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To the Editor:The controversy about the significance of early ischemic changes (EIC) on CT after acute stroke by von Kummer, Lyden, and Davis and Donnan1–3 nicely summarizes the issues except for what, in my mind, is the most likely explanation for the discrepancy between the NINDS and ECASS conclusions on this subject. I would also like to propose an alternative way of looking at the “more or less than one third MCA territory” controversy.The aim of treatment with intravenous tPA is to reperfuse tissue that is hypoperfused but still viable (penumbra). While there are undoubtedly other variables that are important, the overwhelming burden of animal and human data have shown that time is critical for the existence of penumbra; penumbral tissue is more plentiful the earlier the patient is treated after the stroke onset. Therefore, when NINDS patients were treated on average 90 minutes after stroke onset, the core of already infarcted tissue, represented by areas of EIC on CT, was in most cases likely still surrounded by substantial salvageable, normally appearing penumbral brain tissue on CT. Such patients could, and did, benefit from reperfusion after intravenous tPA. However, 240 to 300 minutes after the stroke, when the average ECASS patient was treated, the core would be larger (hence more patients with EIC in >⅓ MCA), and the regions of EIC would most likely be surrounded by relatively less penumbra. The result of treating such patients, therefore, is risk with less likelihood of much benefit. This logically would explain why EIC by themselves, whatever their extent, did not predict lack of benefit from tPA treatment in the NINDS patients, but why extensive EIC were associated with risk and no benefit in ECASS.This hypothesis is supported by clinical observation of patients seen within 3 hours of stroke …

NIHSS/EIC Mismatch Explains the > 1/3 MCA Conundrum