findings are often of diffuse subcortical white matter degeneration (described as diffuse axonal injury), prominent thalamic degeneration, and ischemic damage in the cortex. Further insight is found in a study of brain morphometry by MRI undertaken by Lutkenhoff and colleagues, who determined that in patients with early vegetative or minimally conscious states there was global brain atrophy but the thalamic and basal


Neurology_Adams

Neurology_Adams. by MRI undertaken by Lutkenhoff and colleagues, who determined that in patients with early vegetative or minimally conscious states there was global brain atrophy but the thalamic and basal ganglionic structures were disproportionately affected.


Neurology_Adams

Neurology_Adams. Taken together, these anatomic findings indicate that PVS is a state in which the cortex is either diffusely injured or effectively disconnected and isolated from the thalamus, or the thalamic nuclei are destroyed. In either the traumatic or anoxic types of PVS, atrophy of the cerebral white matter leads to secondary ventricular enlargement and thinning of the corpus callosum.


Neurology_Adams

Neurology_Adams. These observations notwithstanding, there is little doubt that the neuroanatomic and neurophysiologic basis of the vegetative state will prove to be complex or at least separable into categories defined by the locus of brain damage. In particular, a striking observation has been made by Owen and colleagues in a 23-year-old woman who had been vegetative for 5 months after a head injury. They observed localized cortical activity in the middle and superior temporal gyri in response to the presentation of spoken sentences that was comparable to the brain activity in normal individuals. Di and colleagues have similarly demonstrated in a limited proportion of vegetative patients that there can be brain activation to the patient’s own name and not to other names. These data suggest that some forms of mental processing can go on during a vegetative state but it is not clear if this situation is representative nor does it provide information about self-awareness, a requisite for consciousness.


Neurology_Adams

Neurology_Adams. of mental processing can go on during a vegetative state but it is not clear if this situation is representative nor does it provide information about self-awareness, a requisite for consciousness. Further compelling demonstration of cognitive processing in vegetative and minimally conscious patients has been provided by Monti and colleagues by functional MRI. Five of their 54 patients, all with traumatic brain injury but none after anoxic ischemic damage, could willfully modulate focal brain activity by imagining playing tennis (frontal lobe activation) or mentally navigating a familiar place such as their home (temporal lobe activation). In one patient, this activity was used as a means of communication.


Neurology_Adams

Neurology_Adams. At a minimum, these demonstrations emphasize the care that must be taken in establishing diagnoses of PVS and minimally conscious states. Whether these findings with functional imaging simply reflect preserved islands of function in severe brain injury that cannot be examined clinically or whether they require an entire rethinking of the neurologic examination that determines the state of consciousness cannot yet be stated (see editorial by Ropper, 2010).


Neurology_Adams

Neurology_Adams. An additional observation of some consequence is the finding of purported axonal growth over time in a patient with traumatic brain injury who had been in a minimally conscious state (see below) for 19 years and then began to speak and comprehend, while remaining virtually quadriplegic. Voss and colleagues, using sophisticated MRI diffusion tensor imaging, have shown axonal sprouting in the posterior parietal and midline cerebellar regions. They compared the results of tensor imaging to a patient who had been in a minimally conscious state for 6 years without improvement and to 20 normal individuals. Their findings are subject to several interpretations, but axonal growth in the parietal lobes offers a potential explanation for the few instances in which recovery from severe injury does occur. When combined with the findings of Laureys and colleagues, a case can be made for the posterior parietal regions as necessary for integrated consciousness and also raise the possibility that


Neurology_Adams

Neurology_Adams. occur. When combined with the findings of Laureys and colleagues, a case can be made for the posterior parietal regions as necessary for integrated consciousness and also raise the possibility that certain islands of limited awareness may be dissociated from global brain function.


Neurology_Adams

Neurology_Adams. It is difficult to predict which comatose patients will later fall permanently into the vegetative or minimally conscious categories. Plum and Posner reported that of 45 patients with signs of the vegetative state at 1 week after onset, 13 had awakened and 5 of these had satisfactory outcomes. After being vegetative for close to 2 weeks, only 1 recovered to a level of moderate disability; after 2 weeks, the prognosis was uniformly poor. Larger studies by Higashi and colleagues have given similar results. As a rough guide to prognosis specifically in head injury, Braakman and colleagues found that among a large group of comatose patients, 59 percent regained consciousness within 6 h, but of those in a vegetative state at 3 months, none became independent. At no time before 3 or 6 months was it possible to distinguish patients who would remain in a vegetative state from those who would die. Further comments regarding recovery are made in the next section on the minimally conscious


Neurology_Adams

Neurology_Adams. was it possible to distinguish patients who would remain in a vegetative state from those who would die. Further comments regarding recovery are made in the next section on the minimally conscious state.


Neurology_Adams

Neurology_Adams. A study by the Multi-Society Task Force on PVS concluded that the outcome from a vegetative state is better in traumatic as compared to nontraumatic cases. J.H. Adams and coworkers have proposed that this reflects differences in the state of thalamic neurons in the two situations. They suggested that after acute hypoxia, neurons subjected to ischemic necrosis are liable to be permanently lost; by contrast, in trauma, the loss of thalamic neurons is more frequently secondary to transsynaptic degeneration following diffuse axonal injury, allowing a greater potential for recovery. Many of these ideas are speculative.


Neurology_Adams

Neurology_Adams. Laboratory features The vegetative state is associated with a grossly abnormal EEG and is characterized by one of a number of abnormal patterns. There may be predominantly low-amplitude delta-frequency background activity, burst suppression, widespread alpha and theta activity, an alpha coma pattern, and sleep spindles, all of which have been described in this syndrome, as summarized by Hansotia (see Chap. 2). One important feature is a lack of the normal change in the background EEG activity during and immediately after stimulating the patient.


Neurology_Adams

Neurology_Adams. In all these clinical states, the profound and widespread dysfunction of the cerebrum is also reflected by extreme reductions in cerebral blood flow and metabolism, measured with positron emission tomography (PET) and other techniques. On the basis of PET studies in a patient with carbon monoxide poisoning, Laureys and colleagues observed that the main difference between the vegetative state and the later state in which the patient has recovered was the degree of hypometabolism in the parietal lobe association area. Anatomic changes in this same cortical region have been implicated in the transition from minimally conscious to a more awake state. The finding in PET studies that noxious somatosensory stimulation fails to activate the association cortices is consistent with the concept that large regions of cortex are isolated from thalamic input or that the critical parietal interpretive areas are isolated from the rest of the cortex.


Neurology_Adams

Neurology_Adams. Of practical value is the observation that the CT and MRI may show progressive and profound cerebral atrophy in cases of vegetative state. In the absence of this atrophy after several months or more, it may be unwise to offer a pessimistic prognosis.


Neurology_Adams

Neurology_Adams. The vegetative state blends into a less severe but still profound dementia that has been termed “minimally conscious state,” wherein the patient is capable of some rudimentary behavior such as following a simple command, gesturing, or producing single words or brief phrases, always in an inconsistent way from one examination to another (see Giacino et al). There is preservation of the ability to carry out basic motor behaviors that demonstrate a degree of awareness. The minimally conscious state is found as a transitional or permanent condition and is sometimes difficult to separate from akinetic mutism discussed further on. Any notion of such a patient’s self-awareness is conjectural, but there may be an impressive array of behaviors and activation of associative regions of the cerebral cortex that suggest that processing of external information is taking place beyond a rudimentary level (see discussion by Bernat). The causes and pathologic changes underlying the minimally conscious


Neurology_Adams

Neurology_Adams. cortex that suggest that processing of external information is taking place beyond a rudimentary level (see discussion by Bernat). The causes and pathologic changes underlying the minimally conscious state are identical to those of the vegetative state, including the frequent finding of thalamic and multiple cerebral lesion. Viewed from on perspective, the distinction between them is one of degree.


Neurology_Adams

Neurology_Adams. It is useful to maintain a critical view of reports of remarkable recuperation after months or years of prolonged coma or the vegetative state. When the details of such cases become known, it is sometimes evident that recovery might reasonably have been expected. There are, however, numerous reported instances of partial recovery in patients—particularly children and young adults—who display vegetative features for several weeks or, as Andrews and Childs and Mercer describe, even several months after injury. Such observations cast doubt on unqualified claims of success with certain therapies, such as specialized sensory stimulation. Nevertheless, the rare occurrence of late recovery in adults must be acknowledged (see Andrews; Higashi et al; and Rosenberg et al, 1977) and a relation of awakening to the recovery of connections to the parietal lobes has already been mentioned.


Neurology_Adams

Neurology_Adams. Cases of improvement from the “minimally conscious state” are more plausible than those from the vegetative state. Contrasting the notion that late recovery is exceptional, a case series reported by Estraneo and colleagues of 50 consecutive patients in PVS for a year, 10 showed improvement at an average of 2 years but all were severely impaired. In the series by Luaté and coworkers, none of 12 vegetative patients improved at 5 years but 13 of 39 minimally conscious cases emerged to consciousness with severe disability. Of course, the application of these terms to a patient often leads to the withdrawal of care, and a self-fulfilling poor prognosis. This is a much discussed problem that has not been satisfactorily addressed but it emphasizes that simply labeling patients with PVS or MCS has implications for accurately assessing the natural history of some diseases.


Neurology_Adams

Neurology_Adams. Among recent therapeutic observations, one observation has come from Schiff and colleagues, who were able to improve function by stimulating the medial (intralaminar) thalamic nuclei through implanted electrodes in a patient who had been initially vegetative and had made a natural transition to a minimally conscious state after traumatic brain injury. Longer periods of eye opening and increased responses to execute commands, such as bringing a cup to his mouth, were observed, including, for the first time since his injury, intelligible verbalization. The authors point out that this individual had preserved language cortex and connections between thalamus and cortex. Whether this remarkable result is generalizable is not known.


Neurology_Adams

Neurology_Adams. It must be remarked that the degree of disability that families find acceptable varies greatly and leads to difficult decisions regarding the continuation of medical care. The knowledgeable, sympathetic, and flexible physician is in the best position to offer perspective and guide these matters over the long periods of time required, as discussed at the end of this chapter.


Neurology_Adams

Neurology_Adams. The states of coma described above and the vegetative state must be distinguished from a syndrome in which there is little or no disturbance of consciousness, but only an inability of the patient to respond adequately with motor activity and speech. This condition is referred to as the locked-in syndrome or the deefferented state. The term pseudocoma as a synonym for this state is best avoided, because it is used by some physicians to connote the unconsciousness of the hysteric or malingerer, the dissociative state, or catatonia. The locked-in syndrome is most often caused by a large lesion of the ventral pons (basis pontis), usually as a result of occlusion of the basilar artery. Such infarctions spare both the somatosensory pathways, and the ascending neuronal systems responsible for arousal and wakefulness, as well as certain midbrain elements that allow the eyelids to be raised in wakefulness. The damage essentially completely interrupts the descending corticobulbar and


Neurology_Adams

Neurology_Adams. for arousal and wakefulness, as well as certain midbrain elements that allow the eyelids to be raised in wakefulness. The damage essentially completely interrupts the descending corticobulbar and corticospinal tracts, depriving the patient of speech and the capacity to respond in any way except by voluntary vertical gaze and by blinking. Severe motor neuropathy (e.g., Guillain-Barré syndrome), pontine myelinolysis, or periodic paralysis may produce a similar effect.


Neurology_Adams

Neurology_Adams. One could logically refer to the locked-in state as akinetic mutism insofar as the patient is akinetic (motionless) and mute, but this is not the sense in which the term was originally used by Cairns and colleagues, who described a patient who gave the appearance of being awake but was unresponsive (actually, their patient was able to answer in whispered monosyllables). Following each of several drainings of a third ventricular cyst, the patient again became responsive but had no memory of events that had taken place when she was in the akinetic mute state. This state of apparent vigilance in an imperceptive and unresponsive patient has been referred to by French authors as coma vigile, but this is also confusing because the same term has been applied to the vegetative state.


Neurology_Adams

Neurology_Adams. The term akinetic mutism has been applied to yet another group of patients who are silent and inert as a result of bilateral lesions of the anterior parts of the frontal lobes or in the thalamus, leaving intact the motor and sensory pathways. The patient is profoundly apathetic, lacking to an extreme degree the psychic drive or impulse to action. There is a marked delay in verbal and motor responses (abulia), however, the abulic patient, unlike Cairns’ patient, registers most of what is happening about him and if intensely stimulated, may speak normally, relating events observed in the recent and distant past.


Neurology_Adams

Neurology_Adams. The patient with catatonia appears unresponsive, in a state that simulates stupor, light coma, or akinetic mutism. There are no signs of structural brain disease, such as pupillary or reflex abnormalities. As in the normal awake state, oculocephalic responses are muted—that is, the eyes move concurrently with the head as it is turned. There is usually resistance to eye opening, and some patients display a waxy flexibility of passive limb movement that gives the examiner a feeling of bending a wax rod (flexibilitas cerea); there may also the retention for a long period of seemingly uncomfortable limb postures (catalepsy). Peculiar motor mannerisms or repetitive motions, seen in a number of these patients, may give the impression of seizures; choreiform jerking has also been reported, but the latter sign should also suggest the possibility of seizure activity. The EEG shows normal posterior alpha activity that is attenuated by stimulation. Catatonia is discussed further in Chaps. 19 and


Neurology_Adams

Neurology_Adams. latter sign should also suggest the possibility of seizure activity. The EEG shows normal posterior alpha activity that is attenuated by stimulation. Catatonia is discussed further in Chaps. 19 and 49.


Neurology_Adams

Neurology_Adams. Because there is considerable imprecision in the use of terms by which the states of reduced consciousness are designated, the physician is better advised to supplement designations such as coma and akinetic mutism by simple descriptions indicating whether the patient appears awake or asleep, drowsy or alert, aware or unaware of his surroundings, and responsive or unresponsive to a variety of stimuli. This requires that the patient be observed more for a longer period and more frequently than the several minutes usually devoted to this portion of the neurologic examination. The aforementioned findings of responsiveness reflected by functional imaging in a clinically unresponsive patient further emphasizes the care with which these clinical diagnoses should be proffered.


Neurology_Adams

Neurology_Adams. In the late 1950s, European neurologists called attention to a state of coma in which the brain was irreversibly damaged and had ceased to function, but pulmonary and cardiac function could still be maintained by artificial means. Mollaret and Goulon referred to this condition as coma dépassé (a state beyond coma). A Harvard Medical School committee in 1968 called it brain death and established a set of clinical criteria by which it could be recognized (see Beecher et al; the report is often said to be from the “Beecher Committee”). R.D. Adams, who was a member of the committee, defined the state as one of complete unresponsiveness to all modes of stimulation, arrest of respiration, and absence of all EEG activity for 24 h. The concept that a person is dead if the brain is dead and that death of the brain may precede the cessation of cardiac function has over the years posed a number of important ethical, legal, and social problems, as well as medical ones. All aspects of brain death


Neurology_Adams

Neurology_Adams. of the brain may precede the cessation of cardiac function has over the years posed a number of important ethical, legal, and social problems, as well as medical ones. All aspects of brain death have since been the subject of close study by several professional and governmental committees, which for the most part have followed the 1968 guidelines for determining that the brain is dead and equating this state with the traditional version of death as the inevitable dissolution of the body after cardiac and respiratory function have permanently ceased. The American Academy of Neurology published guidelines on this subject in 1995 and affirmed them with some refinements in 2010. The monograph by Wijdicks is a comprehensive modern source on the subject of brain death and also addresses the subject from an international perspective.


Neurology_Adams

Neurology_Adams. The philosophical underpinnings of the equating of brain death to death, giving it the same status as cessation of cardiorespiratory death, are more complex. In particular, the ethical and moral dimensions of brain death are subject to differing interpretations in various societies, religions, and cultures. Some of these are reviewed in a perspective article by the prominent writers Magnus, Wilford, and Caplan, who suggest that the wide medical and societal acceptance of brain death makes it an important construct, not to be abandoned because of philosophical objections. One justification for equating brain death with somatic death is the general inevitability of cardiorespiratory failure in patients who fulfill the standard criteria. This tenet has exceptions, among the most striking of which is a well-studied case of 20-year survival in a boy who had meningitis reported by Reptinger and colleagues, and other cases of long that have been described with varying degrees of


Neurology_Adams

Neurology_Adams. striking of which is a well-studied case of 20-year survival in a boy who had meningitis reported by Reptinger and colleagues, and other cases of long that have been described with varying degrees of documentation. These have been collected by Shewmon who makes the point that arguments equating brain death with death on the basis of the brain’s role in creating “somatic unity” are weakened by the existence of such long surviving cases as well as by delivery of live babies from brain-dead mothers. Further clouding the issue of validity of brain death is the proposal by British and Scandinavian neurologists that death of the brainstem alone is adequate to fulfill the precepts of brain death. In the end, these philosophical concerns truly matter but the operational state called brain death at the moment serves both patients and society well and is compatible with most of the world’s religions.


Neurology_Adams

Neurology_Adams. The central considerations in the diagnosis of brain death are (1) absence of all cerebral functions; (2) absence of all brainstem functions, including spontaneous respiration; and (3) irreversibility of the state. Following from the last of these criteria, it is necessary to demonstrate an irrefutable cause of the underlying catastrophic brain damage (e.g., trauma, cardiac arrest, cerebral hemorrhage) and to exclude reversible causes such as drug overdose and extreme hypothermia.


Neurology_Adams

Neurology_Adams. In the diagnosis of brain death, the absence of cerebral function is demonstrated by the presence of deep coma and total lack of spontaneous movement and of motor and vocal responses to all visual, auditory, and cutaneous stimulation. Spinal reflexes (deep tendons reflexes) may persist, and the toes often flex slowly in response to plantar stimulation; but a well-developed Babinski sign is unusual (although its presence does not exclude brain death). Extensor or flexor posturing is seen from time to time as a transitional phenomenon just before or after brain death becomes evident, and the status of these movements in the diagnosis is ambiguous, but most criteria consider these movements to be incompatible with brain death, as they reflect functioning of brainstem centers. The physician should therefore proceed cautiously in declaring a patient dead in the presence of posturing and should consider conducting the examination again at a later time.


Neurology_Adams

Neurology_Adams. The complete absence of brainstem function is judged by the loss of spontaneous eye movements, the resting position of both globes at the meridian of the palpebral fissures, and lack of response to oculocephalic and caloric (vestibulo-ocular) testing; the presence of dilated or midposition fixed pupils (not smaller than 3 mm); paralysis of bulbar musculature (no facial movement or gag, cough, corneal, or sucking reflexes); absence of motor and autonomic responses to noxious stimuli; and absence of respiratory movements. The clinical findings should show complete absence of brain function, not an approximation that might be reflected, for example, by small or poorly reactive pupils, slight eye deviation with oculovestibular stimulation, or posturing of the limbs, as mentioned earlier.


Neurology_Adams

Neurology_Adams. As a demonstration of destruction of the medulla, it has become customary to perform an “apnea test” to demonstrate unresponsiveness of the medullary centers to a high carbon dioxide tension. This test is conducted by first employing preoxygenation of the lungs for several minutes with high inspired oxygen tension, the purpose of which is to displace nitrogen from the alveoli and create a reservoir of oxygen that will diffuse into the pulmonary circulation. The patient can then be disconnected from the respirator for several minutes, during which time 100 percent oxygen is being delivered by cannula or ventilator that has its pumping mechanism turned off; this allows the arterial PCO2 to rise to above 50 or 60 mm Hg (typically, CO2 rises approximately 2.5 mm Hg/min at normal body temperature—slower if the patient is hypothermic). The induced hypercarbia serves both as a stimulus to breathing and confirms that spontaneous ventilation mediated by medullary centers has failed. (Of


Neurology_Adams

Neurology_Adams. if the patient is hypothermic). The induced hypercarbia serves both as a stimulus to breathing and confirms that spontaneous ventilation mediated by medullary centers has failed. (Of course, peripheral causes of ventilatory failure such as paralytic drugs should not be present.) If no breathing is observed and blood gases show that an adequate level of PCO2 has been attained, this component of brain death is corroborated. Several sets of formal criteria have incorporated a CO2 concentration of 60 mm Hg (7.98 kPa [kilopascals]) as adequate to stimulate the medulla, even under circumstances in which it has been badly damaged. In our experience, patients who have severely brainstem damage but nonetheless breathe and therefore are not brain dead, have shown this activity at a PCO2 well below 50 mm Hg, but there are exceptions in which higher levels are required as a stimulus.


Neurology_Adams

Neurology_Adams. The risks of apnea testing are minimal, as discussed in the American Academy of Neurology’s 2010 document, but hypotension, hypoxemia, cardiac arrhythmias, and lung barotrauma may occasionally occur. In patients who cannot tolerate the test for more than a brief period because it produces hypotension, raising the arterial CO2 by insufflation of this gas has been suggested, but this approach has not been studied extensively. Delivering oxygen during the test with a low tidal volume and a ventilator rate of 1 to 2 breaths per minute or by continuous positive airway pressure may ameliorate hypoxia and resultant hypotension, but this technique has also not been adequately studied.


Neurology_Adams

Neurology_Adams. Most, but not all, brain-dead patients have diabetes insipidus. The absence of this syndrome in some cases reflects the imprecision of the clinical examination in detecting a total loss of brain function. Other ancillary bedside tests may be conducted to corroborate brain death. Among the ones used in special circumstances is the absence of tachycardia in response to the injection of atropine; this reflects the loss of cardiac innervation by damaged medullary vagal neurons.


Neurology_Adams

Neurology_Adams. The authors have observed a number of dramatic spontaneous movements when severe hypoxia is attained following terminal disconnection from the ventilator. These include opisthotonos with chest expansion that simulates a breath, elevation of the arms and crossing them in front of the chest or neck (given the name Lazarus sign by Ropper in 1984), head-turning, shoulder-shrugging, and variants of posturing-like movements. For this reason it may be advisable for the family not to be in attendance immediately after mechanical ventilation has been discontinued.


Neurology_Adams

Neurology_Adams. The EEG provides confirmation of cerebral death, and some institutions prefer to include corroboration by the demonstration of electrocerebral silence (“flat” or, more accurately, isoelectric EEG, shown first by Schwab). However, most U.S. institutions do not require an EEG for the confirmation of death. Electrocerebral silence is considered to be present if there is no electrical potential of more than 2 mV during a 30-min recording except for artifacts created by the ventilator, electrocardiograph, and surrounding electrical devices; as importantly, the absence of these artifacts suggests a technical problem with the recording.


Neurology_Adams

Neurology_Adams. There are cases on record in which a patient with an isoelectric EEG has had preserved brainstem reflexes so that cerebral unresponsiveness and a flat EEG do not alone signify brain death; isoelectric EEG may also be reversible in states of profound hypothermia or intoxication with sedative-hypnotic drugs and immediately following cardiac arrest. Therefore, it has been recommended that the diagnosis of brain death not be entertained until several hours have passed from the time of initial observation. If the examination is performed at least approximately 6 h after the precipitating event, and there is prima facie evidence of overwhelming brain injury from trauma, or massive cerebral hemorrhage (the most common conditions causing brain death), there is probably no need for serial testing. If cardiac arrest was the antecedent event, or the cause of neurologic damage is unclear, or drug or alcohol intoxication could reasonably have played a role in suppressing the brainstem reflexes, it


Neurology_Adams

Neurology_Adams. If cardiac arrest was the antecedent event, or the cause of neurologic damage is unclear, or drug or alcohol intoxication could reasonably have played a role in suppressing the brainstem reflexes, it is advisable to wait about 24 h before repeating the testing and pronouncing the patient dead. Toxicologic screening of the serum or urine is requisite in these circumstances.


Neurology_Adams

Neurology_Adams. The impact of any requirement to perform a second brain death examination at some interval such as 6 h has been studied by Lustbader and coworkers. Their extensive survey in New York State, where a second examination had been recommended by a panel, was instructive; of 1,311 adult and pediatric cases, none who were found to be brain dead regained brainstem function on a second test that was performed about 18 h later. However, 12 percent had cardiac arrest and in others, consent for organ donation was withheld during the time between examinations. Several authoritative authors have argued on this basis against a second brain death test.


Neurology_Adams

Neurology_Adams. Because evoked potentials show variable abnormalities in brain-dead patients, they are probably not of primary value in the diagnosis but if performed, all cerebral activity should be absent. Some centers use nuclide brain scanning or cerebral angiography to demonstrate an absence of blood flow to the brain, equating this with brain death. This approach is acceptable and may be necessary if facial trauma, burns or other injury prevent evaluation of pupillary and ocular reflexes but there are technical pitfalls in the use of these methods. The specificity of radionuclide scanning is close to 100 percent but there is a self-referential aspect to this statement as the clinical diagnosis has been used as a gold standard. An additional problem arises in the observation that the sensitivity may be only about 75 percent (Joffe et al). False-negative tests are possible if a small amount of filling of the intracranial vertebral arteries with angiography or nuclide uptake in the inferior


Neurology_Adams

Neurology_Adams. may be only about 75 percent (Joffe et al). False-negative tests are possible if a small amount of filling of the intracranial vertebral arteries with angiography or nuclide uptake in the inferior cerebellum is demonstrated. The same can be said for a degree of imprecision in transcranial Doppler sonography, which in brain death shows a to-and-fro, pendelfluss blood-flow pattern in the basal vessels.


Neurology_Adams

Neurology_Adams. The main difficulties that arise in relation to brain death are not the technical ones discussed above, but those involving the sensitive conversations with the family of the patient and, to some extent, with other medical professionals. These tasks often fall to the neurologist. It is best not to embark on clinical or EEG testing for brain death unless there is a clear intention on the part of the physician to remove the ventilator or follow through with organ donation at the end of the process. The nature of testing for brain death and its potential outcome should be explained to the family in plain language. The family’s desires regarding organ transplantation should be sought after adequate time has passed for them to absorb the shock of the circumstances. Neurologists must, of course, resist pressures from diverse sources that might lead them to the premature designation of a declaration of brain death. To avoid the appearance of conflict of motivations, most centers have a


Neurology_Adams

Neurology_Adams. resist pressures from diverse sources that might lead them to the premature designation of a declaration of brain death. To avoid the appearance of conflict of motivations, most centers have a separate team, often from an organ bank, to address the issues of organ transplantation after brain death has been established. The complex matter of a family’s desire to maintain ventilation and other medical support in a brain-dead relative is best addressed with consideration and counseling by the physician and clergy, ethics (“optimal care”) committees, and hospital staff, so as to avoid confrontation. Time often allows such situations to be defused.


Neurology_Adams

Neurology_Adams. At the same time, it should be clarified that while brain death is an operational state that allows transplantation to proceed or typically mandates withdrawal of ventilation and blood pressure support, patients with overwhelming brain injuries need not fulfill these absolute criteria in order for medical support to be withdrawn. If the case for recovery is futile and the family and physician agree, of if the patient’s wishes are unequivocally known from preceding documents or discussions, support can be withdrawn in most jurisdictions and the obligate quest for brain death becomes a trap.


Neurology_Adams

Neurology_Adams. A task force for the determination of brain death in children (updated by Nakagawa et al) has recommended the adoption of essentially the same criteria as for adults. However, the difficulty in evaluating the status of nervous function in relation to perinatal insults, has led this group to suggest that the determination not be made before the seventh postnatal day and that the period of observation should be extended to 48 h. As with adults, the possibility of reversible brain dysfunction from toxins, drugs, hypothermia, and hypotension must always be considered.


Neurology_Adams

Neurology_Adams. The EEG provides one of the most delicate confirmations of the fact that states of impaired consciousness are expressions of neurophysiologic changes in the cerebrum. Some form of alteration of brain electrical activity occurs in almost all disturbances of consciousness except for milder degrees of confusion, delirium tremens, and in catatonia, where the preservation of normal background EEG activity can aid in diagnosis. These alterations usually consist of disorganization of the EEG background pattern, including disappearance of the normal alpha rhythm and replacement by random slow waves of low to moderate voltage in the initial stages of confusion and drowsiness; a more regular pattern of slow, 2to 3-per-second waves of high voltage in stupor; slow low-voltage waves or intermittent suppression of organized electrical activity in deep coma of cerebral hypoxia and ischemia; and, ultimately, complete absence of electrical activity in brain death.


Neurology_Adams

Neurology_Adams. The EEG broadly reflects the depth of certain metabolic comas, particularly those caused by hepatic or renal failure. In these conditions, the slow waves become higher in amplitude as coma deepens, ultimately assuming a high-voltage rhythmic delta pattern and a triphasic configuration. Not all cerebral disorders that cause confusion, stupor, and coma have the same effects on the EEG. In cases of intoxication with sedatives, exemplified by barbiturates and diazepines, fast (beta) activity initially replaces normal rhythms. Coma in which myoclonus or twitching is a major clinical feature may show frequent sharp waves or a sharpness of the background slowing of the EEG. A relatively normal EEG is characteristic of delirium tremens as already commented. The differences in EEG changes among metabolic derangements probably represent biologic distinctions at the neuronal level that have not yet been elucidated (see also Chap. 2).


Neurology_Adams

Neurology_Adams. In some deeply comatose patients, the EEG may transiently show diffuse and variable alpha frequency (8to 12-Hz) activity, which may be mistaken for the normal physiologic alpha rhythm. In addition to these aberrant features, the activity displays no reactivity to sensory stimuli. Alpha coma is associated with pontine or diffuse cortical lesions and has a poor prognosis (see Iragui and McCutchen). An even less common EEG abnormality is “spindle coma,” in which sleep spindles dominate the record (see “Disorders of Sleep Related to Neurologic Disease” in Chap. 18). The EEG may also demonstrate continuous seizure activity (non-convulsive status), making it valuable in the diagnosis of unresponsive states of obscure cause.


Neurology_Adams

Neurology_Adams. Our current understanding of the anatomy and physiology of alertness comes largely from the elegant experiments of Bremer and of Moruzzi and Magoun in the 1930s and 1940s. Observing cats in which the brainstem had sectioned between the pons and midbrain and at the level of the lower medulla, Bremer found that the rostral section caused a sleep-like state and “synchronized” EEG rhythms that were characteristic of sleep; animals with the lower section remained awake with appropriate “desynchronized” EEG rhythms. He interpreted this to mean, in large part correctly, that a constant stream of sensory stimuli, provided by trigeminal and spinal sources, funneled through the upper brainstem was required to maintain the awake state. Subsequently, a system of “nonspecific” projections from the thalamus to all cortical regions, independent of any specific sensory nucleus, has been demonstrated. A critical refinement of this concept resulted from the observation by Moruzzi and Magoun that


Neurology_Adams

Neurology_Adams. thalamus to all cortical regions, independent of any specific sensory nucleus, has been demonstrated. A critical refinement of this concept resulted from the observation by Moruzzi and Magoun that electrical stimulation of the medial midbrain tegmentum and adjacent areas just above this level caused a lightly anesthetized animal to become suddenly alert and its EEG to change correspondingly, that is, to become “desynchronized,” in a manner identical to normal arousal by sensory stimuli. The sites at which stimulation led to arousal consisted of a series of points extending from the nonspecific medial thalamic nuclei down through the caudal midbrain. These loci were situated along a loosely organized core of neurons that anatomists refer to as the reticular system, or reticular formation.


Neurology_Adams

Neurology_Adams. The anatomic studies of the Scheibels have described widespread innervation of the reticular formation by multiple bifurcating and collateral axons of the ascending sensory systems, implying that this area is maintained in a tonically active state by ascending sensory stimulation. Because this region, especially the medial thalamus, projects widely to the cerebral hemispheres, the concept arose of a reticular activating system (RAS, or ARAS, ascending reticular activating system) that maintains the alert state and the inactivation or destruction of which led to an unarousable state. In this way, despite a number of experimental inconsistencies (see Steriade), the paramedian upper brainstem tegmentum and lower diencephalon have come to be conceived as the locus of the arousal system of the brain. The anatomic boundaries of the RAS are somewhat indistinct. The neurons of this system are interspersed throughout the paramedian regions of the upper (rostral) pontine and midbrain tegmentum;


Neurology_Adams

Neurology_Adams. brain. The anatomic boundaries of the RAS are somewhat indistinct. The neurons of this system are interspersed throughout the paramedian regions of the upper (rostral) pontine and midbrain tegmentum; at the thalamic level, the RAS includes the functionally related posterior paramedian, parafascicular, and medial portions of the centromedian and adjacent intralaminar nuclei.


Neurology_Adams

Neurology_Adams. What is more salient for clinical work is that the nuclei of the reticular formation receive collaterals from the spinothalamic and trigeminal–thalamic pathways and project not just to the sensory cortex of the parietal lobe, as do the thalamic relay nuclei for somatic sensation, but to the whole of the cerebral cortex. Thus, it would seem that sensory stimulation has a double effect—it conveys information to the brain from somatic structures and the environment and also activates those parts of the nervous system on which the maintenance of consciousness depends. The cerebral cortex not only receives impulses from the RAS but reciprocally modulates this incoming information via corticofugal projections to the reticular formation. Although the physiology of the RAS is far more complicated than this simple formulation would suggest, it nevertheless, as a working idea, retains a great deal of clinical credibility, and makes comprehensible some of the neuropathologic observations noted


Neurology_Adams

Neurology_Adams. than this simple formulation would suggest, it nevertheless, as a working idea, retains a great deal of clinical credibility, and makes comprehensible some of the neuropathologic observations noted further on, as well as the effects of deep brain stimulation to improve function in minimally conscious patients (see further on).


Neurology_Adams

Neurology_Adams. The presence of alpha rhythm with the eyes closed is a marker for wakefulness, but its representation at the cortical surface is not required for wakefulness as it is obliterated in cases of bilateral occipital infarction. It is, of course, possible that deep nuclei are still projecting the rhythm to other parts of the cerebrum and it was assumed that this maintains wakefulness but even this precept is not clear. Although for many years it has been stated that arousal causes a desynchronization of brainwave activity (in distinction to the synchronized activity of sleep), it has become apparent that during wakefulness, there also is a widespread low-voltage fast rhythm (a gamma rhythm that has a frequency of 30 to 60 Hz). This activity, coordinated by the thalamus, has been theorized to synchronize cortical activity and to account perhaps for the unification of modular aspects of experience (color, shape, motion) that are processed in different cortical regions. In this way, the rhythm


Neurology_Adams

Neurology_Adams. cortical activity and to account perhaps for the unification of modular aspects of experience (color, shape, motion) that are processed in different cortical regions. In this way, the rhythm is said to “bind” various aspects of a sensory experience or memory. This fast and widespread electrographic activity is not appreciated with the usual EEG surface recordings but it can be extracted by sophisticated mathematical transformations. Using such electrophysiologic methods, Meador and colleagues have shown that the gamma rhythm can be detected over the primary somatosensory cortex after an electrical stimulus on the contralateral hand is perceived, but not if the patient fails to perceive it. The clinical relevance of the rhythm is uncertain but it has elicited interest because it may give insight into several intriguing questions about conscious experience.


Neurology_Adams

Neurology_Adams. In the last decade, a novel perspective on consciousness has been derived from the study of functional connectivity of brain regions as reflected by functional MRI studies. At least three such interconnected networks have been detected, a salience network that has been theorized to underlie conscious perception of stimuli, a default-mode network for internal thought, and an executive-control network for externally guided awareness. Of these, Qin and colleagues found that the salience network was most closely correlated with behavioral signs of awareness but that changes in the default network corresponded to regaining consciousness after coma. These studies are interesting but at the moment only correlative and they will certainly evolve in the next decades.


Neurology_Adams

Neurology_Adams. A large number of diseases and exogenous agents interfere with the metabolic activities of the nerve cells in the cerebral cortex and the central nuclei of the brain. The better known examples are hypoxia, global ischemia, hypoglycemia, hyperand hypoosmolar states, acidosis, alkalosis, hypokalemia, hyperammonemia, hypercalcemia, hypercarbia, drug intoxication, and severe vitamin deficiencies (see Chap. 39). In general, the loss of consciousness in these conditions parallels a reduction in cerebral metabolism. For example, in the case of global ischemia, in which oxygen and glucose are removed from the brain, an acute drop in cerebral blood flow (CBF) to 25 mL/min/100 g brain tissue from its normal 55 mL/min/100 g causes slowing of the EEG and syncope or impaired consciousness; a drop in CBF below 12 to 15 mL/min/100 g causes electrocerebral silence, coma, and cessation of most neuronal metabolic and synaptic functions. Even lower levels of ischemia are tolerated if they arise more


Neurology_Adams

Neurology_Adams. CBF below 12 to 15 mL/min/100 g causes electrocerebral silence, coma, and cessation of most neuronal metabolic and synaptic functions. Even lower levels of ischemia are tolerated if they arise more slowly, but neurons cannot survive when flow is reduced below 8 to 10 mL/min/100 g. Oxygen consumption of 2 mg/min/100 g (approximately half of normal) is incompatible with an alert state. In other types of metabolic encephalopathy, cerebral blood flow may stay near normal while metabolism is greatly reduced. An exception is the coma that arises from seizures, in which metabolism and blood flow are greatly increased. Extremes of body temperature (above 41°C [105.8°F] or below 30°C [86°F]) also induce coma through a nonspecific effect on the metabolic activity of neurons. Some of these metabolic changes are probably epiphenomena, reflecting in each encephalopathy a specific type of dysfunction in neurons and their supporting cells. Again, in reference to reducing the level of consciousness,


Neurology_Adams

Neurology_Adams. changes are probably epiphenomena, reflecting in each encephalopathy a specific type of dysfunction in neurons and their supporting cells. Again, in reference to reducing the level of consciousness, for most metabolic alterations, the rate of change of the underlying derangement is as important as its absolute level.


Neurology_Adams

Neurology_Adams. The endogenous metabolic toxins that are responsible for coma in many common medical conditions cannot always be identified. In diabetes, for example, acetone bodies (acetoacetic acid, β-hydroxybutyric acid, and acetone) are present in high concentration but which causes coma is not entirely clear; similarly in uremia, there is probably an accumulation of dialyzable small molecular toxins, notably phenolic derivatives of the aromatic amino acids but these are not clearly the proximate cause of coma. In hepatic coma, elevation of blood NH3 (ammonia) to five to six times normal levels corresponds roughly to the level of coma but the direct effect on ammonia on neurons is not fully characterized. Lactic acidosis may affect the brain by lowering arterial blood pH to less than 7.0 and this alone may suffice to alter neuronal metabolism globally. The impairment of consciousness that accompanies pulmonary insufficiency is related mainly to hypercapnia. Restated, the toxic effects of these


Neurology_Adams

Neurology_Adams. may suffice to alter neuronal metabolism globally. The impairment of consciousness that accompanies pulmonary insufficiency is related mainly to hypercapnia. Restated, the toxic effects of these molecules has not been confirmed or well understood, as further on. In acute hyponatremia (Na <120 mEq/L) of whatever cause, neuronal dysfunction is probably a result of the intracellular movement of water, leading to neuronal swelling and loss of potassium chloride from the cells. The mode of action of bacterial toxins and cytokines released during the systemic inflammatory response of sepsis is likewise incompletely understood.


Neurology_Adams

Neurology_Adams. Drugs such as general anesthetics, which are addressed more fully in a later section, alcohol, opiates, barbiturates, antiepileptic drugs, antidepressants, and benzodiazepines induce coma by their direct effects on neuronal membranes in the cerebrum and RAS or on neurotransmitters and their receptors. Others, such as methyl alcohol and ethylene glycol, both act directly and by producing a metabolic acidosis. Although the coma of toxic and metabolic diseases usually evolves through stages of drowsiness, confusion, and stupor (and the reverse sequence occurs during emergence from coma), each disease imparts its own characteristic clinical features.


Neurology_Adams

Neurology_Adams. The sudden and excessive neuronal discharge that characterizes an epileptic seizure is another common mechanism of coma. Focal seizure activity has little effect on consciousness until it spreads from one side of the brain (and the body if there is a convulsion) to the other. Coma then ensues, presumably because the extension of the seizure discharge to deep central neuronal structures paralyzes their function. In other types of seizures, in which consciousness is interrupted from the very beginning, a diencephalic origin has been postulated (centrencephalic seizures of Penfield, as discussed in Chap. 15), but this idea has been contentious for decades.


Neurology_Adams

Neurology_Adams. Concussion exemplifies yet another pathophysiologic mechanism of coma. In closed head injury, it has been shown that at the moment of the concussive injury there is an transient but large increase in intracranial pressure, on the order of 200 to 700 lb/in2, lasting a few thousandths of a second. The vibration set up in the skull and transmitted to the brain was for many years thought to be the basis of the abrupt paralysis of nervous function that characterizes concussive head injury (commotio cerebri). While not excluding this mechanism, it is as likely that the sudden swirling motion of the brain induced by acceleration or deceleration from a blow to the head produces a rotation (torque) of the cerebral hemispheres around the axis of the upper brainstem. Disruption of the function of neurons in this region due to mechanical deformation is probably the proximate cause of loss of consciousness. These same physical forces, when extreme, cause multiple shearing lesions or hemorrhages in


Neurology_Adams

Neurology_Adams. in this region due to mechanical deformation is probably the proximate cause of loss of consciousness. These same physical forces, when extreme, cause multiple shearing lesions or hemorrhages in the diencephalon and upper brainstem. Chapter 34 fully discusses the subject of concussion.


Neurology_Adams

Neurology_Adams. Yet another unique form of coma is that produced by inhalation anesthetics. The effects of general anesthesia had for many years been attributed to changes in the physical chemistry of neuronal membranes. More recently, it has been recognized that interactions with ligand-gated ion channels, particularly gamma-aminobutyric acid (GABA)-A receptors and alterations in neurotransmitter function are a more likely mechanism of anesthesia-induced unconsciousness. An extensive summary of what is known about the metabolic neurochemistry of anesthetics has been given by Campagna and colleagues and by Brown and coworkers; it emphasizes the changes in neurotransmitter function rather than alterations in membrane fluidity but still do not give a unified theory of the effects of these agents, partly because different classes of drug act at different sites. Inhalation anesthetics are unusual among coma-producing drugs in respect to the sequence of inhibitory and excitatory effects that they produce


Neurology_Adams

Neurology_Adams. different classes of drug act at different sites. Inhalation anesthetics are unusual among coma-producing drugs in respect to the sequence of inhibitory and excitatory effects that they produce at different concentrations. With anesthesia, sufficient inhibition of brainstem activity can be attained to eliminate the pupillary responses and the corneal reflexes. Both return to normal by the time the patient is able to speak. Sustained clonus, exaggerated tendon reflexes, and Babinski signs are common during the process of arousal. Rosenberg and associates systematically studied these findings. Preexisting focal cerebral deficits from strokes often worsen transiently with the administration of anesthetics, as is true to a lesser extent with other sedatives, metabolic encephalopathies, and hyperthermia.


Neurology_Adams

Neurology_Adams. Aside from repeated drug overdose, recurring episodes of stupor are usually a result of the recurrence of an underlying endogenous biochemical derangement such as the hyperammonemia of hepatic failure. A similar periodic hyperammonemic coma in children and adults can come about from urea cycle enzyme defects, such as ornithine transcarbamylase deficiency. These are discussed in Chap. 36.


Neurology_Adams

Neurology_Adams. Under the title of idiopathic recurring stupor, a rare condition has been described in adult men who displayed a prolonged state of deep sleepiness lasting from hours to days intermittently over a period of many years. Despite the impression of a sleep disorder related to narcolepsy, the EEG showed widespread fast (beta) activity, and both the stupor and EEG changes were reversed by flumazenil, a benzodiazepine receptor antagonist. During the bouts, a many-fold increase of circulating endozepine-4, an ostensibly naturally occurring diazepine agonist, was present in the serum and spinal fluid. Subsequently, the authors of the original reports (Lugaresi et al) found, by the use of more advanced techniques, that intoxication with lorazepam may have accounted for at least some of the cases. Although such cases in which diazepine antagonists reverse episodes of recurrent coma continue to be reported (Huberfeld et al), the status of this entity remains ambiguous because of the difficulty in


Neurology_Adams

Neurology_Adams. such cases in which diazepine antagonists reverse episodes of recurrent coma continue to be reported (Huberfeld et al), the status of this entity remains ambiguous because of the difficulty in excluding exogenous ingestion of drugs. The vigilance-producing drug, modafinil, has also been effective in one report (Scott and Ahmed).


Neurology_Adams

Neurology_Adams. A peculiar form of transient unresponsiveness in elderly individuals has been pointed out by Haimovic and Beresford. It accounted for 2 percent of hospitalized patients referred to them for coma. The EEG and other evaluations gave no explanation but their 5 patients had various systemic illnesses. It may recur but appears to be benign. We have experience with three such patients over the years, all men in their seventh or eighth decades, who had no systemic illness and who showed no Babinski signs, pupillary abnormalities and, for the most part, eye movement limitations (one had disproportionately better horizontal than vertical gaze with oculocephalic testing). Their eyes were closed and they could be aroused briefly and inconsistently to a drowsy state. EEG showed mild diffuse slowing but without organized sleep-like activity. Patients with advanced Parkinson disease will occasionally display a similar episodic unresponsiveness but with eyes open.


Neurology_Adams

Neurology_Adams. It is unclear to us whether migraine can cause a similar syndrome of unresponsiveness, as suggested in the study of familial hemiplegic migraine by Fitzsimmons and Wolfenden. Basilar migraine may exceptionally cause transient stupor and coma. Catatonic stupor and Kleine-Levin syndrome of periodic hypersomnolence (Chap. 18) and the behavioral change of catatonia also need to be considered.


Neurology_Adams

Neurology_Adams. Coma is produced by one of two broad types of processes: The first is clearly structural, or morphologic, consisting either of a discrete structural lesion in the upper brainstem and lower diencephalon (which may be primary or secondary to compression) or of more widespread destructive changes throughout the hemispheres. The second type is metabolic or submicroscopic of the type discussed above under the topic or metabolic encephalopathy, resulting in suppression of neuronal activity in the cerebrum and reticular activating system. The clinical examination in coma is designed to separate these mechanisms and to gauge the depth or seriousness of underlying dysfunction.


Neurology_Adams

Neurology_Adams. With regard to visible structural lesions, the study of a large number of coma has disclosed 3 types of lesions, each of which directly or indirectly damage the function of the RAS or its projections to the cerebral hemispheres. In the first type, a large mass in one cerebral hemisphere is demonstrable—chiefly a tumor; abscess; massive infarct; or intracerebral, subdural, or epidural hemorrhage. These mass lesions cause coma by secondary compression of the midbrain and central thalamic region of the RAS. Either lateral displacement or direct compression of these structures by the advancing medical temporal lobe which is forced into the tentorial opening may be the proximate cause of compression (see below and also Chap. 30). Likewise, a cerebellar lesion may compress the adjacent upper brainstem reticular region by displacing it forward and upward. A detailed clinical record will show the coma to have coincided with these displacements and herniations as discussed further on.


Neurology_Adams

Neurology_Adams. In the second structural configuration, which occurs less frequently, a destructive lesion is located immediately within the thalamus or midbrain, in which case the neurons of the RAS are damaged directly. This pattern characterize supper brainstem stroke from basilar artery occlusion, thalamic and upper brainstem hemorrhages, and some forms of traumatic damage.


Neurology_Adams

Neurology_Adams. In the third type of structural damage, there is widespread bilateral damage to the cortex and cerebral white matter, the result of traumatic damage (contusions, diffuse axonal injury), bilateral ischemic strokes or hemorrhages, encephalitis, meningitis, hypoxia, or global ischemia. The coma in these cases results from interruption of thalamocortical impulses or from generalized destruction of cortical neurons. It is only if the cerebral lesions are bilateral and extensive that consciousness is impaired. Many of the diseases in this category also cause severe thalamic damage of the type mentioned earlier; contributing to coma by that mechanism.


Neurology_Adams

Neurology_Adams. Thus, the pathologic changes found in cases of coma are compatible with physiologic deductions—namely that the state of coma correlates with lesions of the diencephalic cortical-activating systems. Small and discrete lesions restricted to the upper dorsal brainstem and lower midline thalami are the smallest ones sufficient to produce coma. A study by Parvizi and Damasio, on the basis of 9 cases of restricted dorsal bilateral pontine lesions, suggested that damage at a site caudal to the midbrain RAS may also cause coma. This view expands our conceptions of the areas of the reticular system that are necessary for arousal, but further study is justified. One conceptual explanation for this configuration implicating the pons in coma would be the disruption of noradrenergic input from the locus coeruleus to the reticular system.


Neurology_Adams

Neurology_Adams. However, in the largest group of cases of coma, no structural lesion is revealed by any technique of conventional pathology. Instead, a metabolic or toxic abnormality or generalized electrical discharge (seizure) causes neuronal failure at a subcellular or molecular level. PATHOANATOMY OF BRAIN DISPLACEMENT AND HERNIATIONS (SEE ALSO CHAP. 30)


Neurology_Adams

Neurology_Adams. As pointed out above, large, destructive or space- consuming lesions of the cerebrum, such as hemorrhage, tumor, abscess, or infarction with brain swelling, usually impair consciousness indirectly by lateral and downward displacement of the subthalamic–upper brainstem structures and herniation of the medial part of the temporal lobe (uncus, hippocampus) into the opening in the tentorium. One consequence of purely lateral displacement of the midbrain, perhaps in contrast to the conventional notion of compression by herniation, is that the upper midbrain is pushed against the opposite edge of the tentorium (the Kernohan notch or, more properly, the Kernohan-Woltman phenomenon). This configuration causes weakness and a Babinski sign ipsilateral to the hemispheral lesion and later, extensor posturing on that side. The posterior cerebral artery and rarely the cisternal segment of the ipsilateral oculomotor nerve may also be compressed at the edge of the tentorium, leading to infarction of


Neurology_Adams

Neurology_Adams. on that side. The posterior cerebral artery and rarely the cisternal segment of the ipsilateral oculomotor nerve may also be compressed at the edge of the tentorium, leading to infarction of the occipital lobe in the former, and ophthalmoparesis with pupillary enlargement in the latter.


Neurology_Adams

Neurology_Adams. It follows from the foregoing discussion that unilateral destructive lesions of the hemispheres, such as infarcts or hemorrhages, do not usually cause coma unless they create some degree of mass effect, which secondarily compresses the upper brainstem. There are exceptions in which patients with massive strokes affecting the territory of the internal carotid artery are drowsy and inattentive from the onset, even before brain swelling occurs. More often they are simply apathetic with a tendency to keep their eyes closed, a state that may be misinterpreted as stupor.


Neurology_Adams

Neurology_Adams. The term herniation refers to the dislocation of a portion of the cerebral or cerebellar hemisphere from its normal position to an adjacent compartment that is bounded by dural folds, a phenomenon that is evident both at the autopsy table and by imaging of the brain. Thus, herniations are termed transfalcine (across the falx) or transtentorial (through the tentorial aperture) or are named by the structure that is displaced—cerebellar, uncal, etc. Figure 16-1 and Table 16-2 describe these displacements of brain tissue between dural compartments. Plum and Posner, following from observations by McNealy and Plum, divided the transtentorial brainstem displacements into two groups: one a central herniation syndrome with downward displacement and midline compression of the upper brainstem, and the other a unilateral insertion of the medial temporal lobe, including the uncal gyrus, into the tentorial opening and subsequent compression of the midbrain from the sides.


Neurology_Adams

Neurology_Adams. According to these authors, the central syndrome takes the form of a rostral–caudal deterioration of brainstem function: there is first apathy and drowsiness and, often, periodic Cheyne-Stokes pattern of respiration; following this, the pupils become small and react very little to light; “doll’s-head” (“doll’s-eyes,” oculocephalic) eye movements are still elicitable, as are deviations of the eyes in response to cold-water caloric testing. Bilateral Babinski signs can be detected early; later, grasp reflexes and decorticate postures appear. These signs give way to a downward gradient of brainstem signs: coma; medium-sized fixed pupils that are referable to midbrain damage; bilateral decerebrate postures; loss of vestibulo-ocular (caloric, oculovestibular) responses all of which are the result of pontine damage; irregular breathing patterns that implicate medullary destruction; and death.


Neurology_Adams

Neurology_Adams. The uncal syndrome, the result of herniation of the medial temporal lobe into the tentorial opening, differs in that drowsiness in the early stages is accompanied or preceded by unilateral pupillary dilatation, most often on the side of the mass, as a result of compression of the third nerve by the advancing uncal gyrus.


Neurology_Adams

Neurology_Adams. Our own experience does not consistently accord with this distinction between the two herniation syndromes. We have been able only occasionally to detect an orderly sequence of neural dysfunction from the diencephalic to the medullary level but this is not necessarily a contrary view to the herniation idea, only that the model is imperfect. With lateral shift and uncal herniation, one sometimes observes smallness of the pupils, rather than ipsilateral pupillary dilatation, just as drowsiness develops. Or, infrequently, the contralateral pupil may dilate before the ipsilateral one. Nor is it clear that the dilatation of one pupil is always due to compression of the oculomotor nerve by the herniated uncus. As often in pathologic material, the third nerve is stretched and angulated over the clivus or compressed under the descended posterior cerebral artery. Involvement of the third nerve nucleus or its fibers of exit within the midbrain may be responsible for the dilatation of the


Neurology_Adams

Neurology_Adams. the clivus or compressed under the descended posterior cerebral artery. Involvement of the third nerve nucleus or its fibers of exit within the midbrain may be responsible for the dilatation of the opposite pupil, the usual occurrence after the pupil on the side of the mass has become fixed (Ropper, 1990).


Neurology_Adams

Neurology_Adams. In our serial study of 12 patients with brain swelling and lateral diencephalic–mesencephalic shifts caused by hemispheral infarcts, 4 initially had no ipsilateral pupillary enlargement; in 1 patient, the pupillary enlargement was contralateral; in 3 patients, the pupils were symmetrical when drowsiness gave way to stupor or coma (Ropper and Shafran). Cyclic Cheyne-Stokes breathing was an early sign of deterioration. In one patient, the first motor sign was an ipsilateral decerebrate rigidity rather than decorticate posturing; most of the patients had bilateral Babinski signs by the time they became stuporous. The appearance of a Babinski sign on the nonhemiparetic side has been a relatively dependable but not invariant sentinel of secondary brain tissue shift at the tentorial opening.


Neurology_Adams

Neurology_Adams. The important elements of secondary compression of the upper brainstem may occur in some cases entirely above the plane of the tentorium and be due to horizontal shift of structures rather than to herniation. With acute masses, a 3to 5-mm horizontal displacement of the pineal calcification is associated with drowsiness; 5 to 8 mm, with stupor; and greater than 8 or 9 mm, with coma (Ropper, 1986). Shift of the septum pellucidum less dependably predicts the level of consciousness. The degree of vertical tissue distortion differs between cases. Pleasure and colleagues described a syndrome of low cerebrospinal fluid (CSF) pressure causing a purely downward herniation and stupor that was corrected by the infusion of fluid into the spinal canal. Others, notably Reich and colleagues, have found evidence for vertical shift to be more compelling than for horizontal displacement.


Neurology_Adams

Neurology_Adams. In any case, the location in reference to the tentorial opening, the size of a mass, and the rapidity of its expansion all determine the degree of brain distortion and displacement of crucial structures in the diencephalon and upper midbrain. Andrews and colleagues have pointed out that frontal and occipital hemorrhages are less likely to displace deep structures and to cause coma than are clots of equivalent size in the parietal or temporal lobes. Nor is it surprising that slowly enlarging masses, such as brain tumors, can cause massive displacements of brain tissue, yet result in few clinical changes. In other words, all of the above comments must take into consideration the rate of evolution of a mass and its location and relationship to vital structures that maintain arousal.


Neurology_Adams

Neurology_Adams. The neural dysfunction of deep structures, particularly of the RAS, resulting from compression is probably due to ischemia but this issue has not been well studied and it is possible that mechanical distortion of neurons or glia may contribute.


Neurology_Adams

Neurology_Adams. Many times the primary disorder underlying coma is perfectly obvious, as with severe cranial trauma or a known drug overdose. All too often, however, the comatose patient is brought to the hospital and little pertinent medical information is available. The need for efficiency in reaching a diagnosis and providing appropriate acute care demands that the physician have a methodical approach that first addresses the common and treatable causes of coma. When the comatose patient is first seen, the patient’s airway is cleared and blood pressure is restored; if trauma has occurred, one must check for bleeding from a wound or ruptured organ (e.g., spleen or liver). With hypotension, placement of a central venous line and administration of fluids and pressor agents, oxygen, blood, or glucose solutions (preferably after blood is drawn for glucose determinations and thiamine is administered) take precedence over diagnostic procedures. If respirations are shallow or labored, or if there is


Neurology_Adams

Neurology_Adams. solutions (preferably after blood is drawn for glucose determinations and thiamine is administered) take precedence over diagnostic procedures. If respirations are shallow or labored, or if there is emesis with a threat of aspiration, tracheal intubation and mechanical ventilation are instituted. An oropharyngeal airway is otherwise adequate in a comatose patient who is breathing normally. Deeply comatose patients with shallow respirations require endotracheal intubation. The patient with a head injury may also have suffered a fracture of the cervical vertebrae, in which case caution must be exercised in moving the head and neck as well as in intubation lest the spinal cord be inadvertently damaged. These matters are discussed in detail further on, under “Management of the Acutely Comatose Patient.”


Neurology_Adams

Neurology_Adams. An inquiry is then made as to the circumstances in which the person was found and their previous health, whether there was a history of diabetes, a head injury, a convulsion, alcohol or drug use, or a prior episode of coma or attempted suicide. Persons who accompany the comatose patient to the hospital should be encouraged to remain until they have been questioned. In addition to the basic laboratory tests that apply to coma, a toxicology screen is usually appropriate.


Neurology_Adams

Neurology_Adams. In assessing confusion, stupor, or coma in an already hospitalized patient, it is usually instructive to review the patient’s medications carefully. A large number of compounds may reduce alertness to the point of profound somnolence or stupor, particularly if there are underlying medical problems (e.g., a liver failure). Prominent in lists of iatrogenic drug intoxications are sedatives, antiepileptic drugs, opiates, certain antibiotics, antidepressants, and antipsychosis compounds. From an initial survey, many of the common causes of coma, such as severe head injury, alcoholism or other forms of drug intoxication, and hypertensive brain hemorrhage, are readily recognized. Following this, the basic electrolyte, glucose and renal function tests are established as a derangement of any of these may lead to stupor or coma. In certain circumstances a toxicology screen may be added, as if the patient is being seen the first time in an emergency setting.


Neurology_Adams

Neurology_Adams. Alterations in vital signs (temperature, heart rate, respiratory rate, and blood pressure) are important aids in diagnosis. Fever is most often the result of a systemic infection such as pneumonia or bacterial meningitis or viral encephalitis. An excessively high body temperature (42°C [107.6°F] or 43°C [109.4°F]) associated with dry skin should arouse suspicion of heat stroke or intoxication by a drug with anticholinergic activity. Fever should not be too easily ascribed to a brain lesion that has disturbed the temperature-regulating center, so-called central fever, which is a rare occurrence. Hypothermia is observed in patients with alcohol or barbiturate intoxication, drowning, exposure to cold, peripheral circulatory failure, advanced tuberculous meningitis, and myxedema.


Neurology_Adams

Neurology_Adams. Slow breathing points to opiate or barbiturate intoxication and occasionally to hypothyroidism, whereas deep, rapid breathing (Kussmaul respiration) should suggest the presence of pneumonia, diabetic or uremic acidosis, pulmonary edema, or the less-common occurrence of an intracranial disease that causes central neurogenic hyperventilation. Diseases that elevate intracranial pressure or damage the brain often cause slow, irregular, or cyclic Cheyne-Stokes respiration. The various disordered patterns of breathing and their clinical significance are described further on. Vomiting at the outset of sudden coma, particularly if combined with pronounced hypertension, is characteristic of cerebral hemorrhage within the hemispheres, brainstem, cerebellum, or subarachnoid spaces. Marked hypertension is observed in patients with cerebral hemorrhage and in hypertensive encephalopathy and in children with markedly elevated intracranial pressure. Hypotension is the usual finding in states of


Neurology_Adams

Neurology_Adams. is observed in patients with cerebral hemorrhage and in hypertensive encephalopathy and in children with markedly elevated intracranial pressure. Hypotension is the usual finding in states of depressed consciousness because of diabetes, alcohol or barbiturate intoxication, internal hemorrhage, myocardial infarction, dissecting aortic aneurysm, septicemia, Addison disease, or massive brain trauma. The heart rate, if exceptionally slow, suggests heart block from medications such as tricyclic antidepressants or anticonvulsants, or if combined with periodic breathing and hypertension, an increase in intracranial pressure.


Neurology_Adams

Neurology_Adams. Inspection of the skin may yield valuable information. Cyanosis of the lips and nail beds signifies inadequate oxygenation. Cherry-red coloration is typical of carbon monoxide poisoning. Multiple bruises (particularly a bruise or boggy area in the scalp), bleeding, CSF leakage from an ear or the nose, or periorbital hemorrhage greatly raises the likelihood of cranial fracture and intracranial trauma or of a severe coagulopathy causing intracranial bleeding. Telangiectases and hyperemia of the face and conjunctivae are the common stigmata of alcoholism; myxedema imparts a characteristic puffiness of the face, and hypopituitarism an equally characteristic sallow complexion. Marked pallor suggests internal hemorrhage. A macular-hemorrhagic rash indicates the possibility of meningococcal infection, staphylococcal endocarditis, typhus, or Rocky Mountain spotted fever. Excessive sweating suggests hypoglycemia or shock, and excessively dry skin, diabetic acidosis, or uremia. Large blisters,


Neurology_Adams

Neurology_Adams. staphylococcal endocarditis, typhus, or Rocky Mountain spotted fever. Excessive sweating suggests hypoglycemia or shock, and excessively dry skin, diabetic acidosis, or uremia. Large blisters, sometimes bloody, may form over pressure points such as the buttocks if the patient has been motionless for a time; this sign is particularly characteristic of the deeply unresponsive and prolonged motionless state of acute sedation, alcohol and opiate intoxication. Thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation, and diffuse fat embolism after bone injury may cause diffuse petechiae or purpura; the last of these are often aggregated in the anterior axillary folds.


Neurology_Adams

Neurology_Adams. The odor of the breath may provide a clue to the etiology of coma. Alcohol is easily recognized. The spoiled-fruit odor of diabetic ketoacidotic coma, the uriniferous odor of uremia, the musky and slightly fecal fetor of hepatic coma, and the burnt almond odor of cyanide poisoning are distinctive enough to be identified by physicians who possess a keen sense of smell. The distinctive odor of melena, experienced in the former open wards of large hospitals, is a sign of rapid gastrointestinal bleeding. Neurologic Examination of the Stuporous or Comatose Patient


Neurology_Adams

Neurology_Adams. Neurologic Examination of the Stuporous or Comatose Patient Although limited in some ways in comparison to the examination of the alert patient, the neurologic examination of the comatose patient is relatively simple. Watching the patient for a few moments often yields considerable information. The predominant postures of the limbs and body; the presence or absence of spontaneous movements on one side; the position of the head and eyes; and the rate, depth, and rhythm of respiration each give substantial information.


Neurology_Adams

Neurology_Adams. The state of responsiveness is then estimated by noting the patient’s reaction to sequentially more vigorous stimuli starting with calling his name, to simple commands, and then to noxious stimuli such as tickling the nares, supraorbital or sternal pressure, pinching the side of the neck or inner parts of the arms or thighs, or applying pressure to the knuckles. By this method, one can roughly estimate both the degree of unresponsiveness and changes from hour to hour. Vocalization may persist in stupor and will be the first response to be lost as coma appears. Grimacing and deft avoidance movements of stimulated parts of the body are preserved in stupor; their presence substantiates the integrity of corticobulbar and corticospinal tracts. Yawning and spontaneous shifting of body positions indicate a minimal degree of unresponsiveness. These signs have been elegantly summarized by Fisher based on his own observations. The widely adopted Glasgow Coma Scale, constructed originally as a


Neurology_Adams

Neurology_Adams. indicate a minimal degree of unresponsiveness. These signs have been elegantly summarized by Fisher based on his own observations. The widely adopted Glasgow Coma Scale, constructed originally as a quick and simple means of quantitating the responsiveness of patients with cerebral trauma, can be used in the grading of other acute coma-producing diseases as mentioned earlier in this chapter (see also Chap. 35). Several other scales such as the “FOUR Score” (Wijdicks et al, 2005) have been devised and are used in various units.


Neurology_Adams

Neurology_Adams. In all but the deepest stages of coma, meningeal irritation from either bacterial meningitis or subarachnoid hemorrhage will cause resistance to the initial excursion of passive flexion of the neck but not to extension, turning, or tilting of the head. Meningismus is a fairly specific but somewhat insensitive sign of meningeal irritation as commented in Chap. 1. Resistance to movement of the neck in all directions may be part of generalized muscular rigidity or dystonia or indicate disease of the cervical spine. In the infant, bulging of the anterior fontanel is at times a more reliable sign of meningitis than is a stiff neck. A temporal lobe or cerebellar herniation or decerebrate rigidity may also create resistance to passive flexion of the neck and be confused with meningeal irritation.