Time and Diffusion Lesion Size in Major Anterior Circulation Ischemic Strokes

Acute ischemic stroke is the fourth leading cause of death in the United States and the leading cause of severe disability in adults. Cerebral artery occlusions of the terminal internal carotid artery (ICA) and the proximal middle cerebral artery (MCA) represent 30% to 40% of all acute ischemic strokes, but account for the majority of poor outcomes. Current treatment approaches for these strokes are commonly restricted by the time elapsed since stroke onset. For intravenous tissue-type plasminogen activator, the currently approved treatment window is 3 to 4.5 hours from the time of stroke onset. For intra-arterial therapy, the time window is typically 0 to 6 hours for thrombolysis and 0 to 8 hours for mechanical therapies. This adherence to time windows is driven by the idea that there is rapid infarct growth while ischemia is left untreated and that treatment efficacy rapidly decreases with time. A limitation of the current approach is that it does not take into consideration patient-specific cerebrovascular physiology. Although quantitative estimates of the pace of neuronal loss in human ischemic stroke may be applicable on a population level, the actual rate of neuronal loss in patients with proximal anterior circulation artery occlusion strokes may vary considerably from patient to patient and is influenced by several factors, most importantly the effectiveness of cerebral perfusion via the collateral circulation in maintaining the reversibly threatened, hypoperfused but still viable tissue outside of the infarct. Recently, the time-based approach has been challenged because treatments have been shown to be effective outside the traditional time windows. The dynamics of infarct growth in patients with proximal anterior circulation artery occlusion strokes are not well documented. Experimental animal stroke models suggest that the most common pattern of infarct growth is logarithmic. Although infarct growth patterns in human brain have not specifically been evaluated, linear infarct growth is commonly assumed. The purpose of this study was to gain insights into Background and Purpose—Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. Methods—Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. Results—Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. Conclusions—Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows. (Stroke. 2014;45:2936-2941.)