Applied Neuroscience in the Study of Delirium: The Classic Work of Engel and Romano

“The thesis is presented that a derangement in the general functional metabolism of the brain underlies all instances of delirium and that this is reflected at the clinical level by a characteristic disturbance in cognitive functions and at the physiologic level by a characteristic generalized slowing of the electroencephalogram.”¹

Exquisite descriptive studies of delirium date back 2,500 years to the works of Hippocrates (460-366 B.C.) (Lipowski 1990). The next article in Classic Series honors the seminal work of George L. Engel and John Romano from the University of Rochester. The much-quoted review article reprinted here summarizes a series of their research conducted in the 1940-1950s on the electroencephalographic study of delirium. Zbigniew Lipowski, who wrote several definitive texts on the subject of delirium, reflected on the impact of Engel and Romano's work: “The investigators went beyond the traditional descriptive and speculative approach and embarked on a scientific inquiry into the pathophysiological mechanisms underlying delirium. They … formulated, more clearly than anyone before them, a unified concept of the syndrome, one that transcended the superficial variabililty of its behavioral features.”²

Engel and Romano begin their article with a criticism that unfortunately remains true today, namely that most physicians have insufficient training, understanding, or ability to recognize delirium. They provide a detailed review of what was known about brain metabolism, which in the 1950s was an area of research just starting to rapidly develop. They subsequently review a series of their own studies examining the role of the electroencephalogram (EEG) in the detection of delirium. They found that the administration of certain drugs and shifts in glucose levels, oxygen saturation, or acid-base balance resulted in reversible slowing of the EEG. These studies led to their core hypothesis that delirium represents a syndrome of cerebral insufficiency that is measurable by the slowing of the background EEG. They also reported that EEG slowing in subclinical delirium could still produce background rhythm that fell within a normal range. Demonstrating ebullience toward the use of the EEG, Engel and Romano maintained that “the electroencephalogram reflects cerebral insufficiency as reliably, if not more reliably, than the electrocardiogram reflects myocardial insufficiency.”¹ Nevertheless, they recognized several practical limitations of the EEG in the clinical assessment of delirium. For example, they suggested that a repeat EEG in clinically remitted patients is often needed to prove that the background rhythm was slowed during acute delirium.

Engel and Romano's article was the primary reference for the description of delirium until the DSM-III was published in 1980 and is an example of superior descriptive writing, enriched by empiric data and entertaining polemic that covers many issues that remain germane today.