2 research outputs found
Terminal spreading depolarization and electrical silence in death of human cerebral cortex
Objective: Restoring the circulation is the primary goal in emergency
treatment of cerebral ischemia. However, better understanding of how the brain
responds to energy depletion could help predict the time available for
resuscitation until irreversible damage and advance development of
interventions that prolong this span. Experimentally, injury to central
neurons begins only with anoxic depolarization. This potentially reversible,
spreading wave typically starts 2 to 5 minutes after the onset of severe
ischemia, marking the onset of a toxic intraneuronal change that eventually
results in irreversible injury. Methods: To investigate this in the human
brain, we performed recordings with either subdural electrode strips (n = 4)
or intraparenchymal electrode arrays (n = 5) in patients with devastating
brain injury that resulted in activation of a Do Not Resuscitate–Comfort Care
order followed by terminal extubation. Results: Withdrawal of life‐sustaining
therapies produced a decline in brain tissue partial pressure of oxygen
(ptiO2) and circulatory arrest. Silencing of spontaneous electrical activity
developed simultaneously across regional electrode arrays in 8 patients. This
silencing, termed “nonspreading depression,” developed during the steep
falling phase of ptiO2 (intraparenchymal sensor, n = 6) at 11 (interquartile
range [IQR] = 7–14) mmHg. Terminal spreading depolarizations started to
propagate between electrodes 3.9 (IQR = 2.6–6.3) minutes after onset of the
final drop in perfusion and 13 to 266 seconds after nonspreading depression.
In 1 patient, terminal spreading depolarization induced the initial
electrocerebral silence in a spreading depression pattern; circulatory arrest
developed thereafter. Interpretation: These results provide fundamental
insight into the neurobiology of dying and have important implications for
survivable cerebral ischemic insults. Ann Neurol 2018;83:295–31