From a clinical perspective, the metabolic data can support a deleterious effect, but the effect on clinical outcome is critical in determining if the events are relevant as a potential target for therapy. The occurrence and severity of CSD has been closely linked to both development of new stroke as well as clinical outcome in both retrospective and prospective series. In subarachnoid hemorrhage, Dreier(13) reported a direct association with clinical delayed ischemic neurologic defect (DIND) and the presence of a cluster of SD. Furthermore, in this small series, the patients who went on to develop stroke had markedly longer periods of depression, indicating inability of the tissue to recover from the event compared to patients without delayed stroke. The most extensive clinical outcome data is from traumatic brain injury (TBI)(14,15) where the presence of any CSD showed a non-significant trend toward predicting worse outcome, however CSD occurring in already dysfunctional tissue (termed isoelectric spreading depolarization or ISD) was stronger predictor of clinical outcome than a composite score of most standard variables through to predict outcome (OR 7.58 (95%CI 2.64-21.8) for ISD compared to 1.76(95%CI 1.26-2.46) for the composite prognostic score)(15).