Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex

Abstract

ObjectiveDelayed ischemic neurological deficit (DIND) contributes to poor outcome in subarachnoid hemorrhage (SAH) patients. Because there is continuing uncertainty as to whether proximal cerebral artery vasospasm is the only cause of DIND, other processes should be considered. A potential candidate is cortical spreading depolarization (CSD)-induced hypoxia. We hypothesized that recurrent CSDs influence cortical oxygen availability.MethodsCenters in the Cooperative Study of Brain Injury Depolarizations (COSBID) recruited 9 patients with severe SAH, who underwent open neurosurgery. We used simultaneous, colocalized recordings of electrocorticography and tissue oxygen pressure (ptiO2) in human cerebral cortex. We screened for delayed cortical infarcts by using sequential brain imaging and investigated cerebral vasospasm by angiography or time-of-flight magnetic resonance imaging.ResultsIn a total recording time of 850 hours, 120 CSDs were found in 8 of 9 patients. Fifty-five CSDs (∼46%) were found in only 2 of 9 patients, who later developed DIND. Eighty-nine (∼75%) of all CSDs occurred between the 5th and 7th day after SAH, and 96 (80%) arose within temporal clusters of recurrent CSD. Clusters of CSD occurred simultaneously, with mainly biphasic CSD-associated ptiO2 responses comprising a primary hypoxic and a secondary hyperoxic phase. The frequency of CSD correlated positively with the duration of the hypoxic phase and negatively with that of the hyperoxic phase. Hypoxic phases significantly increased stepwise within CSD clusters; particularly in DIND patients, biphasic ptiO2 responses changed to monophasic ptiO2 decreases within these clusters. Monophasic hypoxic ptiO2 responses to CSD were found predominantly in DIND patients.InterpretationWe attribute these clinical ptiO2 findings mainly to changes in local blood flow in the cortical microcirculation but also to augmented metabolism. Besides classical contributors like proximal cerebral vasospasm, CSD clusters may reduce O2 supply and increase O2 consumption, and thereby promote DIND. ANN NEUROL 2010;67:607–617

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

“…2010). Similar deterioration has recently been observed in SAH patients: measurement of tissue oxygen partial pressure revealed progressive stepwise decline with subsequent CSDs within clusters (Bosche et al, 2010).…”

“…Such clusters were associated with spreading ischemias that were significantly longer (duration of up to 144 minutes) than those coupled to isolated spreading depolarizations. Consistently, Bosche et al (2010) reported that progressively hypoxic responses of P ti O 2 can develop during clusters of spreading depolarizations.…”

Distinct Spatiotemporal Patterns of Spreading Depolarizations during Early Infarct Evolution: Evidence from Real-Time Imaging

“…Even though the effect of secondary CBF LSF waves on a further reduction of CBF in inner zones of the penumbra seems rather small from our results (see Figure 6), it should be emphasized that multiple CSDs/PIDs are to be expected in the course of focal ischemia and stroke resulting in additive deleterious effects, in particular, if clusters of CSD/PID appear (Bosche et al, 2010;Dohmen et al, 2008;Dreier et al, 2006). In SAH patients, for example, we have recently shown that within clusters of CSD, oxygen availability decreases considerably (Bosche et al, 2010;Dohmen et al, 2008;Dreier et al, 2006). Similarly, extracellular glucose availability may decrease after CSD passage, which even occurs under almost physiological conditions (Hashemi et al, 2009).…”

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

“…Invasive measures of brain tissue oxygenation showed that waves of CSD following SAH resulted in significant stress on the balance of brain oxygen supply and demand, causing waves of brain tissue hypoxia followed by rebound hyperoxia. This biphasic pattern transitioned to monophasic hypoxia once a delayed neurological ischemic deficit has occurred, suggesting that CSD can cause irreversible injury when occurring in vulnerable tissue [81].…”