Brain death is a clinical diagnosis, based on established guidelines, which in the United States is a legally and ethically acceptable criterion for death. The neuropathology of brain death remains incompletely understood. In the past, extensive neuronal injury has been reported in autopsies of brain death patients (“respirator brain”). However, most of these patients in the past were supported in the ICU for long periods of time, prior to the current practice of discontinuing support or moving toward rapid organ harvest once brain death is declared. A recent report (Wijdicks et al, 2008) sought to describe the modern-day neuropathology of brain death.
The authors reviewed the neuropathology of 43 brain dead patients (25% of the total number of brain death cases) at a single institution over a 6-year period. Patients all met rigorous criteria for brain death according to current practice guidelines of the American Academy of Neurology (AAN). Brains were fixed using 10% formalin, and a standard neuropathologic sampling of tissue throughout the brain was undertaken.
The patients ranged in age from 19 to 80 (median 27 years). A total of 73% were male, and trauma was the most common cause of brain injury (80%) followed by stroke and cardiac arrest. Time from initial injury to brain death varied with 27/41 (66%) patients being declared brain dead less than 24 h and 9/41 (22%) greater than 48 h after the inciting event. Time to fixation of the brain after brain death declaration was less than 12 h in 12 patients (29%) and between 12 and 36 h in the other 29 patients.
Other than the changes associated with the mechanism of injury (e.g., contusions and axonal injury in trauma patients), the authors found varying degrees of neuronal ischemic changes throughout the brain. Moderate to severe neuronal ischemic changes were found in the thalamus in 34% of patients, the frontal lobe in 64%, the parietal lobe in 61%, the occipital lobe in 68%, the cerebellum in 52%, the midbrain in 37%, the pons in 41%, and the medulla in 40%. In most patients, some areas of the brain were spared moderate to severe neuronal injury. The two patients with anoxic injury demonstrated severe neuronal necrosis throughout the hemispheres with relatively less injury in the brainstem.
This report represents a large, modern, careful neuropathologic examination of brain death specimens. The most striking finding of this study is the variability in neuropathology of patients who all met identical criteria for brain death. The historical changes of massive neuronal necrosis (“respirator brain”) described previously in brain death specimens were not observed. This finding emphasizes that a variety of cerebral insults and pathologies can lead to a patient clinically fulfilling the criteria for brain death. This heterogeneity once again reinforces that a diagnosis of brain death should be made on clinical grounds rather than with radiographic or pathologic criteria. Since in the United States such importance is ascribed to the determination of brain death (due to organ harvesting laws), we must continue to be vigilant that strict criteria for brain death are being uniformly applied.
