Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A.
Effective development of targeted therapies to prevent and treat delirium requires an understanding of the underlying physiologic processes. Historically, delirium has been considered a reflection of diffuse cerebral metabolic insufficiency, which may be a result of some combination of abnormal blood flow, abnormal energy metabolism, abnormal neurotransmission, and abnormal cellular maintenance processes. Perspectives on the pathophysiology underlying hepatic encephalopathy, sepsis-associated encephalopathy, critical illness delirium, and alcohol withdrawal delirium are discussed. Given the diverse etiologic mechanisms, it is likely that the pathophysiology underlying delirium is also quite diverse. Additional investigation is required to identify therapeutic targets for prevention and treatment.