From Time is brain to Physiology is brain: a case for reflection in acute stroke treatment decisions

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http://brain.oxfordjournals.org/content/138/7/1768

Smriti Agarwal , Elizabeth A. Warburton , Jean-Claude Baron

DOI: http://dx.doi.org/10.1093/brain/awv120 1768-1770 First published online: 23 June 2015

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This scientific commentary refers to ‘Perfusion computed tomography to assist decision making for stroke thrombolysis’, by Bivard et al. (doi:10.1093/brain/awv071).

The ischaemic penumbra, defined as severely hypoperfused, functionally impaired yet salvageable tissue, has been established as the key target for acute stroke therapy for more than three decades (Muir et al., 2006). However, the penumbra has a limited lifespan and, unless reperfused early, it progresses to become part of the irreversibly damaged tissue referred to as the ‘core’. The core therefore grows over time, incorporating first the most hypoperfused portions of the penumbra, and then progressively less hypoperfused portions, until none remains. How fast this process occurs varies greatly from subject to subject, mainly because of variable pial collaterals and the occurrence of spontaneous reperfusion (Fig. 1). On a mechanistic basis, reperfusion therapy—such as with intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA)—would be expected to be of no benefit, and potentially harmful, in cases with large core or no penumbra (Marchal et al., 1993).

Figure 1

The three main pathophysiological profiles used by Bivard et al. to categorize acute stroke patients, as originally defined using PET with ¹⁵oxygen-labelled compounds to generate quantitative maps of cerebral blood flow (CBF, left column) and the cerebral oxygen metabolic rate (CMRO₂, right). Validated tissue compartments including penumbra (reduced cerebral blood flow but relatively preserved CMRO₂) and core (markedly reduced CMRO₂) were used to characterize the three profiles of ‘target mismatch', ‘large core' and ‘no mismatch' (Muir et al., 2006). Consistent with the strikingly distinct spontaneous outcomes associated with these profiles (Marchal et al., 1993), Bivard et al. provide evidence from their cohort that the target mismatch group, i.e. patients with significant penumbral tissue and a small core, benefit the most from intravenous …