Tox Hot Topics: Excited Delirium—Who and What?

Eric Lee, MD with Jason B. Hack, MD

Excited delirium is a diagnosis obscured by limited understanding of its pathophysiology and legal implications of its brand. Formerly described as “Bell’s Mania”, named after Dr. Bell, an American physician practicing in Massachusetts in the mid 1800s, is a condition of delirium, agitation, aggression, and autonomic dysfunction. The syndrome of excited delirium has been described as a patient in florid delirium, who is typically sympathomimetic, aggressive, displays super-human strength, then has a period of quiescence, followed by cardiorespiratory failure and death. When it was first recognized in a cohort of psychiatric patients in the 1850’s, the mortality rate approached 75%. Little was known about causation for nearly 150 years until resurgence of clinical recognition in the late 1900s. Today, excited delirium is still a controversial diagnosis not accepted uniformly by all branches of medicine.

The American College of Emergency Physicians produced a statement a few years ago acknowledging excited delirium as a formal diagnosis. Currently, ICD-10 and the DSMV does not have Excited delirium as such. The condition has been refuted by the literature in the legal and medico-legal realm, as to not create a diagnosis that would distract and possibly defer investigation of wrongful death of patients with alleged EDS that expire in law enforcement custody.

In the last 10-15 years, the pathophysiology of the syndrome was explored. The majority of the work completed was on post-mortem brain specimens of victims of alleged EDS. Patients were found to have altered density and function of specific dopamine receptors. Serotonin receptors and signal function have also been described as abnormal. Specific proteins such as alpha-synuclein and heat proteins had altered levels in victims. The majority of these patients had a documented history of chronic substance abuse and a small subset had chronic psychiatric disease. The current hypothesis is long-term substance abuse combined with a genetic predisposition to altered neurophysiological pathways leads to altered neuroanatomy and function. Then there is an inciting event, typically cocaine, LSD, PCP, that sets of a cascade of abnormal function within the dopaminergic and serotonergic pathways leading the syndrome described as above.

The cause of death in these individuals is also shrouded by controversy. Media attention to victims who were displaying an EDS picture who died in police custody created a storm of attention on use of force by judicial system employees. Positional asphyxia and Taser use became a focus as potential cause of death. This both have been refuted by studies done in healthy cohorts. Potential alternate explanations are fatal arrhythmia or cardiovascular collapse from central autonomic dysregulation. None of the above has been proven to date and is unlikely to be in the future.

Excited delirium is likely a genuine pathophysiological state caused by alterations of neuroanatomical pathways and function in a specific cohort of patients with underlying genetic predisposition. However, it is likely to remain a diagnosis that raises doubt due to its legal implications.


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