FORT MYERS, FLA—Delirium is associated with a remarkably wide variety of neuropsychiatric disorders, including alcohol intoxication and/or withdrawal, stroke, head injury, and adverse drug reactions. But despite decades of studies and case reports, the syndrome still awaits a definitive definition. Even the DSM-IV criteria resort to such vague terms as “disturbance of consciousness”—a phrase that only hints at delirium’s essence and, from a clinical standpoint, is perhaps only slightly more useful than “I can’t define it, but I know it when I see it.”

As part of their efforts to better understand delirium phenomenology, Paula T. Trzepacz, MD, and colleagues recently examined the frequency with which various symptoms occur in patients with delirium. The goal of the study, which the researchers reported at the annual meeting of the American Neuropsychiatric Association, was to try to identify which manifestations represent the essential features of delirium.

“I think it is quite possible that there are core symptoms that appear consistently across deliria of different etiologies,” said Dr. Trzepacz, who is Medical Director of the US Neurosciences Division at Eli Lilly and Company and also holds academic appointments at the University of Mississippi School of Medicine in Jackson and Tufts University School of Medicine in Boston. Unfortunately, the existing literature—which Dr. Trzepacz termed “a mess”—has barely examined the issue of core symptoms; studies typically assessed only a few of delirium’s many features and rarely used standardized instruments in patient evaluations. As a result, the prevalence of symptoms has often varied dramatically between studies. For example, attention problems were apparent in 100% of patients in one study but in only 17% in another.

To remedy this dearth of reliable data, Dr. Trzepacz and colleagues at the University of Mississippi analyzed findings from 24 patients, ages 18 to 89, who had delirium due to an assortment of DSM-IV diagnoses. Delirium symptoms were assessed using the Delirium Rating Scale-Revised-98 (DRS-R-98)—an instrument that allows clinicians to rate a broad range of symptoms associated with delirium—as well as with the Cognitive Test for Delirium (CTD). The evaluations were conducted as part of a larger study examining the validity of the DRS-R-98 and as such included patients both with and without delirium; thus the raters were blind to a given patient’s delirium status.

A DISORDER OF ATTENTION?

The researchers made no a priori assumptions regarding the essential features of delirium. Still, Dr. Trzepacz says, she was not surprised by the list of symptoms that turned out to be nearly universal in this study population and that may qualify as core symptoms. Leading the pack were attention difficulties, which were present in 100% of the patients and appear to be a critical component of delirium. Not only were attention problems moderate to severe in 88% of the subjects, but analyses revealed that the CTD attention span measure correlated with more DRS-R-98 items (five) than did any other CTD item. In a chapter on delirium that Dr. Trzepacz cowrote several years ago, she noted that “delirium has been viewed by some, especially neurologists, primarily as a disturbance of attention”; the findings from the current study are largely consistent with that view.

However, several other symptoms were present in the vast majority of patients as well, including disorientation (96%), impairment in long-term (96%) or short-term (92%) memory, visuospatial deficits (96%), and abnormalities in the sleep-wake cycle (92%). These symptoms are also likely to be core features of delirium; so, perhaps, are three additional symptoms that were relatively common, though absent in at least a fifth of the patients: abnormal thought processes (79%), motor agitation (79%), and language abnormalities (67%).

DOES ETIOLOGY MATTER?

Several other symptoms—perceptual disturbances (63%), affective lability (54%), and delusions (42%)—were present in less than two thirds of patients but do seem to have some relationship with delirium. The presence of these “associated symptoms,” Dr. Trzepacz believes, may depend on the specific etiology behind the delirium or on individual differences in neuroanatomy. “I don’t know whether it’s either or both because we don’t have good studies,” Dr. Trzepacz said. “We need to do prospective studies on fairly pure etiologic groups of delirious patients to see whether they consistently have these associated symptoms.”

Although the associated symptoms are not universally present, they do have clinical utility. For example, the presence of visual hallucinations or certain types of delusions can help rule out competing diagnoses in patients with delirium.

MISGUIDED TREATMENT

Identification of delirium’s core symptoms has several treatment implications, Dr. Trzepacz noted. For example, clinicians are sometimes more inclined to treat delirium if patients have psychotic symptoms. That approach makes little sense, Dr. Trzepacz said, “because those aren’t the core symptoms you want to treat; they’re not really the defining symptoms of the disorder.” Moreover, if treatment is contingent on the presence of psychotic symptoms or other associated features, rather than on core symptoms, “you’ll be missing a lot of patients. So an understanding of what are core symptoms and what aren’t, and then basing treatment on the presence of a number of core symptoms, is very important.”

This line of research may also aid efforts to identify the putative final common neural pathway that funnels the diverse array of delirium etiologies into a single coherent syndrome. Though the neuroanatomic basis of delirium is not as well understood as that of, say, depression, evidence points to structural or functional abnormalities in the right hemisphere—particularly in prefrontal cortex and anterior thalamus—as well as in the lingual gyrus and fusiform cortex. From a neurotransmitter standpoint, the dopaminergic and cholinergic systems appear to be particularly important. “These core symptoms should be a way for us to better pull all of this together,” Dr. Trzepacz said. Ultimately, the findings may “open the door to more specific treatments that will allow us to ‘fix’ the neuroanatomic pathways” that cause delirium.

—Peter Doskoch

Suggested Reading
1. Trzepacz PT, Mittal D, Torres R, et al. Validation of the Delirium Rating Scale-Revised-98: Comparison to the Delirium Rating Scale and Cognitive Test for Delirium. J Neuropsychiatry Clin Neurosci. In press.
2. Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Semin Clin Neuropsychiatry. 2000;5:132-148.

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