19
Delirium and Other Acute
The striking state in which a patient with previously
intact mentality becomes confused is observed daily on
the medical, surgical, and emergency wards of a general
hospital. Occurring, as it often does, during an infection
with fever or in the course of a toxic or metabolic disorder
(such as renal or hepatic failure) or as an effect of medica-
tion, drugs, or alcohol, it never fails to create problems
for the physician, nurses, and family. The physician has
to cope with the problem of diagnosis, often without the
advantage of a lucid history, and any program of therapy is
constantly impeded by the patient’s inattention, agitation,
sleeplessness, and inability to cooperate. Nurses are bur-
dened with the need to provide satisfactory care and a safe
environment for the patient, and at the same time, main-
tain a tranquil atmosphere for other patients. The family
must be supported as it faces the frightening prospect of a
deranged mind with peculiar behaviors and all it signifies.
These difficulties are magnified when the patient
arrives in the emergency ward, having behaved in some
irrational way, and the clinical analysis must begin with-
out knowledge of the patient’s background and underlying
medical illnesses. It is our view that such patients should
be admitted to a general medical or neurologic ward.
Transfer of the patient to a psychiatric service is under-
taken only if the behavioral disorder proves impossible to
manage on a general hospital service.
DEFINITION OF TERMS
The definition of normal and abnormal states of mind is
difficult because the terms used to describe them have
been given so many different meanings in both medical
and nonmedical writings. Compounding the difficulty is
the fact that the pathophysiology of the confusional states
and delirium is not fully understood, and the definitions
depend to some extent on their clinical causes and rela-
tionships. The following nomenclature has proved useful
and is employed in this and subsequent chapters.
Confusion is a general term denoting the patient’s
incapacity to think with customary speed, clarity, and
coherence. Its most conspicuous attributes are impaired
attention denoting reduced power of concentration,
accompanied usually by disorientation—which may be
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Confusional States
manifest or is demonstrated only by direct questioning—
inability to properly register immediate events and to recall
them later, a reduction in the amount and quality of all
mental activity, including the normally constant inner ide-
ation and sometimes, by the appearance of bewilderment.
Thinking, speech, and the performance of goal-directed
actions are less affected but are nevertheless impersistent
or abruptly arrested by the intrusion of the slightest exter-
nal stimulus. Reduced perceptiveness and accompanying
visual and auditory illusions or hallucinations are variable
features that may be appended to the picture. This is what
may be termed the global confusional state.
These disturbances appear in many contexts. The med-
ical and psychiatric literature has adopted the term delir-
ium to describe all confusional states (discussed further
on). We try to retain the term delirium to describe a special
activated state of agitation, hallucinations, and sometimes
tremulousness, which is invariably accompanied by the
confusional state. Also, as pointed out in Chap. 16 on coma,
a confusional state may appear at any stage in the evolu-
tion and resolution of a number of diseases that lead to
drowsiness, stupor, and coma—typically in the metabolic
encephalopathies but also in diseases affecting those parts
of the brain that maintain normal arousal.
Confusion is also a characteristic feature of the chronic
syndrome of dementia, where it is ultimately the product of
failure of cognition, language, memory, and other intel-
lectual functions; there it is the long-standing and pro-
gressive nature of the mental confusion that differentiates
dementia from the acute confusional and delirious states
that carry quite different implications. Finally, intense
emotional disturbances, of either manic or depressive type,
may interfere with attentiveness and coherence of thinking
and thereby produce an apparent confusional state.
Restricted forms of what could be called a type of con-
fusion appear as a result of certain focal cerebral lesions,
particularly of the frontal, parietal, and temporal lobe
association areas. Then, instead of a global inattention
and incoherence, there are specific and circumscribed
syndromes, such as unilateral neglect of self or of the
environment, inability to identify persons or objects, and
sensorimotor defects as described in Chap. 21. Yet another
special form of confusion arises as a result of disordered
language function, which also alters the stream of thought;
this aphasia is a consequence of lesions in the language
439
440 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
areas of the left temporal lobe. These are considered sepa-
rately in Chap. 22.
The many mental and behavioral aberrations that are
seen in confused patients, and their occurrence in various
combinations and clinical contexts, make it unlikely that
all forms of confusion derive from a single elementary
mental or neurobiological abnormality. While attention
is certainly near the core of confusion, and is considered
the germinal feature by some investigators, phenomena
as diverse as drowsiness and stupor, hallucinations and
delusions, disorders of perception and registration, imper-
sistence and perseveration, and so forth are not easily
reduced to one mechanism. It seems more likely that a
number of separable or overlapping disorders of function
are involved. Indeed, one view of the confusional state
that we find attractive conceptualizes confusion as a loss
of the integrative functions among all the elementary and
localizable cerebral functions such as symbolic language,
memory retrieval, and apperception (the interpretation of
primary perceptions). All of these are included under the
rubric of the confusional state, for want of a better term.
As commented, we prefer to use the term delirium to
denote a highly recognizable agitated and hypersympa-
thetic form of confusion. In addition to many of the nega-
tive elements of incoherent thinking mentioned above,
delirium defined this way is characterized by a prominent
disorder of perception; hallucinations and vivid dreams;
a kaleidoscopic array of strange and absurd fantasies and
delusions; inability to sleep; a tendency to twitch, tremble,
and convulse; and intense fear or other emotional reac-
tions. Delirium is distinguished not only by extreme inat-
tentiveness but also by a state of heightened alertness—an
increased readiness to respond to stimuli—and by over-
activity of psychomotor and autonomic nervous system
functions, sometimes striking in degree. Implicit in the
term delirium are its nonmedical connotations as well—
namely, intense agitation, or frenzied excitement, and
trembling. This distinction between delirium and other
acute confusional states is not universally accepted. Many
authors attach no particular significance to the autonomic
and psychomotor overactivity and the hallucinatory and
dream-like features of delirium, or to the underactivity
and somnolence that characterize most other confusional
states. We continue to find it useful to set delirium apart
from other nondescript confusional states, if only for
instructional purposes, because the two are manifestly
different and occur in different clinical contexts. Engel and
Romano called delirium “a state of cerebral insufficiency”
and provided one of the fullest clinical descriptions of the
syndrome and the monograph by Lipowski may be con-
sulted. Implicit in both designations is the idea of an acute,
transient, and usually relatively reversible disorder.
Impairment of memory is often included among the
symptoms of delirium and other confusional states. Reg-
istration and recall are indeed greatly reduced in the states
under discussion, but they are affected in proportion to
the degree of inattention and the inability to register new
material. The term amnesia, refers more precisely to an
isolated loss of past memories as well as to an inability to
form new ones, despite an alert state of mind and normal
attentiveness. Amnesia further presupposes an ability of
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the patient to grasp the meaning of what is going on around
him. The failure in the amnesic state is one of retention,
recall, and reproduction and must be distinguished from
states of drowsiness, acute confusion, and delirium, in
which information and events seem never to have been
adequately perceived and registered in the first place. In
both a confusional state and in amnesia, the patient is left
with a permanent gap in memory for his acute illness.
In a similar way, the term dementia (literally, an undo-
ing of the mind) denotes a deterioration of all intellectual
or cognitive functions with little or no disturbance of con-
sciousness or perception. Implied in dementia is the idea
of a gradual degradation of mental powers in a person who
formerly possessed a normal mind. Amentia, by contrast,
indicates a congenital feeblemindedness more commonly
referred to as mental retardation, or more properly, devel-
opmental cognitive delay. Dementia and amnesia are dis-
cussed more explicitly in Chap. 20.
OBSERVABLE ASPECTS OF BEHAVIOR IN
CONFUSIONAL STATES
The intellectual, emotional, and behavioral activities of
the human organism are so complex and varied that one
may question the feasibility of analyzing these activities
as reliable indicators of cerebral disease. Certainly they
do not have the same tangibility and ease of anatomic and
physiologic interpretation as sensory and motor paralysis
or aphasia. Yet one observes certain patterns of disturbed
higher cerebral function with such regularity as to make
them clinically useful in identifying a number of diseases.
Some of these disturbances gain specificity because they
are combined in ways that form clinical syndromes.
The components of mentation and behavior that
lend themselves to observation and examination are (1)
attention; (2) perception and apperception (awareness
and interpretation of sensory stimuli); (3) the capacity to
form new memories and to recall events of the recent and
distant past; (4) the ability to think and reason; (5) tem-
perament, mood, and affect; (6) initiative, impulse, and
drive; (7) social behavior; and (8) insight. Of these, the first
two are sensory, the third and fourth are cognitive, the fifth
is affective, the sixth is conative or volitional, the seventh
refers to the patient’s relationships with those around
him, and the last refers to the patient’s capacity to assess
his own functioning. Each component of behavior and
intellect has its objective side, expressed in the behavioral
responses produced by certain stimuli, and its subjective
side, expressed in the thinking and feeling described by
the patient. Less accessible to the examiner, but neverthe-
less possible to study by questioning the patient, are the
memory, planning, and other activities that continuously
occupy the mind of an alert person. They, too, are disor-
dered or quantitatively diminished by cerebral disease.
Disturbances of Attention
Critical to clear thinking is a process of maintaining
awareness of one or a limited number of external stimuli
or internal thoughts for a fixed period of time and to
 CHAPTER 19 Delirium and Other Acute Confusional States
simultaneously disregard the numerous distracting sen-
sations and ideas that constantly bombard the nervous
system. Without this ability to focus or “pay attention” and
have an “attention span,” a coherent stream of thought or
action is not possible. The undue interruption of these
activities by the intrusion of other thoughts or actions is
termed inattention, or distractibility. Two essential com-
ponents are embodied in the attention mechanism: one,
a continuous state of alertness that is normally present
throughout waking life (and underlies self-awareness); the
other, a process of selecting from the myriad sensations
and thoughts those that are relevant to the immediate situ-
ation to the exclusion of others.
The confused patient may demonstrate inattention in
almost every task undertaken. If the degree of confusion
is slight, the patient may report a difficulty with concen-
tration. If severe, there is a parallel lack of insight and
the problem is evident by easy distractibility by ambient
stimuli and by impersistence and perseveration in conver-
sation and motor tasks. Restated, attention has such a per-
vasive effect on all other aspects of mental performance
that it is often difficult to determine whether the confused
patient also has primary disorders of memory, executive,
or visuospatial function. Indeed, retentive memory may be
severely reduced in confusional states. Furthermore, the
ability to carry out a series of actions or mental operations
wherein one is required to hold in memory the result of
the previous operation (“working memory”) is intimately
tied to attention and is particularly prone to disruption in
confusional states.
The general ability to persist in a motor or mental
task emphasizes an executive side of attention, but here
one encounters a problem because the term attention has
been applied to a number of seemingly different mental
activities. One can view attention as a separate and unique
cerebral function or simply a way of referring to the persis-
tence or impersistence of any activity. We would argue that
the entire cerebrum participates in attentiveness and the
frontal and perhaps the parietal lobes are responsible for
directing its content, but that the thalamocortical system
is in a special way responsible for its raw maintenance.
Mesulam, who has written substantially about this prob-
lem, considers the frontal and parietal lobes to be at the
nexus of an “attentional matrix”; in his model, the pre-
frontal, parietal association, and limbic cortices direct and
modulate attention in an executive manner. Certainly, the
temporal lobes and other regions are involved as well.
Attention to a particular sensory modality requires
the participation of the sensory cortex, which must simul-
taneously initiate the perceptive and apperceptive pro-
cesses discussed later. What are called “modality” and
“domain-specific” attentions (e.g., face or object recogni-
tion) are more complex, and disorders of these functions
result in unique types of inattention, such as agnosia and
anosognosia (lack of recognition of a part of the body, as
discussed in Chap. 21). These are not derived from the
all-encompassing loss of attention that is part of general
confusional states but can instead be viewed as a restricted
forms of disruption of insight for which reason they are not
major components of the global confusional state.
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441
Disturbances of Perception
The process of acquiring through the senses a knowledge
of the world or, of one’s self by cohering what is sensed
into giving meaning to what is experienced, which we
have termed apperception, involves much more than being
aware of the attributes of a stimulus. New visual stimuli, for
example, activate the striate cortex and visual association
areas, wherein are probably stored the coded past repre-
sentations of these and similar classes of stimuli. Recogni-
tion involves the reactivation of this system by the same
or similar stimuli at a later time. Essential elements in the
perceptual process are the maintenance of attention, the
selective focusing on a stimulus, elimination of all extrane-
ous stimuli, and identification and naming of the stimulus
by recognizing its relationship to remembered experience.
The perception of stimuli undergoes predictable dis-
ruption in disease. Most often there is a reduction in the
number of perceptions in a given unit of time and a fail-
ure to synthesize them properly and to relate them to the
ongoing activities of the mind. Part of this, as stated above,
is due to distractibility (pertinent and irrelevant stimuli
having equal value), and inability to persist in an assigned
task. Together, these deficiencies lead to disorientation in
time and place.
Qualitative changes of perception also appear, mainly
in the form of sensory distortions, causing misinterpreta-
tions of environmental stimuli (illusions) and misidenti-
fications of persons; these, at least in part, form the basis
of hallucinatory experience in which the patient reports
and reacts to environmental stimuli that are not evident to
the examiner. There is an inability to perceive simultane-
ously all elements of a large complex of stimuli, a defect
that has been termed “failure of subjective organization.”
More specific partial losses of perception are manifest in
the “neglect syndromes.” The most dramatic examples are
observed with right parietal lesions, which render a patient
unaware of the left half of his body and the environment on
the left side. There are numerous other examples of focal
cerebral lesions that disturb or distort sensory perceptions,
each subject to neurologic testing; these are discussed
in Chap. 21. Their close connection to spatial experience
makes them understandable as alterations of appercep-
tion in the spatial-sensory sphere.
Disturbances of Memory
The retention of learned information and experiences is
involved in all mental activities. Memory may be arbitrarily
subdivided into several parts: (1) registration; (2) fixation,
mnemonic integration, and retention; (3) recognition and
recall; and (4) reproduction. As stated above, there is a
failure of learning and memory in patients with the global
confusional state as a result of impaired attention because
the material was never registered and assimilated in the
first place. In almost all circumstances, the formation of
new memories and the ability to recall old ones are dis-
turbed in tandem.
In the Korsakoff amnesic syndrome, newly presented
material appears to be correctly registered but cannot
442 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
be retained for more than a few minutes (anterograde
amnesia, or failure of learning). In this syndrome, there is
always an associated defect in the recall and reproduction
of memories that had been formed several days, weeks,
or even years before the onset of the illness (retrograde
amnesia). The fabrication of stories, called confabulation,
constitutes a third feature of the syndrome but is neither
specific nor invariably present. Intact retention with fail-
ure of recall (retrograde amnesia without anterograde
amnesia) when it is severe and extends to all events of past
life and even personal identity, is usually a manifestation
of hysteria or malingering. Certain other characteristic
defects occur in almost all memory disorders, for example,
the relative retention of older memories in preference to
newer ones (Ribot’s rule). Chapter 19 discusses this sub-
ject more fully.
Disturbances of Thinking
Thinking, the highest order of intellectual activity, remains
the most elusive of all mental operations. If by thinking
one means the selective ordering of symbols for learning,
organizing information, and problem solving, as well as
the capacity to reason and form sound judgments, then
the working units of this type of mental activity are words
and numbers. The substitution of words and numbers for
the objects for which they stand (symbolization) is a fun-
damental part of the process. These symbols are formed
into ideas or concepts, and the arrangement of new and
remembered ideas into certain orders or relationships
constitutes an intricate part of thought, presently beyond
the scope of analysis. Reference is made further on to
Luria’s analysis of the steps involved in problem solving in
connection with frontal lobe function, but actually, as he
points out, the whole cerebrum is implicated in all forms of
thinking. One may examine thinking in terms of its speed
and efficiency, ideational content, coherence and logical
relationships of ideas, and the quantity and quality of asso-
ciations to a given idea.
Aphasic disturbances are not prominent in global
confusional and delirious states, but Geschwind discussed
misnaming as an important feature among the “nonapha-
sic disorders of speech” in these conditions. Spontaneous
speech is normal, but there may be inaccuracies in rep-
etition that are most likely the result of inattention rather
than a focal cerebral lesion.
Disorders of thinking are quite prominent in the
global confusional state, in mania, dementia, and schizo-
phrenia. In confusional states of all types, the organization
of thought processes is disrupted, with fragmentation, rep-
etition, and perseveration; this is spoken of as an “incoher-
ence of thinking.” Derangements of thinking may also take
the form of a flight of ideas; patients move too facilely from
one idea to another, and their associations are numerous,
and loosely linked. This is a common feature of hypomanic
and manic states, and of some schizophrenic psychoses.
The opposite condition, poverty of ideas, is characteristic
both of depressive illnesses, in which it is combined with
gloomy thoughts, of schizophrenia, and of dementing dis-
eases, in which it is part of a reduction of all inner psychic
intellectual activity. This overall reduction in thought and
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action is the most prominent feature of diseases that dam-
age the frontal lobes.
A related condition of slowed thought, or bradyphre-
nia, is comparable to the bradykinesia of extrapyramidal
disorders. The two often coexist and the patient, for exam-
ple with Parkinson disease, can articulate that thinking is
so slow as to be virtually blocked. The content of thought
is not much altered, but it may be rendered almost use-
less when slowed to this degree. The outward manifesta-
tion of bradyphrenia is what one would expect, a delay
in response and slowness in gathering one’s thoughts to
express ideas.
Thinking may be distorted in such a way that ideas are
not checked against reality. When a false belief is main-
tained in spite of convincing evidence to the contrary,
the term delusion is used. This abnormality is common to
bipolar, schizophrenic, and paranoid states, as well as the
early stages of dementia. Often the story related by the
patient has internal logic but is patently absurd. Psychotic
patients may believe that ideas have been implanted in
their minds by some outside agency, such as the internet,
radio, television, or atomic energy; these thought control
or “passivity feelings” are characteristic of schizophrenia,
and sometimes of the psychosis of manic episodes. Also
diagnostic of some forms of schizophrenia are distortions
of logical thought, such as gaps in sequential thinking,
intrusion of irrelevant ideas, and condensation of asso-
ciations. Chapter 49 discusses these aspects of psychoses.
Although mistaken notions along the lines of delusions
do occur in the global confusional state, they change from
moment to moment and are not firmly held, quite in con-
trast to the psychotic states.
Disturbances of Emotion, Mood, and Affect
The emotional life of an individual is expressed in a vari-
ety of ways. It is widely appreciated that there are marked
individual differences in basic temperament. Throughout
their lives some persons are cheerful, gregarious, opti-
mistic, and free from worry, whereas others are just the
opposite. The state of emotionality, and changes that
are uncharacteristic to the individual lend themselves to
observation and have clinical significance. Furthermore,
some inherent personality traits may precede the develop-
ment of overt mental disease. For example, the volatile,
person is said to be liable to bipolar disease, and the sus-
picious, withdrawn, introverted person to schizophrenia
and paranoia, but there are frequent exceptions to these
statements.
Strong, persistent emotional states, such as fear and
anxiety, may occur as reactions to life situations and are
accompanied by numerous derangements of visceral func-
tion. If excessive, prolonged, and disproportionate to the
stimulus, they are usually manifestations of an anxiety state
or depression. In depression, almost all stimuli also tend
to enhance the somber mood of unhappiness. Affective
displays that are excessively labile and poorly controlled or
uninhibited are a common manifestation of many cerebral
diseases, particularly those involving the corticopontine
and corticobulbar pathways. This disorder constitutes part
of the syndrome of spastic bulbar (pseudobulbar) palsy,
 CHAPTER 19 Delirium and Other Acute Confusional States
as discussed in Chaps. 22 and 24, but it may occur indepen-
dently of any problem with brainstem function. Conversely,
all emotional feeling and expression may be lacking, as in
states of profound apathy or depression. Or excessive cheer-
fulness may be maintained in the face of serious, potentially
fatal disease or other adversity—a pathologic euphoria.
Finally, a patient’s emotional responses may be inappropri-
ate to the stimulus, for example, a depressing or morbid
thought may seem amusing and be attended by a smile, a
bizarre affective state as in schizophrenia.
Temperament, mood, and other emotional experi-
ences are evaluated by observing the patient’s behavior
and appearance while questioning him about his feelings.
For these purposes, it is convenient to divide emotional-
ity into mood and affect. By mood is meant the prevailing
internal emotional state of an individual. By contrast,
affect (or feeling) refers to the outward emotional reactions
evoked by a thought or an environmental stimulus. As
such, it is the observable aspect of emotion. The patient’s
language (e.g., the adjectives used), facial expression, atti-
tude, posture, and speed of movement reflect prevailing
mood. These distinctions are at times rather tenuous, but
they are clinically valuable because pathologic processes
may dissociate the two to an extreme degree.
Disturbances of Impulse (Conation) and Activity
Reference was made in Chaps. 3 and 4 to weakness, aki-
nesia, and bradykinesia as manifestations of corticospinal
and extrapyramidal disease. Disorders of these parts of
the motor system interfere with voluntary or automatic
movements, much to the distress of the patient. But motil-
ity and activity can be impaired in more general ways in
which the overall tone of the motor system is enhanced
or diminished. One such disorder is a lack of conation, or
impulse. These terms emphasize that the basic biologic
urges, driving forces, or purposes by which every organ-
ism is motivated to achieve an endless series of objectives.
Indeed, motor activity is ostensibly a necessary and sat-
isfying objective in itself, for few individuals can remain
still for long before they become fidgety or doodle, and the
severely retarded apparently obtain gratification from cer-
tain rhythmic movements, such as rocking, head banging,
and hand flapping. These are all presumed to be driven by
mental impulses. As discussed in Chap. 4, tics and com-
pulsions apparently also represent the fulfillment of some
psychic urge.
However, in reference to the confusional states, a
quantitative reduction in all spontaneous activity, that is,
in the amount of activity per unit of time, is one of the most
frequent manifestations of cerebral disease. An important
aspect of this state, called abulia, is a prominent delay in
producing movement, speech, ideation, and emotional
reaction, together observed as a kind of apathy. The terms
bradyphrenia, and “psychomotor retardation,” referred
to above may be a related or perhaps identical phenom-
ena. With certain cerebral diseases the disinclination to
move and act may reach an extreme degree, to a point
where a person who is wide awake and perceptive of the
environment does not speak or move for weeks on end
(akinetic mutism). Such patients seem indifferent to what
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443
is happening around them, and unconcerned about the
consequences of their inactivity.
Abulia and akinetic mutism must be distinguished
from catatonia. Kahlbaum, who first used the term catato-
nia in 1874, described it as a condition in which the patient
sits or lies silent and motionless, with a staring counte-
nance, completely without volition and without reaction
to sensory impressions. Sometimes there is resistance to
the examiner’s efforts to move the patient, or the patient
repeats certain movements or phrases hour after hour. If
the limbs are moved passively, they may retain their new
position for a prolonged period (flexibilitas cerea, or “waxy
flexibility”), but more often there is no actual motor rigid-
ity except that of voluntary resistance, termed paratonia.
Profound depression or other psychosis is the usual cause
of catatonia. The psychomotor retardation of psychosis
may be so profound that the patient makes no attempt to
help himself in any way and ultimately starves unless fed
with a nasogastric tube.
Less easy to understand is a form of “lethal catatonia,”
originally described by Stauder, in which the completely
inert catatonic patient develops a high fever, collapses, and
dies. In some respects, this state resembles the neuroleptic
malignant syndrome, an idiosyncratic consequence of
intoxication with neuroleptic drugs. In abulia, catatonia,
and depression, the mind is usually sufficiently alert to
record events and later to recount them, which differenti-
ates these states from stupor and the vegetative state. But
these distinctions are not always valid, for there are cata-
tonic schizophrenic and depressive patients who could not
recall what had happened during the period of illness.
Pathologic degrees of motor or mental restlessness and
hyperactivity, seen characteristically in delirium tremens,
represent the opposite extreme from abulia. Akathisia refers
to constant restless movements and inability to sit still; in
some patients, this is a consequence of the prolonged use
of phenothiazines, butyrophenones, newer antipsychosis
drugs, and l-dopa, but it is also seen in a major feature of
agitated depressions. Hyperactivity-inattention disorders
describe yet another form of excessive motor activity that
usually accompanies an attention deficit syndrome of
children, mostly boys (attention-deficit hyperactivity dis-
order [ADHD]). In the manic form of bipolar disease (and
to a lesser extent in hypomania), continuous activity and
insomnia are added to the flight of ideas and the euphoric
(although somewhat irritable) mood. Following certain
cerebral diseases, notably some forms of encephalitis and
during recovery from traumatic lesions of the frontal lobes,
the patient may remain in a state of constant uncontrol-
lable and sometimes destructive activity. Kahn referred to
this state as “organic drivenness.”
Disorders of Social Behavior
Behavioral disturbances are common manifestations of all
delirious–confusional states, particularly those of toxic–
metabolic origin, but also those caused by more obvious
structural disease of the brain. The patient may be com-
pletely indifferent to all persons around him, or the oppo-
site, when any approach may excite anger and aggressive
action. Family members may be treated with disrespect,
444 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
regarded with suspicion, or falsely accused of harming the
patient, stealing his possessions, or trying to poison him.
The embarrassment consequent to urinating in public or
soiling the bed may be absent and, particularly in men,
there may be lewd behavior toward the opposite sex. In
its most extreme form, usually seen in the later stages of
dementing diseases, irascible behavior degenerates to
kicking, screaming, biting, spitting, and an aversion to
being touched, making it entirely impossible to approach
the patient. These aspects of disordered mental function
are the most alarming to the family and are difficult to
manage in the hospital. Previously upstanding, socially
appropriate, and abstemious persons may lose all regard
for their actions and become profligate, gamblers, or
alcoholics. In cases of damage to the frontal lobes, even
beyond a neglect for social conventions, there can be an
indifference to others and to the consequences of the
patient’s actions on other members of society.
In contrast, docility and amiable social behavior char-
acterize certain conditions such as Down and Williams
syndromes, and social indifference and a lack of ability to
interpret the emotional state of others are major features of
autism (see “Delirium” later on).
Loss of Insight
The state of being aware of the nature and degree of
one’s deficits and their consequences becomes manifestly
impaired or abolished in relation to many cerebral dis-
eases, not just those of the frontal lobes. It is common in all
but the mildest confusional states. This is reflected by the
observation that patients with confusional or dementing
states rarely seek advice or help for their illnesses; instead,
the family usually brings the patient to the physician or
some behavioral anomaly causes police or social services
to refer the patients to medical care. And, after the diagno-
sis has been made, the loss of insight may be reflected in
a lack of compliance with planned therapy. It is apparent
that diseases that produce abnormalities of insight also
reduce the patient’s capacity to make accurate introspec-
tions concerning his psychic function.
Lack of insight is a far more complex phenomenon
than the operational definition given above suggests. In
particular, there are many restricted forms of unaware-
ness of gross neurologic deficits. These are the agnosias,
discussed in Chap. 21.
SYNDROMES OF CONFUSION
To summarize, the entire group of acute confusional
and delirious states is characterized principally by an
alteration of consciousness and by prominent disorders
of attention and perception, which interfere with the
speed, clarity, and coherence of thinking, the formation
of memories, and the capacity for performance of self-
directed and commanded activities. Three major clinical
syndromes can be recognized. One is an acute confusional
state in which there is manifest reduction in alertness
and psychomotor activity. A second syndrome, alluded
to as a special form of confusion, delirium, is marked by
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overactivity, sleeplessness, tremulousness, and promi-
nence of vivid hallucinations, sometimes with excessive
sympathetic activity. These two illnesses tend to develop
acutely, to have multiple causes and, except for a few cere-
bral diseases, to remit within a relatively short period of
time of days to weeks, leaving the patient without residual
damage. The third syndrome is one in which a confusional
state occurs in persons with an underlying chronic cere-
bral disease, particularly a dementia. Dr. Raymond Adams
designated this frequently encountered disposition to a
superimposed acute confusional state in the context of
dementia as a beclouded dementia but the term, while apt,
seems not to have caught on.
From the neurologic perspective, the generic term
psychosis applies to states of confusion in which elements
of hallucinations, delusions, and disordered thinking com-
prise the prominent features. An important point to be
made here is that psychoses typically leave the sensorium
relatively unclouded and allow for normal attentions and
high-level performance of many mental tasks. These syn-
dromes and some aspects of psychotic confusion are
elaborated below.
Characteristically, the confusional states fluctuate in
severity, typically being worse at night (“sundowning”).
In the mildest form, the patient appears alert and may
even pass for normal; only the failure to recollect and
accurately reproduce happenings of the past few hours or
days reveals the subtle inadequacy of his mental function.
The more obviously confused patient spends much of his
time in idleness, and what he does may be inappropriate
and annoying to others. Only the more automatic acts and
verbal responses are performed properly, but these may
permit the examiner to obtain a number of relevant replies
to questions about age, occupation, and residence. Orien-
tation to the date, day of the week, and place is imprecise,
often with the date being off by several days, the year being
given as several years or one decade previous, or with the
last two numbers transposed, for example, 2015 given as
2051. Such patients may, before answering, repeat every
question that is put to them, and their responses tend to
be brief and mechanical. It is difficult or impossible for
them to sustain a conversation. Their attention wanders
and they constantly have to be brought back to the subject
at hand. They may even fall asleep during the interview,
and if left alone are observed to sleep more hours each day
than is natural or to sleep at irregular intervals.
As the confusion deepens, conversation becomes
more difficult, and at a certain stage these patients no
longer notice or respond too much of what is happening
around them. Questions may be answered with a single
word or a short phrase, spoken in a soft tremulous voice or
whisper, or the patient may be mute. Asterixis is a common
feature if a metabolic or toxic encephalopathy is respon-
sible for the confusional state. In the most advanced stages
of the illness, confusion gives way to stupor and, finally, to
coma (see Chap. 16). With improvement in the underly-
ing condition, they may pass again through the stages of
stupor and confusion in the reverse order. All this informs
us that at least one category of confusion is but a manifes-
tation of the same disease processes that affect awakeness
and alertness and, in their severest form, cause coma.
 CHAPTER 19 Delirium and Other Acute Confusional States 445

Table 19-1
CLASSIFICATION OF CONFUSIONAL STATES
I. Acute global confusion with psychomotor underactivity
A. Associated with a medical or surgical disease (no focal or lateralizing neurologic signs; imaging and cerebrospinal fluid [CSF]
normal)
1. Metabolic disorders (hepatic stupor, uremia, hypo- and hypernatremia, hypercalcemia, hypo- and hyperglycemia, hypoxia,
hypercapnia, porphyria, and some endocrinopathies including steroid-responsive Hashimoto encephalopathy)
2. Infectious illnesses (pneumonia, endocarditis, urosepsis, peritonitis, and other illnesses causing bacteremia and sepsis—septic
encephalopathy)
3. Congestive heart failure or pulmonary failure
4. Postoperative and posttraumatic states
B. Associated with drug and medication effects or intoxication (no focal or lateralizing signs; brain imaging and CSF normal): opiates,
anticholinergics, sedatives, trihexyphenidyl, corticosteroids, high-potency cannabinoids, anticonvulsants, L-dopa, dopaminergic
agonists, serotonergic antidepressants, certain antibiotics and cancer chemotherapies
C. Associated with diseases of the nervous system (with focal or lateralizing neurologic signs or CSF changes)
1. Cerebrovascular disease, tumor, abscess (especially of the right parietal, left temporal and occipital, and inferofrontal lobes)
2. Subdural hematoma
3. Meningitis
4. Encephalitis
5. Cerebral vasculitis (e.g., granulomatous, lupus)
6. Hypertensive encephalopathy, toxemia of pregnancy
7. Nonconvulsive status epilepticus and postseizure state
II. Delirium with motor, mental, or autonomic hyperactivity
A. In a medical or surgical illness (no focal or lateralizing neurologic signs; CSF usually clear): pneumonia, sepsis and bacteremia
(septic encephalopathy), postoperative period(especially cardiac surgery), postconcussive states, thyrotoxicosis and corticosteroid
excess (exogenous or endogenous), certain special infectious fevers such as typhoid and malaria
B. In neurologic disease that causes focal or lateralizing signs or changes in the CSF
1. Confusional states caused by focal cerebral lesions (see Chap. 21); vascular, neoplastic, or other diseases, particularly those
involving the temporal lobes and upper part of the brainstem
2. Concussion and contusion (posttraumatic delirium)
3. Meningitis of acute purulent, fungal, tuberculous, and neoplastic types (Chap. 31)
4. Encephalitis from viral (e.g., herpes simplex, infectious mononucleosis), bacterial (mycoplasma, legionnaires), and other causes
(Chaps. 30 and 31)
5. Acute disseminated encephalomyelitis (ADEM)
6. Auto-antibody disorders (anti-NMDA, paraneoplastic limbic encephalitis; Hashimoto encephalopathy)
7. Subarachnoid hemorrhage
C. Abstinence/withdrawal states, especially withdrawal of alcohol (delirium tremens) or of sedative drugs following chronic use
III. Psychosis, particularly with manic features
IV. Dementia or other brain disease in combination with infectious fevers, medication reactions, trauma, heart failure, or other medical or
surgical diseases

Etiology
Table 19-1 lists some of the many causes of the common
type of global confusional state. The most frequent in
general practice are drug intoxications and endogenous
metabolic encephalopathies, mainly electrolyte and water
imbalance (hypo- and hypernatremia, hyperosmolarity),
hypercalcemia, disorders of acid–base balance, renal and
hepatic failure, hyper- and hypoglycemia, febrile and sep-
tic states (“septic encephalopathy” discussed further on),
and chronic cardiac and pulmonary insufficiency.
Diffuse or multifocal disease of the cerebral hemi-
spheres is another class of transient or persisting confu-
sional states. Concussion and seizures, especially petit
mal or temporal lobe status epilepticus or the postictal
state, and certain focal (e.g., right parietal and tempo-
ral) cerebral lesions may also be followed by a period of
confusion. Focal lesions, most often infarctions but also
hemorrhages, of the right cerebral hemisphere may evoke
an acute confusional state. Such syndromes have been
described with strokes mainly in the territory of the right
middle cerebral artery (Mesulam et al; Caplan et al; Mori
and Yamadori); usually the infarcts have involved the pos-
terior parietal lobe or inferior frontostriatal regions, but
they have also occurred with strokes in the territory of one
posterior cerebral artery. A variety of more generalized
or multifocal cerebral diseases may be associated with
transient or persistent confusional states. Among these are
meningitis, encephalitis, thrombotic thrombocytopenic
purpura (TTP), disseminated intravascular coagulation,
tumors, subdural hematoma, and cranial trauma.
A more restricted group of focal cerebral diseases,
including drug and alcohol withdrawal and systemic infec-
tions cause delirium, as discussed below.
Pathophysiology of Confusional States
All that has been said on this subject in Chap. 16 regard-
ing coma is applicable to at least one subgroup of the
confusional states. In most cases, no consistent pathologic
change is found because the abnormalities are metabolic
and subcellular. As discussed in Chap. 2, the electroen-
cephalogram (EEG) is almost invariably abnormal in even
mild forms of this syndrome, in contrast to delirium tre-
mens, where the changes may be relatively minor. Bilateral
high-voltage slow waves in the range of 2 to 4 per second
(delta) or 5 to 7 per second (theta) are the usual findings
with confusion. These changes surely reflect one aspect of

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446 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
the central problem—the diffuse impairment of the cere-
bral mechanisms governing alertness and attention and
the property of coherence imparted by these functions.
If only theoretically, mental incoherence and the disor-
ganized thinking and behavior of the confusional states
reflect the loss of integrated activity of all of the associative
regions of the cortex as mentioned earlier in the chapter.
Delirium
This is best depicted in the patient undergoing withdrawal
from alcohol after a sustained period of intoxication, that
is, delirium tremens. The symptoms usually develop over
a period of 2 or 3 days. The first indications are difficulty in
concentration, restless irritability, increasing tremulous-
ness, and insomnia. There may be momentary disorien-
tation, an occasional inappropriate remark, or transient
illusions or hallucinations.
These initial symptoms rapidly give way to a clinical
picture that is one of the most colorful in medicine. The
patient is inattentive and unable to perceive the elements
of his situation. He may talk incessantly and incoherently,
and look distressed and perplexed; his expression may
be in keeping with vague notions of being annoyed or
threatened by someone. From his manner and the content
of speech, it is evident that he misinterprets the meaning
of ordinary objects and sounds, misidentifies the people
around him, and is experiencing vivid visual, auditory, and
tactile hallucinations, often of a most unpleasant type. At
first the patient can be brought into touch with reality and
may identify the examiner and answer other questions
correctly; but almost at once he relapses into a preoccu-
pied, confused state, giving incorrect answers and being
unable to think coherently. As the process evolves, the
patient cannot shake off his hallucinations and is unable to
make meaningful responses to the simplest questions and
is profoundly distracted and disoriented. Sleep is impos-
sible or occurs only in brief naps. Speech is reduced to
unintelligible muttering.
The signs of overactivity of the autonomic nervous
system, more than any others, distinguish delirium from
other confusional states. Tremor of fast frequency and
jerky restless movements are practically always present
and may be of high amplitude. The face is flushed, the
pupils are dilated, and the conjunctivae are injected; the
pulse is rapid, blood pressure elevated, and the tempera-
ture may be raised. There is excessive sweating. Most of
these signs are reflections of overactivity of the sympa-
thetic nervous system.
The most certain indication of the subsidence of the
attack is the occurrence of lucid intervals of increasing
length and sound sleep. Recovery is usually complete. In
retrospect, the patient has only a few vague memories of
his illness or none at all. Single seizures may punctuate the
syndrome at any time, including before its development.
Fragments of the full syndrome are common. Brief
disorientation, isolated hallucinations, or restlessness with
mild hypersympathetic features all occur in withdrawal
states from sedative medications, febrile illnesses, and
with various intoxications as well as with the syndrome
associated with antibodies to the NMDA receptor of the
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type associated with ovarian teratoma, with overdosage
from sympathetic drugs such as the selective serotonin
reuptake inhibitors or those with atropinic effects (see
below), and from ingestion of psychoactive substances
such as phencyclidine (PCP). Delirium may also occur
in association with a number of recognizable cerebral
diseases, such as viral (herpes) encephalitis or meningo-
encephalitis, cerebral trauma, cerebral hemorrhage after
surgery for craniopharyngioma or other tumors in the
same region, or multiple embolic strokes caused by sub-
acute bacterial endocarditis, cholesterol or fat embolism,
or following cardiac or other surgery.
The brains of patients who have died in delirium
tremens from alcohol withdrawal without associated dis-
ease or injury usually show no pathologic changes of
significance. The topography of the lesions in most of the
deliriums that are symptomatic of underlying destructive
processes is of interest; they tend to be localized in the
rostral midbrain and hypothalamus or in the temporal
lobes, where they involve the reticular activating and lim-
bic systems. Involvement of the hypothalamus perhaps
accounts for the autonomic hyperactivity that character-
izes delirium in some cases of cerebral disease and the
autoantibody condition. That these are not the only sites
implicated is emphasized by the observations that an
acute agitated delirium has occurred, albeit infrequently,
with lesions involving the fusiform and lingual gyri and the
calcarine cortex (Horenstein et al); the hippocampal and
lingual gyri (Medina et al); or the middle temporal gyrus
(Mori and Yamadori).
Electrical stimulation studies of the human cerebral
cortex during surgical exploration and studies by positron
emission tomography (PET) have emphasized the impor-
tance of the temporal lobe in the genesis of complex visual,
auditory, and olfactory hallucinations. Subthalamic and
midbrain lesions may give rise to visual hallucinations that
are not unpleasant and are accompanied by good insight
(“peduncular hallucinosis” of Lhermitte). For reasons not
easily explained, with pontine-midbrain lesions, there
may be unformed auditory hallucinations.
The EEG in delirium may show symmetrical mild gen-
eralized slow activity in the range of 5 to 10 per second. In
milder degrees of delirium, there is usually no abnormal-
ity at all; this is in stark contrast to the generalized slowing
and disruption of EEG activity that accompany most other
forms of confusion in proportion to the severity of the
clinical state.
Analysis of the conditions conducive to delirium sug-
gests several physiologic mechanisms. Alcohol and seda-
tive drugs are known to have a strong depressant effect
on certain regions of the central nervous system; presum-
ably, the disinhibition and overactivity of these parts after
withdrawal of the drug are the basis of delirium. Another
mechanism is operative in the case of bacterial infec-
tions with sepsis and poisoning by certain drugs, such as
atropine and scopolamine, in which visual hallucinations
are a prominent feature. Here the delirious state probably
results from the direct action of the toxin or chemical agent
on the same parts of the brain. It has long been suggested
that some persons are much more liable to delirium than
others, but there is reason to doubt this. Many years ago,
 CHAPTER 19 Delirium and Other Acute Confusional States
Wolff and Curran showed that randomly selected persons
developed delirium if the causative mechanisms were
strongly operative. This is not surprising, for any normal
person may, under certain circumstances, experience
phenomena akin to those of delirium. A healthy person
can be induced to hallucinate by being isolated for sev-
eral days in an environment free of sensory stimulation
(sensory deprivation). A relationship of delirium to dream
states has also been postulated; both are characterized by
a loss of appreciation of time, a richness of visual imagery,
indifference to inconsistencies, and “defective reality test-
ing.” Formulations in the field of dynamic psychiatry seem
more reasonably to explain the topical content of delirium
than its occurrence. Wolff and Curran, having observed
the same content in repeated attacks of delirium from dif-
ferent causes, concluded that the content depends more
on the age, gender, intellectual endowment, occupation,
personality traits, and past experiences than on the cause
of the delirium.
Confusional States Induced by Medications
(See Also Chap. 42)
In considering the pathophysiology of confusion, it must
be again emphasized that drug intoxication—including
from drugs prescribed by physicians—is among the most
common causes in practice. The most distinctive syn-
dromes are those from drugs that have direct or indirect
anticholinergic properties. The delirium associated with
these agents is centrally mediated but may be accompa-
nied by peripheral anticholinergic manifestations. This
point is critical in the differential assessment of agitated
confusional states because other compounds, particularly
serotonergic agents used to treat depression, also can pro-
duce delirium. Thus, in addition to confusion, toxic levels
of anticholinergic compounds typically cause dry skin, dry
mouth, diminished bowel motility, and urinary hesitancy,
if not frank retention. (The clinical maxim that applies is
“red as a beet, dry as a bone, blind as a bat, hot as a hare,
and mad as a hatter.” The last part of this mnemonic has
been also attached to the dementia of mercury intoxica-
tion [see Mintzer and Burns].) By contrast, in the toxic
serotonergic syndrome associated with excessive doses of
the antidepressant drugs, salivation is normal, sweating is
increased, and the gut is hyperactive; diarrhea is common.
Moreover, the deep tendon reflexes may be exaggerated,
and there is often clonus or myoclonus as described by
Birmes and associates. Drugs with dopaminergic activity
used in the treatment of Parkinson disease are notorious
for the induction of confusion or delirium, but it appears
that the underlying disease provides an important sub-
strate. Allied compounds with sympathomimetic actions
such as cocaine and phencyclidine produce a hallucina-
tory delirium and yet others with different pharmacologic
properties such as glutaminergic activity may result in a
variety of delirious fragments or pure hallucinosis. Another
entity that arises in this context is the neuroleptic malignant
syndrome, a state associated with an agitated confusion
followed by stupor. However, the characteristic features in
neuroleptic malignant syndrome (NMS) are progressive
muscle rigidity and evidence of myonecrosis as indicated
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447
by elevations of the serum creatine kinase; usually there
is in addition some elevation of body temperature. The
clinical examination and a thorough history aid greatly in
determining which category of drug is implicated.
Dementing Disease Complicated by Confusional
States and Delirium in the Elderly
Physicians are all too familiar with the situation of an
elderly patient who enters the hospital with a medical or
surgical illness or begins a prescribed course of medica-
tion and displays a newly acquired mental confusion.
Presumably, the liability to this state is determined by pre-
existing brain disease, most often Alzheimer disease but
sometimes Parkinson disease, multiple small deep cere-
bral infarctions, or another dementing process, which may
or may not have been obvious to the family before. All the
clinical features that one observes in the acute confusional
states may be present, but their severity varies greatly.
Confusion may be reflected only in the patient’s inability
to relate the history of the illness sequentially, or it may be
so severe that the patient is virtually non compos mentis.
An analysis of other studies by Witlox and colleagues has
estimated that the risk of dementia in persons over 85 years
if an episode of global confusion has occurred is almost 9
times the rate in others of the same age. Authoritative writ-
ers have suggested that confusion is causal to subsequent
dementia but evidence for this is so far lacking.
The family and even the primary physician often
identify the problem as abrupt in onset and having no
precedent as the patient seemingly functioned well previ-
ously. However, careful questioning about the patient’s
independent capability in handling of finances and shop-
ping, organization of household matters, driving, relating
to neighbors or family, and even previous episodes of
confusion to which the family paid little heed, are usually
uncovered.
Although almost any complicating illness may bring
out a confusional state in an elderly person, the most
common are febrile infectious diseases; trauma, notably
concussive brain injuries; surgical operations, general
anesthesia and pre- and postoperative medication; even
small amounts of pain or sedative medications used for
any cause; and congestive heart failure, chronic respira-
tory disease, and severe anemia, especially pernicious
anemia. With regard to medications, those even seemingly
innocuous ones, may cause the syndrome (e.g., histamine
blockers used to reduce gastric acid, anticonvulsants, cor-
ticosteroids, and l-dopa, and certain antibiotics). Often,
a “multifactorial” etiology is implicated by physicians
and writers in this field and poor eyesight and hearing
are included in this ambiguous and unsatisfactory term,
especially when moderately severe electrolyte imbalance
or renal failure are added implicated in the mix of other
factors. Admittedly, it is difficult to determine which of
several possible factors is responsible for the patient’s con-
fusion, and often there may be more than one. In a cardiac
patient, for example, fever, hypoxia or hypercarbia, one or
more drugs, and electrolyte imbalance each may contrib-
ute. For a perspective on the relative contributions to con-
fusion in the elderly of various medical and pharmacologic
448 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
factors, the reader may consult the review by Inouye and
colleagues.
Infectious and Postoperative Confusional States
In the instance of fever and confusion, particularly in
the elderly person, the problem of “septic encephalopa-
thy” is offered as an explanation, but it may simply be a
rephrasing of the well-known problem of infection such
as pneumonia leading to a global confusion or delirium
that was extensively discussed in the older literature by
Osler. Young has called attention to the high frequency
of this disorder in critically ill patients, 70 percent of their
bacteremic patients, and its accompaniment by a polyneu-
ropathy in a high proportion of cases. Paratonic rigidity of
the limbs (an oppositional action on the patient’s part that
is proportioned to the effort of the examiner in moving the
limbs) is an almost universal accompaniment; according
to these authors, focal cerebral or cranial nerve signs are
not encountered. All other potential causes of a confu-
sional state must, of course, be excluded before attributing
the state to an underlying infection.
The EEG is slowed in proportion to the level of con-
sciousness, but it shows mild changes even in the bactere-
mic patient who is fully alert. The spinal fluid is normal or
has a slightly elevated protein concentration. While there
is no doubt that young and healthy patients may become
confused when affected with high fever and overwhelm-
ing infections such as pneumonia, most cases of septic
encephalopathy are of the “beclouded dementia” type in
the older patient. The point made by Young is that subtle
degrees of confusion are ubiquitous with serious infec-
tions of many varieties. Among the most perplexing cases
of this type have been healthy older persons we have
observed who acquired an agitated delirium following
spinal column infection after surgery. The delirium ceased
within hours of drainage of an abscess. The older literature
contains similar examples with closed space infection in
other locations. The chapter by Young can be consulted
for an exposition of the various theories of pathogenesis of
this state. High fever itself (above 40.6°C [105°F]) is prob-
ably an adequate explanation for confusion in some cases.
A similar global confusional state occurs in patients with
severe burns (burn encephalopathy).
All that has been stated above is true of the patient
with a nondescript postoperative confusional state, in
which a number of factors, such as fever, infection, dehy-
dration, and drug and anesthetic effects, are implicated.
In a study of 1,218 postoperative patients by Moller and
colleagues, older age was by far the most important factor
associated with persistent confusion after an operation;
but a number of other factors—including the duration of
anesthesia, need for a second operation soon after the first,
postoperative infection, and respiratory complications—
were also predictive of mental difficulty in the days after
the procedure. As discussed further on, confusion appear-
ing after a surgical procedure may suggest an underlying
dementia or be predictive of the future development of
dementia. What is as important is the confusional epi-
sode may not entirely resolve for weeks or months as
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commented below. Careful questioning of the family often
reveals subtle decline is daily functioning over the prior
months or years. Unacknowledged alcoholism and with-
drawal effects undoubtedly cause the same problem quite
often on surgical services (see also “Stroke with Cardiac
Surgery” in Chap. 33).
When such patients recover from the medical or sur-
gical illness, they usually return to their premorbid state,
though their shortcomings, now drawn to the attention of
the family and physician, are far more obvious than before.
For this reason, families will date the onset of a dementia
to the time of the medical illness or surgical procedure,
and continue to minimize the previous gradual decline
in cognition. In other cases, however, the acute medi-
cal illness seemingly marks the beginning of a persistent
decline in mental clarity that over time can be identified
as a dementing illness. A related problem that has come
under study is persistent cognitive loss after critical illness.
The rates of this irreversible change are apparently high,
up to one-quarter of severely ill patients in some series,
but accurate estimates are difficult to obtain because of the
lack of pre-illness psychometric testing.
Nonconvulsive Status Epilepticus
This problem has attracted increasing attention in the
past decades as a cause of otherwise obscure confusional
states. It is discussed in Chaps. 15 and 16, but here we only
comment that the process may be portrayed clinically only
because of small myoclonic twitches or eyelid fluttering.
The only certain way to arrive at, or exclude the diagnosis
is with EEG monitoring for more than the usual 30 min
recording if possible. One suspects nonconvulsive seizures
particularly in known epileptics, septic patients, and in
certain medical diseases such as TTP.
Schizophrenic or Bipolar Psychosis During a
Medical or Surgical Illness
A small proportion of psychoses of schizophrenic or bipolar
type first become manifest during an acute medical illness
or following an operation or parturition and need to be
distinguished from an acute confusional state. The manic
state in particular can produce an overtly confusional state
but the patient sleeps little, is prone to excessive writing
and, unlike the patient with a global confusional state,
flits from one topic to the next in a vaguely pertinent way,
makes bizarre or unusual misidentifications of people,
and is reluctant to let the examiner out of the room or the
opposite, is rude and requests that the physician or an
entourage leave immediately. Rarely, a catatonic state will
make its first appearance in these circumstances. A causal
relationship between the psychosis and medical illness is
sought but cannot be established. The psychosis may have
preceded the medical illness but was not recognized. The
diagnostic study of the psychiatric illness must then pro-
ceed along the lines suggested in Chap. 48. Close observa-
tion will usually disclose a clear sensorium and relatively
intact memory, features that permit differentiation from
an acute confusional or delirious state or dementia.
 CHAPTER 19 Delirium and Other Acute Confusional States
CLASSIFICATION AND DIAGNOSIS OF ACUTE
CONFUSIONAL STATES
The syndromes themselves and their main clinical causes
are the only satisfactory basis for classification until such
time as their actual causes and pathophysiology are dis-
covered (see Table 19-1).
The first step in diagnosis is to recognize that the
patient is confused. This is obvious in most cases but, as
pointed out earlier, the mildest forms, particularly when
some other alteration of personality is prominent, may
be overlooked. Sometimes, the patient’s attention can be
best engaged by speaking softly or whispering rather than
shouting or using a conversational amplitude of voice.
A subtle disorder of orientation may be betrayed by an
incorrect response regarding dates (off by more than one
day of the month or day of the week), or in misnaming the
hospital. The ability to retain a span of digits forward (nor-
mally 7) and backward (normally 5), spelling a word such
as “world” or “earth” forward and then backward, reciting
the months of the year in their reverse order, and serial
subtraction of 3s from 30 or 7s from 100 are useful bedside
tests of the patient’s capacity for attentiveness and sus-
tained mental activity, though some of these presuppose
that the patient is literate or has a knowledge of mathemat-
ics. Another is the efficiency in performing dual tasks such
as tapping alternately with each hand while reading aloud.
Memory of recent events is one of the most delicate tests of
adequate mental function and is readily accomplished by
having the patient relate the details of entry to the hospital;
examinations undertaken in the previous days; naming
the president, vice president; and summarizing major
current events, as outlined in Chap. 21. Errors in perfor-
mance should not be minimized or attributed to age, for
they may presage serious upcoming problems during the
hospitalization.
Once it is established that the patient is confused,
the differential diagnosis must be made between an acute
confusional state associated with psychomotor underac-
tivity, delirium, a beclouded dementia, and a confusional
state that complicates focal cerebral disease. This is done
by taking into account the degree of the patient’s alert-
ness, wakefulness, psychomotor and hallucinatory activ-
ity, and disturbances of memory and impulse, as well as
the presence or absence of asterixis or myoclonus or signs
of overactivity of the autonomic nervous system and of
generalized or focal cerebral disease. In the neurologic
examination, particular attention should be given to the
presence or absence of focal neurologic signs and to
asterixis, myoclonus, and seizures.
In the chronically demented patient, there are usually
a number of “frontal release” signs, such as picking at the
bedsheets and clothes, grasping, groping, sucking, and
paratonic rigidity of the limbs. However, some demented
patients are as bewildered as those with confusional psy-
chosis, and the two conditions are distinguishable only
by differences in their mode of onset and chronicity. This
suggests that the affected parts of the nervous system may
be the same in both conditions.
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449
At times, a left hemispheral lesion causing a mild
Wernicke’s aphasia resembles a confusional state in that
the stream of speech and thought are incoherent. The
prominence of paraphasias and neologisms in spontane-
ous speech, difficulties in auditory comprehension, and
normal nonverbal behavior mark the disorder as apha-
sic in nature. However, a problem with naming may be
more common in nonaphasic global confusional states, as
alluded to earlier in the chapter and emphasized in a brief
piece by Geschwind. Spontaneous speech in these circum-
stances is unaffected.
The distinction between an acute confusional state
and dementia is difficult at times, particularly if the mode
of onset and the course of the mental decline are not
known. The patient with an acute confusional state is said
to have a “clouded sensorium” (an ambiguous term refer-
ring to a symptom complex of inattention, disorientation,
perhaps drowsiness, and an inclination to inaccurate per-
ceptions and sometimes to hallucinations and delusions),
whereas the patient with dementia usually has a clear
sensorium.
As indicated earlier, schizophrenia and bipolar psy-
chosis, particularly with mania can usually be separated
from the confusional states by the presence of a clear sen-
sorium and relatively intact memory function.
A thorough medical and neurologic examination, CT
or MRI, and—in cases with fever or with no other appar-
ent cause—blood count, chest x-ray, and lumbar puncture
should be performed. The medical, neurologic, and labo-
ratory findings (including measurements of Na, Ca, CO2,
blood urea nitrogen [BUN], NH3, calcium, glucose, Pao2,
Pco2, “toxic screen”) determine the underlying disease
and its treatment, and they also give information concern-
ing prognosis. An approach to the laboratory tests that are
useful in revealing the common conditions that give rise
to the confusional state, when the cause is not self-evident
from the history and physical examination, is given in
Table 19-2; but as always, the choice of tests is governed by
the clinical circumstances.
Table 19-2
AN APPROACH TO THE LABORATORY EVALUATION OF THE
ACUTELY CONFUSED PATIENT
I. Afebrile, no meningismus, and no focal neurologic signs
A. Endogenous metabolic disorders: glucose, sodium, cal-
cium, BUN, Pao2, Pco2, NH3, T4, and special tests in par-
ticular circumstances (for porphyria, Hashimoto thyroid
disease, etc.)
B. Exogenous toxic state: review of medications, inpatient
and outpatient, toxicologic screening of blood and urine,
history of alcohol or other drug abuse
II. Febrile or signs of meningeal irritation
A. Systemic infection: blood count, chest radiograph, urine
analysis and culture, blood cultures, erythrocyte sedimen-
tation rate
B. Meningitis and encephalitis: lumbar puncture
III. Focal neurologic signs or seizures
A. CT scan or MRI
B. EEG
450 Part 2 CARDINAL MANIFESTATIONS OF NEUROLOGIC DISEASE
CARE OF THE DELIRIOUS AND CONFUSED
PATIENT
These details are of the utmost importance. It has been
estimated that 20 to 25 percent of medically ill hospi-
tal inpatients will experience some degree of confusion;
moreover, elderly patients who are delirious have a sig-
nificant level of mortality, variously estimated at 22 to 76
percent according to Weber and colleagues. Optimal care
begins with the identification of individuals at risk for
delirium, including those who have an underlying demen-
tia, preexisting medical illnesses, or a history of alcohol-
ism or serious depression. Furthermore, delirium is more
common in males and, not surprisingly, is more likely
when sensory function is already impaired (loss of vision
and hearing) (Burns et al; Weber et al).
The primary effort is directed toward elimination of
the underlying medical problem, particularly to discon-
tinuing offending drugs or toxic agents. Other important
objectives are to quiet the agitated patient and protect him
from injury. A nurse, attendant, or member of the family
should be with a seriously confused patient if this can be
arranged. A room with adequate natural lighting will aid
in creating a diurnal rhythm of activity and reduce “sun-
downing.” It is often better to let an agitated patient walk
about the room than to restrain him in bed, which may
increase his fright or excitement and cause him to struggle
to the point of exhaustion, collapse, or self-harm. The
less-active patient can be kept in bed by side rails, wrist
restraints, or a restraining sheet or vest. Sensitive explana-
tions of these restraints to the family should be made in
terms that emphasize the patient’s health and safety. The
fully awake but mildly confused patient should be permit-
ted to sit up or walk about part of the day unless the pri-
mary disease contraindicates this.
All drugs that could possibly be responsible for the
acute confusional state or delirium should be discontin-
ued if this can be done safely. These include sedating,
antianxiety, narcotic, anticholinergic, antispasticity, and
corticosteroid medications, l-dopa, metoclopramide, and
cimetidine, as well as antidepressants, antiarrhythmics,
antiepileptics, and antibiotics. Despite the need to be spar-
ing with medications in these circumstances, haloperidol,
quetiapine, and risperidone are helpful in calming the
severely agitated and hallucinating patient, but they too
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Caplan LR, Kelly M, Kase CS, et al: Mirror image of Wernicke’s
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Engel GL, Romano J: Delirium: a syndrome of cerebral insuffi-
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Geschwind N: Non-aphasic disorders of speech. Int J Neurol
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should be used in the lowest effective doses. An exception
is alcohol or sedative withdrawal, in which chlordiazepox-
ide or other diazepines are favored by most physicians (see
Chap. 41). In delirious patients, the purpose of sedation is
to assure rest and sleep, avoid exhaustion, and facilitate
nursing care, but one must be cautious in attempting
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known in the past to be effective in quieting the delirious
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and delirious patients recover if they receive competent
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