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
Highlights
Our study provides a unique insight into disturbed oxygen availability to the subarachnoid hemorrhage (SAH)-injured human cerebral cortex in association with cortical spreading depolarization (CSD) occurrence
It would appear that delayed ischemic neurological deterioration may result from major proximal arterial vasospasm, but in addition from CSD clusters that in particular contribute to delayed ischemia by causing subtle but noticeable stepwise alterations toward hypoxic tissue conditions
CSD clusters may play a crucial role in the development of delayed ischemia after SAH,[4,15,26] possibly in synergy with other mechanisms known to affect SAH-injured tissue, such as inflammation, blood–brain barrier disruption with edema formation and resulting mass effects, and endothelial dysfunction and thromboembolism.[1,27,28]
Summary
Delayed ischemic neurological deficit (DIND) contributes to poor outcome in subarachnoid hemorrhage (SAH) patients. Recurrent CSDs emerging spontaneously in metabolically compromised tissue, such as in the ischemic penumbra (in this situation termed peri-infarct depolarizations, [PIDs])[13] or after SAH,[4] irreversibly damage brain tissue at risk and thereby may lead to lesion growth.[10,14,15] Animal experiments have suggested that, under such conditions of impaired metabolic status, the vasodilatory response to CSD switches from a compensatory vasodilatory response to an inverse, vasoconstrictive neurovascular coupling, resulting in cortical spreading ischemia (CSI).[16,17,18,19] In a rat model, it has been hypothesized that, in principle, CSD activates both vasoconstriction and vasodilatation in a biphasic fashion, the ratio between the 2 being shifted toward vasoconstriction by ischemic/hypoxic tissue conditions.[20] Recently, combined recordings of regional cerebral blood flow (CBF) and ECoG using subdural optoelectrode strips have provided evidence that delayed ischemic stroke is associated with CSI in patients with SAH.[15] To our knowledge, this is the first detailed report of continuously corecorded tissue oxygen pressure (ptiO2) and CSD in human cerebral cortex. We hypothesized that CSDs, in particular if they occur in temporal clusters, reduce cortical oxygen availability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
