DELIRIUM: Advances in Diagnosis, Pathophysiology, and Treatment
Section snippets
RISK FACTORS
Several studies have sought to identify risk factors associated with delirium. At any age, polypharmacy, substance intoxication, and multiple medical problems are common risk factors for delirium.37, 136
Thiamine deficiency often goes unnoticed in nonalcoholic patients and is an underappreciated cause or risk factor for delirium.85 Low serum albumin is an important risk factor at any age because of its role in transporting many drugs through the bloodstream. More unbound drug becomes available
DIAGNOSIS AND ASSESSMENT
Diagnostic criteria for delirium were first published in the Diagnostic and Statistical Manual III (DSM-III). Differentiation of delirium from other so-called organic mental disorders was not possible before DSM-III. DSM, published in 1952,17 described acute and chronic brain syndromes, which were considered disorders caused by or associated with impairment of brain-tissue function. They were “characterized by a basic syndrome consisting of (1) impairment of orientation, (2) impairment of
PHENOMENOLOGY
The phenomenology of delirium has been characterized inadequately. The more knowledge we have about the incidence and interrelationships of various delirium symptoms, the greater the accuracy we can expect from future DSM versions and the more information we can elucidate about underlying neuropathogenesis and syndrome subtypes. Different symptom profiles might predict outcomes. For example, Wada and Yamaguchi143 reported more cognitive impairment, sleep-wake cycle disturbance, and mood
DELIRIUM ASSESSMENT METHODS
Several assessment instruments for delirium have been developed during the past decade and were recently reviewed.132 Some were developed without regard to any gold standard (i.e., DSM criteria). The validation of some methods was confounded by comorbid dementia in the populations evaluated. Some screening instruments are not specific enough or sufficiently detailed to assess the breadth of delirium symptoms, and false-positive cases may be identified. Nonetheless, the existence of efforts to
NEUROPATHOPHYSIOLOGY
Lesion studies and functional brain imaging may offer clues about which brain regions are affected during delirium. Prefrontal cortex; right cerebral hemisphere (especially parietal); and subcortical nuclei (especially right-sided thalamus and caudate) are important areas.131 For example, strokes in the anteromedial thalamus10, 31, 110 and posterior parietal cortex11, 50, 75, 94 present with severe delirium as the main clinical manifestation. In depressed patients, caudate lesions27, 66 and
NEUROTRANSMISSION IN DELIRIUM
Alterations in neurotransmission underlying delirium include cholinergic, dopaminergic, serotonergic, and GABA-ergic systems, with noradrenergic, glutamatergic, opiatergic, and histaminergic systems possibly also involved. Many of these neurotransmitters play an important role in the neurologic pathways delineated as possibly underlying delirium (see previous section). The cholinergic and dopaminergic systems have received the most attention, with decreased acetylcholine and increased dopamine
TREATMENT
Standard management and treatment of delirium begins with a careful search for underlying causes that might be reversed. Environmental manipulations, such as the use of calendars, night lights, family photos, and reorientation by staff, are also implemented. Treatment of the delirium itself needs to occur simultaneously with these measures and is largely pharmacologic, most often using haloperidol. Interestingly, haloperidol lowers glucose use during PET scans of humans in frontal and anterior
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Address reprint requests to Paula T. Trzepacz, MD, WPIC, 3811 O'Hara Street, Pittsburgh, PA 15213
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From the Neuropsychiatry Program, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania