Diagnosis of delirium and confusional states

Authors:
Joseph Francis, Jr, MD, MPH
G Bryan Young, MD, FRCPC
Section Editors:
Michael J Aminoff, MD, DSc
Kenneth E Schmader, MD
Deputy Editor:
Janet L Wilterdink, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2017. | This topic last updated: Aug 22, 2014.

INTRODUCTION Delirium and confusional states are among the most common mental disorders
encountered in patients with medical illness, particularly among those who are older. They are associated with
many complex underlying medical conditions and can be hard to recognize. Systematic studies and clinical
trials are difficult to perform in patients with cognitive impairment. Recommendations for evaluating and
treating delirium are based primarily upon clinical observation and expert opinion [1].

Knowledge of the clinical epidemiology of delirium and confusional states in various settings has substantially
increased as a result of applying standardized diagnostic methods. These prospective observational studies
provide a basis for understanding and managing the disorder.

The epidemiology, pathogenesis, clinical features, and diagnosis of delirium and confusional states will be
reviewed here. The prevention and treatment of these disorders are discussed separately. (See "Delirium and
acute confusional states: Prevention, treatment, and prognosis".)

DEFINITION AND TERMINOLOGY The American Psychiatric Association's Diagnostic and Statistical
Manual, 5th edition (DSM-V) lists five key features that characterize delirium [2]:

Disturbance in attention (reduced ability to direct, focus, sustain, and shift attention) and awareness.
The disturbance develops over a short period of time (usually hours to days), represents a change from
baseline, and tends to fluctuate during the course of the day.
An additional disturbance in cognition (memory deficit, disorientation, language, visuospatial ability, or
perception)
The disturbances are not better explained by another preexisting, evolving or established neurocognitive
disorder, and do not occur in the context of a severely reduced level of arousal, such as coma
There is evidence from the history, physical examination, or laboratory findings that the disturbance is
caused by a medical condition, substance intoxication or withdrawal, or medication side effect.

Additional features that may accompany delirium and confusion include the following:

Psychomotor behavioral disturbances such as hypoactivity, hyperactivity with increased sympathetic

activity, and impairment in sleep duration and architecture.
Variable emotional disturbances, including fear, depression, euphoria, or perplexity.

There is no generally accepted consensus regarding the distinction between delirium and confusional states.
The terms "acute confusional state" and "encephalopathy" are often used synonymously with delirium. The
more general term "confusion" is used to indicate a problem with coherent thinking. Confused patients are
unable to think with normal speed, clarity, or coherence [3]. Confusion is typically associated with a depressed
sensorium and a reduced attention span, and it is an essential component of delirium.

The term "acute confusional state" refers to an acute state of altered consciousness characterized by
disordered attention along with diminished speed, clarity, and coherence of thought [3]. Although this definition
encompasses delirium as well, some experts use "confusional state" to convey the additional meaning of
reduced alertness and altered psychomotor activity [3]. In this paradigm, delirium is a special type of
confusional state characterized by increased vigilance, with psychomotor and autonomic overactivity; the
delirious patient displays agitation, excitement, tremulousness, hallucinations, fantasies, and delusions.

In this discussion, the term delirium will be used in the sense of the DSM-V definition. The additional
components of agitation, tremor, and hallucinations are allowed for but are not essential diagnostic features of
delirium in the DSM-V usage. Confusion and other states of altered consciousness are encompassed by the
DSM-V definition of delirium.

EPIDEMIOLOGY Delirium and confusion have primarily been studied in hospital settings. Nearly 30 percent
of older medical patients experience delirium at some time during hospitalization [4,5]. Among older surgical
patients, the risk for delirium varies from 10 to greater than 50 percent; the higher figures are associated either
with frail patients (eg, those who have fallen and sustained a hip fracture) or complex procedures such as
cardiac surgery [6].

In general, delirium can be found wherever there are sick patients. When standardized screening and
diagnostic tools (see 'Evaluation' below) have been applied prospectively to consecutive patients, high rates of
delirium have been demonstrated in intensive care units (70 percent) [7], emergency departments (10 percent)
[8], hospice units (42 percent) [9], and postacute care settings (16 percent) [10]. Now that the care of sicker
patients has become fragmented across a variety of venues, clinicians are challenged to identify and manage
delirium efficiently across a wide variety of settings.

PATHOGENESIS The pathophysiology of delirium and confusion is poorly understood. Most theories are
overly simplified. With so many disparate etiologies (table 1), it is highly unlikely that a single mechanism is
universally operative.

The biologic basis of delirium and confusion is poorly understood in part because it is difficult to study severely
ill patients with conventional electrophysiologic tests, brain imaging, or neurotransmitter assays. Rarely can the
observed phenomena attributed to delirium be separated reliably from that of underlying illness and drug
treatment. Animal models for delirium have been proposed but are in their infancy and still not validated.

Despite these limitations, some important data regarding the pathophysiology of delirium have been reported.
Risk factors for the development of delirium have also been identified.

Neurobiology of attention Since a disorder of attention is a universal feature of confusional states, it helps
to understand the neurobiology of attention.

Arousal and attention may be disrupted by brain lesions involving the ascending reticular activating
system (ARAS) from the mid-pontine tegmentum rostrally to the anterior cingulate regions.
Attention in both right and left aspects of extrapersonal space is governed by the "nondominant" parietal
and frontal lobes. Thus with inattention, there is typically some disruption of the integrated function of
these regions.
Insight and judgment are dependent on intact higher order integrated cortical function. Since insight into
perceptions is often reduced with delirium and confusional states, it seems likely that higher order cortical
 function is therefore impaired, especially regarding frontal lobe involvement in scrutinizing incoming
sensory information.

Cortical versus subcortical mechanisms Seminal work in the 1940s using electroencephalography
(EEG) in acutely ill patients established that delirium was a disturbance of global cortical function,
characterized by slowing of the dominant posterior alpha rhythm and the appearance of abnormal slow-wave
activity [11]. These findings correlated with the level of consciousness and other observed behaviors
regardless of the underlying etiology, suggesting a final common neural pathway. The major exception
appeared to be that of delirium accompanying alcohol and sedative drug withdrawal, in which low voltage, fast-
wave activity predominated. These findings are so consistent that EEG can be used to resolve uncertainty in
patients in whom the diagnosis of delirium is in doubt.

The results of brainstem auditory evoked potential, somatosensory evoked potentials, and neuroimaging
studies have supported an important role for subcortical (eg, thalamus, basal ganglia, and pontine reticular
formation) as well as cortical structures in the pathogenesis of delirium [12]. These findings correlate with
clinical reports that patients with subcortical strokes and basal ganglia abnormalities (including Parkinson
disease) have a higher susceptibility to delirium.

Neurotransmitter and humoral mechanisms Acetylcholine plays a key role in the pathogenesis of
delirium [13,14]. Anticholinergic drugs cause delirium when given to healthy volunteers and are even more
likely to lead to acute confusion in frail elderly persons. This effect can be reversed with cholinesterase
inhibitors such as physostigmine. (See "Anticholinergic poisoning".)

Further support for the role of acetylcholine is derived from observations that medical conditions precipitating
delirium, such as hypoxia, hypoglycemia, and thiamine deficiency, decrease acetylcholine synthesis in the
central nervous system (CNS). In addition, serum anticholinergic activity, measured with binding assays
employing purified preparations of brain muscarinic receptors, correlates with the severity of delirium in
postoperative and medical patients [13,15]. Finally, Alzheimer disease, which is characterized by a loss of
cholinergic neurons, increases the risk of delirium due to anticholinergic medications.

The anticholinergic mechanism is important for clinicians to keep in mind, since many drugs used by older
adults (including several not traditionally viewed to have "anticholinergic effects") can lead to detectable serum
anticholinergic activity measured by competitive radioreceptor binding [16,17]. Psychotropic drugs, in
particular, are likely to cause detectable serum anticholinergic activity at doses typically administered to older
patients. Some elderly patients with delirium also have elevated serum anticholinergic activity in the absence of
anticholinergic drug use, raising the possibility that endogenous anticholinergic substances may play a role in
delirium [13].

Drugs that are agonists or antagonists of a number of other neurotransmitters can produce delirium-like
effects, although the precise role of these neurotransmitter systems is difficult to determine. Cerebrospinal fluid
(CSF) studies of patients with delirium reveal alterations in neuropeptides (eg, somatostatin), endorphins,
serotonin, norepinephrine, and GABA, among others [12]. However, it is difficult to exclude the confounding
effects of underlying illness or dementia.

Pro-inflammatory cytokines such as interleukins and tumor necrosis factor alpha also may have a role in the
pathogenesis of delirium. These agents have strong CNS effects when injected into experimental animals or
when administered for therapeutic purposes (eg, interferons in chronic hepatitis). Cytokine activation may
account for delirium (particularly hyperactive forms of the disturbance) in situations such as sepsis (where
mental changes may actually precede fever), cardiopulmonary bypass [18], and acute hip fracture [19].
Risk factors Delirium is a multifactorial disorder. Factors that increase the risk for delirium and confusional
states can be classified into those that increase baseline vulnerability and those that precipitate the
disturbance [20].

The most commonly identified risk factors are underlying brain diseases such as dementia, stroke, or
Parkinson disease; these are present in nearly one-half of older patients with delirium. In a meta-analysis of
published prospective studies of delirium, the prevalence of delirium superimposed upon dementia ranged
from 22 to 89 percent [21]. Often, the dementia went unrecognized prior to the onset of delirium. Similarly, in a
study of 78 elderly patients with femoral neck fractures who were followed for five years, dementia developed
in 69 percent of the 29 patients with postoperative delirium versus only 20 percent of the 49 patients without
postoperative delirium [22].

Other factors that increase the vulnerability to delirium include advanced age and sensory impairment.

Precipitating factors Factors that may precipitate delirium are numerous and varied (table 1). Some
common examples include polypharmacy (particularly psychoactive drugs), infection, dehydration, immobility
(including restraint use), malnutrition, and the use of bladder catheters. Drugs that may precipitate delirium and
confusion are noted in the Table (table 2).

CLINICAL PRESENTATION As previously noted, several key features characterize delirium and
confusional states (see 'Definition and terminology' above) [2]. A disturbance of consciousness and altered
cognition are essential components. The condition typically develops over a short period of time and tends to
fluctuate during the course of the day. The disturbance is typically caused by a medical condition, substance
intoxication, or medication side effect. These criteria form a useful framework for understanding the clinical
presentation of the disorder.

Disturbance of consciousness One of the earliest manifestations of delirium is a change in the level of
awareness and the ability to focus, sustain, or shift attention. This loss of mental clarity is often subtle and may
precede more flagrant signs of delirium by one day or more. Thus, family members or caregivers who report
that a patient "isn't acting quite right" should be taken seriously, even if delirium is not obvious to the examining
clinician.

Distractibility, one of the hallmarks of delirium, is often evident in conversation. It is important that the examiner
be sensitive to the patient's flow of thought and not attribute tangential or disorganized speech to age,
dementia, or fatigue.

Patients will appear obviously drowsy, lethargic, or even semi-comatose in more advanced cases of delirium.
The opposite extreme, hypervigilance, may also occur in cases of alcohol or sedative drug withdrawal, but
such a presentation is less common in older persons. (See "Management of moderate and severe alcohol
withdrawal syndromes".)

Change in cognition Delirious individuals have cognitive and perceptual problems, including memory loss,
disorientation, and difficulty with language and speech. Formal mental status testing can be used to document
the degree of impairment, but more important than the test score are the patient's overall accessibility and
attentiveness while attempting to answer the questions. It is important to ascertain the patient's level of
functioning prior to the onset of delirium from family members, caregivers, or other reliable informants, since
dementia can impair cognitive ability and frequently underlies delirium.

Perceptual disturbances typically accompany delirium. Patients may misidentify the clinician or believe that
objects or shadows in the room represent a person. Vague delusions of harm often accompany these
misperceptions. Hallucinations can be visual, auditory or somatosensory, usually with lack of insight - the
patients believe they are real. Hallucinations can be simple, e.g., shadows or shapes, or complex, as people
and faces. Sounds can also consist of simple sounds or hearing voices with clear speech.

A variety of language difficulties can occur. Patients may lose the ability to write or to speak a second
language. One personal experience involved a patient who immigrated to North America as an adolescent; she
spoke only Italian during her delirium, recovering her grasp of English after her pneumonia was treated.

Temporal course Delirium develops over hours to days and typically persists for days to months. The
acuteness of the presentation is the most helpful feature in differentiating delirium from dementia. In addition,
the features of delirium are unstable, typically becoming most severe in the evening and at night. It is not
unusual for a patient with delirium to appear relatively lucid during morning rounds. Clinicians, particularly
physicians, are apt to miss the diagnosis if they rely upon only a single point assessment; evidence of the
behavior change should be actively solicited from all staff, especially those working evening and night shifts.

There is often a prodromal phase, especially in elderly patients, that later blends into quiet/hypoactive delirium
or erupts into an agitated confusional state. Prodromal features include complaints of fatigue, sleep
disturbance (excessive daytime somnolence or insomnia), depression, anxiety, restlessness, irritability and
hypersensitivity to light or sound. With progression there are perceptual disturbances and cognitive
impairment. These symptoms may fluctuate. Hypoactive delirium can, however, begin without a prodromal
phase and agitated behavior may appear as the first manifestation of delirium without a prodromal or
hypoactive phase.

Elderly patients Patients with delirium are sick by definition. However, older patients with delirium often do
not look sick apart from their behavioral change. Thus, delirium may be the only finding suggesting acute
illness in older demented patients. Caregivers must be educated that sudden changes in mental functioning
are not expected with most progressive dementias and require prompt medical attention.

Other features Delirium may present with a variety of clinical manifestations that are not essential
diagnostic features, including psychomotor agitation, sleep-wake reversals, irritability, anxiety, emotional
lability, and hypersensitivity to lights and sounds. These features are not seen in all patients with delirium and
can be evident in patients with dementia; their presence neither rules in nor rules out the diagnosis. The most
common presentation in older patients is a relatively quiet, withdrawn state that frequently is mistaken for
depression.

The relationship between clinical manifestations and outcome has not been well studied, although a report of
outcomes of delirium following hip fracture repair suggested that patients with more severe delirium, including
psychomotor agitation, had higher rates of mortality and nursing home placement [23]. Delirium that does not
resolve before discharge is also a risk factor for nursing home placement [24].

EVALUATION There are two important aspects to the diagnostic evaluation of delirium: recognizing that the
disorder is present and uncovering the underlying medical illness that has caused delirium.

Recognizing the disorder As previously mentioned, clinicians often fail to recognize delirium; in some
reports, this happens in more than 70 percent of cases. Behavioral problems or cognitive impairment may be
readily apparent but wrongly attributed to the patient's age, to dementia, or to other mental disorders. In one
study, over 40 percent of patients referred to a consulting liaison psychiatrist for the evaluation or treatment of
depression ultimately were found to have delirium [23].
Clinical confirmation The DSM-V criteria (See 'Definition and terminology' above.) form a practical
framework for assessing delirium [25]:

A change in the level of consciousness is often the first observable clue. Clinicians must not "normalize"
lethargy or somnolence by assuming that illness, sleep loss, fatigue, or anxiety are causing the changes.
In cases where the patient appears awake, the ability to focus, sustain, or shift attention can be
assessed during attempts to obtain a history; a global assessment of the patient's "accessibility" during
conversation or the performance of a mental status examination is a sensitive indicator of delirium.
Conversation with the patient may elicit memory difficulties, disorientation, or speech that is tangential,
disorganized, or incoherent. The clinician should be aware of superficially appropriate conversation that
follows social norms but is poor in content.
When in doubt, formal mental status testing should be performed, such as the Mini-Mental State
Examination or brief bedside tests of attention (table 3). Serial-sevens and spelling a word such as farm
or world backward are other simple tests of attention. (See "Evaluation of cognitive impairment and
dementia", section on 'Mini-Mental State Examination'.)

Determining that cognitive impairment or perceptual problems are not due to a prior or progressing dementia
can be challenging and requires knowledge of the patient's baseline level of functioning. The diagnosis is made
more easily if there has been a prior assessment of cognitive abilities. In other instances, informants must be
immediately sought to establish chronology. These should include formal caregivers (eg, nursing staff familiar
with the patient), family members, and informal caregivers, particularly those who may have observed
fluctuations in the patient's mental functions.

History Some historical clues to the underlying etiology of delirium and confusion can be obtained from
relatives, eg, recent febrile illness, history of organ failure, a medication list, history of alcoholism or drug
abuse, or recent depression. It is otherwise often difficult to impossible to obtain a history in the confused or
uncooperative patient. As an example, myocardial infarction may cause sufficient confusion that the patient
cannot relate a history of chest pain.

General examination A comprehensive physical examination is often difficult or impossible in the confused
or uncooperative patient. Clinicians should instead perform a focused assessment, concentrating upon vital
signs, the state of hydration, skin condition, and potential infectious foci.

The patient's general appearance may be suggestive, eg, the dusky appearance seen with chronic pulmonary
disease, the jaundiced appearance of hepatic failure, or the stigmata of renal failure. Needle tracks strongly
suggest drug abuse. Cherry-red lips indicate possible carbon monoxide poisoning. The breath may smell of
alcohol, fetor hepaticus, uremic fetor or ketones. Hyperventilation offers a limited number of possible etiologies.
(See 'Diagnostic tests' below.)

A bitten tongue or posterior fracture-dislocation of the shoulder suggests a convulsive seizure (over 40 percent
of such patients remain in nonconvulsive status epilepticus). There may also be signs of head injury.
Subhyaloid or retinal hemorrhages raise the possibility of an intracranial hemorrhage, usually from a ruptured
berry aneurysm.

Alcohol or sedative-drug withdrawal may cause a delirium characterized by autonomic nervous system
activation (tachycardia, sweating, flushing, dilated pupils) in younger persons, but these responses are blunted
or absent in the geriatric population. Anticholinergic toxicity in elders can cause delirium without peripheral
signs of atropine poisoning (eg, fever, mydriasis, tachycardia). Sepsis may present as delirium without obvious
fever (sometimes even with hypothermia) or localizing signs (eg, rebound tenderness from a perforated
viscus). (See "Evaluation of infection in the older adult".)

Pitfalls in the examination must be kept in mind: temperature may be under 38.3C (101F) even in the
presence of serious infections; auscultatory and radiographic findings of pneumonia may be subtle or absent;
and abdominal catastrophes may present without peritoneal signs in frail older patients. False-positive findings
occur as well (eg, nuchal rigidity may not signify meningitis).

Neurologic examination The neurologic examination is often confounded by inattention and altered
consciousness in patients with delirium. Certain aspects of the examination may be difficult or unreliable in
uncooperative patients (eg, sensory testing), or reflect chronic rather than acute CNS conditions. However, an
assessment emphasizing the level of consciousness, degree of attention or inattention, visual fields, and
unambiguous cranial nerve and motor deficits, is important to identify individuals with a higher likelihood of
focal neurologic disease. Posterior cortical strokes, for example, can present as delirium with few findings other
than hemianopia, and in some cases may present with no focal symptoms or signs.

The absence of focal examination findings does not exclude the possibility of focal or multifocal neurologic
lesions as the cause of the delirium. In the absence of an obvious cause for delirium, further testing including
neuroimaging, lumbar puncture, and EEG is indicated.

The physical signs of metabolic/toxic delirium can include nonrhythmic, asynchronous muscle jerking
(multifocal myoclonus), flapping motions of an outstretched, dorsiflexed hand (asterixis), and postural action
tremor. These are nonspecific findings and do not help establish any particular medical etiology within
the metabolic/toxic category. Selective loss of the vestibular-ocular reflex, or nystagmus with unexplained
ocular palsies that spare pupillary reactivity to light, raise the possibility of Wernicke's encephalopathy.

Clinical instruments The Confusion Assessment Method (CAM) is a simple tool that can be used by
clinicians to integrate their observations and identify when delirium is the most probable diagnosis (table 4). In
medical and surgical settings, the CAM has a sensitivity of 94 to 100 percent and a specificity of 90 to 95
percent [26]. The CAM has become a standard screening device in clinical studies of delirium, conducted
across multiple settings including emergency rooms and long-term care [27]. It takes five minutes to administer
and may be particularly helpful when incorporated into the routine bedside assessment. A review of 11 bedside
instruments used to identify the presence of delirium in adults concluded that the best evidence supported the
use of the CAM as the best, and the Mini Mental State Exam as the least accurate test [28].

The CAM-ICU instrument has been developed and validated for identification of delirium in the intensive care
unit (ICU) [29-31]. In mechanically ventilated patients who are unable to communicate verbally, the instrument
considers observed behaviors and nonverbal responses to simple questions, as well as visual and auditory
recognition tasks (table 4).

Another instrument, the Intensive Care Delirium Checklist for Screening (ICDSC), has also been validated in
the diagnosis of delirium in the ICU setting and had high agreement rates with the CAM-ICU in one study
[32,33].

Investigating medical etiologies Virtually any medical condition can precipitate delirium in a susceptible
person; multiple underlying conditions are often found [34]. The history and physical examination will guide
most of the investigations. The conditions noted most commonly in prospective studies of the disorder include:

Fluid and electrolyte disturbances (dehydration, hyponatremia and hypernatremia)

Infections (urinary tract, respiratory tract, skin and soft tissue)
 Drug or alcohol toxicity
Withdrawal from alcohol
Withdrawal from barbiturates, benzodiazepines, and selective serotonin reuptake inhibitors
Metabolic disorders (hypoglycemia, hypercalcemia, uremia, liver failure, thyrotoxicosis)
Low perfusion states (shock, heart failure)
Postoperative states, especially in the elderly

Less common causes that should be considered include hypoxemia, hypercarbia, Wernicke encephalopathy,
adrenal failure, primary central nervous system infection, seizures, trauma, and paraneoplastic syndromes.

A cost-effective work-up for delirium focuses upon these most likely possibilities. (See "Delirium and acute
confusional states: Prevention, treatment, and prognosis".)

Medication review Drug toxicity accounts for approximately 30 percent of all cases of delirium [16]. Thus,
the most important initial step is a medication review. The most common offenders are listed in the Table (table
2) [16]. Clinicians should be careful not to neglect over-the-counter agents, drugs prescribed by other
physicians, or drugs belonging to other household members. A simple but high-yield diagnostic procedure is to
ask a family member to clean out the medicine cabinet and bring the contents for review.

DIFFERENTIAL DIAGNOSIS Careful attention to the key features of acute onset, fluctuating course, altered
consciousness, and cognitive decline should readily distinguish delirium from depression, psychotic illness,
and dementia. When in doubt, the most useful rule-of-thumb is to assume delirium and attempt to rule out
common medical etiologies. This is true even for patients with known psychiatric illness (including dementia),
since they also are susceptible to delirium when acutely ill.

Sundowning Delirium should be distinguished from "sundowning," a frequently seen but poorly understood
phenomenon of behavioral deterioration seen in the evening hours, typically in demented, institutionalized
patients [35]. Sundowning should be presumed to be delirium when it is a new pattern. Patients with
established sundowning and no obvious medical illness may be suffering the effects of impaired circadian
regulation or nocturnal factors in the institutional environment (eg, shift changes, noise, reduced staffing).

Focal syndromes A number of lobar or focal neurologic syndromes may mimic delirium.

Temporal-parietal Patients with Wernicke's aphasia may appear delirious in that they do not
comprehend or obey and seem confused. However, the problem is restricted to language, while other
aspects of mental function are intact. Furthermore, fluent paraphasias are typically present with
Wernicke's and offer a major clue to the correct diagnosis.

Bitemporal dysfunction, if transient, may produce a transient global amnesia (TGA), in which the deficit is
restricted to memory. With more extensive bitemporal dysfunction, visual agnosia and cortical deafness
(either bitemporal or left temporal) or the Kluver-Bucy syndrome (apathy, visual agnosia, increased sexual
activity, and increased oral behavior) may be seen.
Occipital Anton's syndrome of cortical blindness and confabulation might be confused with delirium.
Careful examination, however, will reveal a lack of vision.
Frontal Patients with bifrontal lesions (eg, from tumor or trauma) often show akinetic mutism, lack of
spontaneity, lack of judgment, problems with recent or working memory, blunted or labile emotional
responses, and incontinence. These features may closely resemble delirium. Neuroimaging may be
required to differentiate frontal lesions from delirium and confusional states in difficult cases.
Confusion or delirium due to acute or subacute brain lesions, such as stroke or multifocal white matter
inflammation, may occur without focal deficits on examination [36-39]. One retrospective study of 127
consecutive neurology consultations for isolated acute mental status change found stroke as the cause in nine
patients (7 percent) [37]. Of these, three patients (2.7 percent) with stroke had no focal neurologic findings, and
one of these was a subarachnoid hemorrhage. Risk factors for delirium in the setting of stroke include pre-
existing cognitive impairment, infection, right hemispheric stroke, anterior circulation large vessel stroke, and
greater stroke severity [39].

Confusion or delirium may follow head injury even in the absence of focal neurologic deficits.

Nonconvulsive status epilepticus Nonconvulsive status epilepticus (NCSE) is under-recognized,

particularly in older patients. NCSE requires an EEG for detection and continuous EEG for management. Often
patients show no classic ictal features, but the following features should suggest the possibility of seizures:
prominent bilateral facial twitching, unexplained nystagmoid eye movements during obtunded periods,
spontaneous hippus, prolonged "post-ictal state," automatisms (lip smacking, chewing, or swallowing
movements), and acute aphasia or neglect without a structural lesion [40]. NCSE should also be considered in
the absence of these findings when the etiology of a confusional state remains obscure [41].

Dementia Dementia may sometimes be confused with delirium or confusion and vice-versa. However,
characteristic differences in progression and cognitive features usually distinguish these disorders.

In contrast to delirium, cognitive change in Alzheimer disease is typically insidious, progressive, without
much fluctuation, and occurs over a much longer time (months to years). Attention is relatively intact, as
are remote memories in the earlier stages. (See "Clinical features and diagnosis of Alzheimer disease",
section on 'Clinical features'.)
Dementia with Lewy bodies (DLB) is similar to Alzheimer disease but can be more easily confused with
delirium, because fluctuations and visual hallucinations are common and prominent. (See "Clinical
features and diagnosis of dementia with Lewy bodies".)

Primary psychiatric illnesses Delirium is commonly misdiagnosed as depression. Both are associated
with poor sleep and difficulty with attention or concentration. Agitated depression may be especially
problematic. However, depression is associated with dysphoria, and there is less fluctuation than in delirium.

Mania can be confused with hyperactive delirium with agitation, delusions, and psychotic behavior. However,
mania is usually associated with a history of previous episodes of mania or depression. In schizophrenia, the
delusions are usually highly systematized, the history is longer, and the sensorium is otherwise clear.