Neural mechanisms of delirium: Current hypotheses and evolving concepts

The purpose of this article is to review current knowledge regarding potent ial neural mechanisms of delirium. A MEDLINE search for relevant English la nguage articles was undertaken using various combinations of delirium (incl uding cognitive disorders, encephalopathy, and confusion) with pathogenesis and pathophysiology. These articles were scanned for content related to hy potheses concerning the neurobiology of delirium Additional references were obtained from a manual search of the bibliography of these articles. A sec ondary MEDLINE search of delirium with the mechanism in question (i.e., ser otonin, acetylcholine, etc.) was then undertaken. Literature review was las t updated as of April 1998. Despite being a common problem among elderly pa tients, the mechanisms of delirium are poorly understood Delirium is a synd rome that may occur as the result of multiple complex interacting neurotran smitter systems and pathologic processes. The neurotransmitters acetylcholi ne and serotonin may play particularly important roles in common medical an d surgical delirium. Other neurotransmitters such as dopamine and gamma-ami nobutyric acid each may be involved in the development of delirium under sp ecial conditions. Other neurobiologic factors such as cytokines, cortisol a bnormalities, and oxygen free radicals win require further study to define their role in delirium. Distinct meuropathologic processes leading to delir ium are beginning to be defined Such mechanisms may differ in various clini cal settings. There is probably no final common pathway to delirium but rat her delirium is the final common symptom of multiple neurotransmitter abnor malities. Further situation-specific studies of delirium pathophysiology sh ould lead to more effective prevention and treatment strategies.