Spreading Depolarizations and Late Secondary Insults after Traumatic Brain Injury

Abstract

Here we investigated the incidence of cortical spreading depolarizations (spreading depression and peri-infarct depolarization) after traumatic brain injury (TBI) and their relationship to systemic physiologic values during neurointensive care. Subdural electrode strips were placed on peri-contusional cortex in 32 patients who underwent surgical treatment for TBI. Prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly nursing chart data. Recordings were 84 hr (median) per patient and 2,503 hr in total. In 17 patients (53%), 280 spreading depolarizations (spreading depressions and peri-infarct depolarizations) were observed. Depolarizations occurred in a bimodal pattern with peak incidence on days 1 and 7. The probability of a depolarization occurring increased significantly as a function of declining mean arterial pressure (MAP; R(2) = 0.78; p < 0.001) and cerebral perfusion pressure (R(2) = 0.85; p < 0.01), and increasing core temperature (R(2) = 0.44; p < 0.05). Depolarization probability was 7% for MAP values of >100 mm Hg but 33% for MAP of < or =70 mm Hg. Temperatures of < or =38.4 degrees C were associated with a 21% depolarization risk, compared to 63% for >38.4 degrees C. Intracranial pressures were higher in patients with depolarizations (18.3 +/- 9.3 vs. 13.5 +/- 6.7 mm Hg; p < 0.001). We conclude that depolarization phenomena are a common cortical pathology in TBI. Their association with lower perfusion levels and higher temperatures suggests that the labile balance of energy supply and demand is an important determinant of their occurrence. Monitoring of depolarizations might serve as a functional measure to guide therapeutic efforts and their blockade may provide an additional line of defense against the effects of secondary insults.

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

“…The spontaneous occurrence of depolarizations in some 50% to 60% of such cases has now been shown by independent investigators using different monitoring techniques (Mayevsky et al, 1996;Strong et al, 2002) and also at seven different centers within the COSBID consortium Hartings et al, 2009). Patterns of CSD vary widely, from sparse single events in some patients to temporal clusters of events repeating every 20 to 30 minutes for X12 hours in others, and sometimes recurring after 5 to 7 days ( Figure 6).…”

Real-Time Monitoring of Changes in Brain Extracellular Sodium and Potassium Concentrations and Intracranial Pressure after Selective Vasopressin-1a Receptor Inhibition following Focal Traumatic Brain Injury in Rats

“…CSD usually signifies a labile balance of energy supply and demand, which contributes to its occurrence. [51][52][53] Multiple mechanisms may participate in the recovery process including ion channels, pumps and exchangers, spatial buffering by astrocytes and their end-foot processes, and bulk flow through the ECF, which drains into the cerebrospinal fluid (CSF). 47,48,50 It is important to emphasize that post-CCI [Na + ] e and [K + ] e alterations were transient in untreated animals and that elevation of ICP occurred over the same time period, whereas the enhanced rate of recovery of [Na + ] e after SR49059 treatment prevented the development of elevated ICP.…”

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

“…In rodent models of experimental ischemia, CSD resulted in reduced cerebral blood flow [76] and increased infarct volume [77]. In human studies, cortical spreading depression has been associated with metabolic stress and injury, as measured by elevation in glutamate and lactate/pyruvate ratio, as well as low brain tissue oxygenation [78]. Its effects are not clearly mediated through or detected by rises in intracranial pressure [79], and thus CSD may result in secondary injury independent of intracranial pressure.…”