Delirium and Acute Personality Changes

There are multiple pathophysiologic mechanisms that may cause delirium; there is no final common pathway allowing a simple approach to diagnosis or treatment. The neurobiologic basis of delirium is, therefore, poorly understood, and diagnosis relies on a comprehensive clinical assessment with judicious use of ancillary studies. In general, areas of the brain that govern arousal, attention, insight, and judgment are affected. These include the subcortical ascending reticular activating system (ARAS) and integrated cortical regions. The ARAS predominantly serves arousal mechanisms, whereas integrated cortical function is necessary for proper orientation to person, place, and time, as well as higher cognitive functions.

Of the neurochemical pathogenic mechanisms of delirium, the best understood is the cholinergic system. Anticholinergic drugs are commonly associated with delirium in healthy patients but much more so in the elderly. Conditions that may predispose to delirium secondary to acetylcholine depletion include hypoxia, hypoglycemia, thiamine deficiency, and Alzheimer disease. In addition, many commonly used drugs may precipitate delirium due to secondary anticholinergic effects. Additional neurotransmitter systems that may precipitate delirium include GABA, endorphins, neuropeptides, serotonin, and norepinephrine. Other neurochemical precipitants of delirium include endogenous chemicals, such as proinflammatory cytokines and tumor necrosis factor-alpha, which may explain delirium occurring in the context of infection/sepsis, surgery, and hip fractures. The blood-brain barrier is weakened by sepsis, even in pediatric cases. Other than advanced age, pre-existing CNS disease, such as Alzheimer disease, Parkinson disease, stroke, etc., accounts for a significant increase in risk for delirium. Indeed, a new delirium in an elder patient may be a heralding sign of previously unrecognized or impending dementia.

The presentation of delirium is typically acute, over hours or days, and may persist for days to months. There may be a prodromal phase, especially in elder patients, including fatigue and lethargy, sleep disturbance, anxiety and/or depression, or restlessness. The acuity of onset differentiates delirium from dementia in most cases, although delirium in a demented patient may be difficult to detect, especially early in the course. Moreover, the severity of confusion may fluctuate throughout the day, becoming particularly more prominent toward night-time. Initially, there may be a subtle change in mental clarity, inattention, and disorientation before more obvious behavior changes take place. The patient is often very distractible, unable to maintain a cohesive train of thought or action. Patients are typically disoriented to time. In more advanced cases, patients may become more obviously drowsy and lethargic, even obtunded. However, the opposite may occur in some forms of delirium, where the patient becomes hypervigilant, irritable, and agitated, as seen in alcohol withdrawal. Hallucinations may occur. Cognitive deficits, including amnesia, aphasia, agnosia, and apraxia may also appear. Other clinical manifestations may include emotional lability, disturbance of sleep cycle, motor restlessness, and sometimes motor signs, such as asterixis, myoclonus, or action tremor. In the elder patient, the most common presentation is of a withdrawn, quiet state that may be easily mistaken for depression.

Delirium is often misattributed to psychiatric diagnoses—usually depression and catatonic schizophrenia in hypoactive deliriums, and personality disorders and psychosis in hyperactive deliriums. A patient with a first-episode psychosis or mania should be of typical age, that is, a young adult, and should appear generally well, not diaphoretic, flushed, befuddled, jaundiced, or clumsy. Psychiatric illness usually does NOT account for disorientation, and does NOT cause motor symptoms or fevers. Fluctuations in degree of alertness, variable motor signs, and uneven cognitive performance are expected in delirium and do not signify a manipulative personality. Use of antipsychotic medication may enable care, shorten duration of delirium, and improve mortality, even when the underlying cause is not psychiatric.

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