Altered mental status natural history, complications and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]


Natural History, Complications and Prognosis

Delirium, stupor, and coma represent a broad spectrum of acute brain dysfunction and are associated with an impairment of consciousness. There are two interrelated domains of neurologic function that are related to consciousness:

  1. Content
  2. Level (also known as arousal) of consciousness.

The content of consciousness has many components such as orientation, perception, executive function, and memory, and is mediated at the cortical level. The level (or arousal) of consciousness signifies the patient’s wakeful state and reactivity to surrounding stimuli. This is mediated at the ascending reticular activating system located in the brainstem. Traditionally, terms such as lethargic, drowsy, or somnolent have been used to describe level or arousal of consciousness. Because these descriptors can have different meanings for different clinicians, using a structured arousal scale such as the Richmond Agitation Sedation Scale (RASS) may be a more reliable method to describe altered level of consciousness. This scale ranges from -5 (unresponsive to pain and voice) to +4 (extreme combativeness). As the patient’s level of consciousness becomes more disturbed, the concern for an underlying life threatening acute medical illness should similarly increase. Patients with acute brain dysfunction can not only fluctuate between different RASS scores, but can also transition between delirium, stupor, and coma.

Stupor and Coma: Definitions and their Epidemiology in the Emergency Department

Stupor and coma occurs in 5 to 9% of older ED patients and when present, are considered to be medical emergencies that require immediate evaluation. These two forms of acute brain dysfunction occur over a period of hours to days and represent the most severe disruptions in both the level and content of consciousness. Stupor (RASS −4) is a condition of deep sleep or similar behavioral unresponsiveness from which the patient can be aroused only with vigorous and continuous stimulation. Coma (RASS −5) is defined as a state of unresponsiveness in which the patient cannot be aroused with any stimuli.

Delirium: Definitions and its Epidemiology in the Emergency Department

Delirium is an acute disturbance of consciousness (i.e. attention) that is accompanied by an acute loss in cognition that is not better explained by a preexisting dementia. This form of acute brain dysfunction occurs in 8 to 10% of patients of older ED patients. Similar to stupor and coma, delirium occurs over a period of hours and days, and its course tends to wax and wane throughout the day. In contrast to stupor and coma, however, some elements of the level and content of consciousness are maintained in patients with delirium. The degree of impairment in the level of consciousness can be variable, ranging from moderate sleepiness (RASS −3) to extreme combativeness (RASS +4). Patients with delirium also have inattention which is considered a cardinal feature of delirium. The impairment of content of consciousness is similarly variable and leads to an acute loss in cognition. Examples of such impairments observed in delirious patients are disorganized thought, perceptual disturbances, and disorientation.

The Psychomotor Subtypes of Delirium

Delirium can be further classified into three psychomotor subtypes: hypoactive, hyperactive, and mixed. Hypoactive (RASS < 0) delirium is described as “quiet” delirium and is characterized by psychomotor retardation; delirious patients with this subtype can appear drowsy, somnolent, or even lethargic. Because the clinical presentation can be very subtle, hypoactive delirium is frequently undetected by health care providers,21 and is often attributed to other etiologies such as depression or fatigue. To the contrary, patients with hyperactive delirium (RASS > 0) have increased psychomotor activity and may appear restless, anxious, agitated, or combative. Hyperactive delirium is more easily recognized by health care providers. Mixed-type delirium exhibits fluctuating levels of psychomotor activity; the patient can exhibit hypoactive symptomatology at one moment and hyperactive symptomatology several hours or even seconds later. Hypoactive delirium and mixed-type delirium appear to be the predominant subtypes in older patients regardless of the clinical setting. In the ED specifically, hyperactive delirium is the least common subtype.

It is hypothesized that each psychomotor subtype has different underlying pathophysiological mechanisms. Though the mechanisms are unclear, it is hypothesized that each delirium subtypes has differential neurotransmitter activity (cholinergic, dopamine, serotonin, and gamma-aminobutyric acid). Each psychomotor subtype may also be cause by different etiologies. Delirium caused by an infection or metabolic derangement is more likely to be the hypoactive subtype, whereas delirium caused by alcohol or benzodiazepine withdrawal is more likely to be the hyperactive subtype. The psychomotor subtypes of delirium may also have a differential effect on clinical course and outcomes. In 225 older patients admitted to a post acute care facility, Kiely at al. observed that patients with hypoactive delirium had the highest 1-year mortality rate compared with the other subtypes.

Delirium versus Dementia

Delirium is distinct from dementia, yet many clinicians use these terms interchangeably. It is important to note, however, that dementia is an important predisposing factor to delirium, and patients can have both conditions concurrently. As previously mentioned, the loss of cognition observed in delirium tends to occur rapidly, and its course tends to fluctuate throughout the day. The loss of cognition observed in dementia is usually gradual (over months to years), and its course tends to be stable. Patients with delirium also have inattention, which is considered the cardinal feature of delirium where as attention is usually preserved in patients with dementia. Altered level of consciousness, disorganized thinking, sleep-wake cycle disturbances, and perceptual disturbances are also commonly observed in delirium, whereas these characteristics are typically absent in dementia.

There are instances when the clinical features of delirium and dementia overlap, making them difficult to distinguish from each other. This is especially the case in patients with end-stage dementia, where they can exhibit symptoms of inattention, altered level of consciousness, disorganized thinking, sleep-wake cycle disturbances, and perceptual disturbances in the absence of delirium.34 When patients with end-stage dementia develop delirium, an acute change in mental status is still observed, and any pre-existing abnormalities in cognition and level of consciousness will likely worsen. For this reason, diagnosing delirium can be extremely challenging in patients with severe dementia and establishing their baseline mental status is critical to the diagnosis.

Delirium is classically thought of as reversible and is usually precipitated by an underlying medical illness. However, there are also a proportion of patients whose delirium is not transient, and their symptoms can persist for months or even years. Dementia is thought of as irreversible and not secondary to an underlying medical illness. However, there are circumstances in which dementia may be reversible. Hypothyroidism, normal pressure hydrocephalus, vitamin B12 deficiency, and depression are examples of illnesses that can cause reversible dementia or a dementia-like illness (pseudodementia). One meta-analysis comprised of 39 articles reported that 9% of dementia were potentially reversible, but only 0.6% of the dementia cases showed any improvement in cognition after the reversible cause was addressed.

Dementia with Lewy bodies is the second most common type of dementia (after Alzheimer’s) and deserves special mention because it can be very challenging to distinguish from delirium. Similar to delirium, the loss of cognition observed in dementia with Lewy bodies can be rapid, and it can fluctuate over several hours or days. Perceptual disturbances are also commonly observed in dementia with Lewy bodies. Patients with dementia with Lewy bodies, however, have Parkinsonian motor symptoms such as cog wheeling, shuffling gait, stiff movements, and reduced arm-swing during walking; these motor symptoms are usually absent in patients with delirium. Differentiating between dementia with Lewy bodies and delirium can be difficult in the ED and may require a detailed evaluation by a neurologist or psychiatrist.