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BACKGROUND AND PURPOSE Collaterals may compensate for reduced blood flow in acute ischemic stroke, yet endurance and quality of collateral perfusion may vary. Collateral sustenance of penumbra may falter after initial recruitment, resulting in progressive ischemia and clinical deficits. Delayed collateral failure may extend the time window for revascularization, even after failed intravenous thrombolysis. CASE DESCRIPTION A 76-year-old woman returned to normal from National Institutes of Health Stroke Scale (NIHSS) score of 18 following intravenous thrombolysis, despite persistent occlusion of the left middle cerebral artery. Subsequent deterioration was successfully reversed with mechanical thrombectomy almost 14 hours after symptom onset. CONCLUSIONS Early clinical improvement or deterioration may reflect collateral perfusion, not necessarily recanalization or reocclusion. The definition of collateral failure must incorporate the expected role and endurance of collaterals. Further investigation of collateral pathophysiology may reveal predictive clinical or imaging features and disclose collateral therapeutic approaches to augment revascularization. J Neuroimaging 2010;20:78-82. [ABSTRACT FROM AUTHOR]