CNS Arousal Systems: Possible Role in Delirium

Delirium is often considered a global and nonspecific alteration in cerebral function. However, the recent clinical evidence for heterogeneity within the syndrome of delirium suggests that different systems of the brain may be important in different kinds of delirium. Some forms of delirium, such as anticholinergic toxicity and hepatic encephalopathy, may be caused by drugs or toxins acting on specific brain neurochemical systems. The neurophysiological bases of the control of normal arousal and attention are still relatively poorly understood. However, the recent appreciation of the existence of neurotransmitter-specific projections from the hypothalamus and brain stem directly to the cerebral cortex has spurred new research. Some of these projections may be important in particular kinds of delirium; for instance, evidence from a number of different lines of research implicates GABA systems in the brain as being important in the delirium of hepatic encephalopathy. Cholinergic neurons in the basal forebrain and pons innervate the cerebral cortex. Both of these neurons, but particularly the pontine group, may be important in the delirium of anticholinergic toxicity. Thus, more research on the physiology of these systems in normal sleep and arousal, as well as in pathophysiological states, is indicated. Little is known about changes in these systems with aging. The well-known degeneration in cholinergic systems in Alzheimer's disease, and the sensitivity of individuals with Alzheimer's disease to anticholinergic toxicity, suggest a role of central cholinergic systems in anticholinergic delirium in demented patients. Further research into the involvement of the other systems in aging and delirium apparently would be fruitful.