Ravinder-Jeet Singh, MBBS, DM
Broocks G, Rajput F, Hanning U, Faizy TD, Leischner H, Schön G, et al. Highest Lesion Growth Rates in Patients With Hyperacute Stroke: When Time Is Brain Particularly Matters. Stroke. 2018;50:189–192.
Infarct growth has become a topic of intense discussion in the current endovascular era, mainly due to its likely impact on stroke care models. A core theme of these models is decision to transport or treat eligible patients immediately, but also to limit futile transfers (drip-and-ship patient) and futile recanalization (mothership patient). The big question is: Which patient will grow their infarct during transfer and thus become ineligible for intervention on arrival to a comprehensive stroke center (futile transfers), and who will grow their infarct after imaging to derive no or minimal benefit from recanalization (futile recanalization)? Various clinical and imaging predictors have been proposed to predict infarct growth, including age, time, collateral status, etc. The study by Broocks et al. suggests that time is an important determinant of infarct growth, but its relation to lesion growth is rather counterintuitive, with early presenters having higher infarct growth compared to late presenters.
The authors enrolled patients with M1 middle cerebral artery occlusion presenting within 6 hours from symptoms onset who were successfully recanalized (TICI 2b/c flow) using endovascular thrombectomy. The cohort (N=51) was divided into hyperacute (<1.85 hours; n=25) and acute presenters (≥1.85 hours; n=26) based on onset to imaging time. Both groups had similar imaging to recanalization time (median, 2.7 versus 2.4 hours; P=0.40). The difference in infarct size, measured on ASPECTS and volumetrically, was compared between hyperacutely and acutely presenting subjects. The mean ASPECT difference (24 hours minus baseline) was 2.7 vs 1.6 (P=0.04) between hyperacutely and acutely presenting patients, while mean volumetric difference was 26.6 vs 17.3 ml (P=0.355 for mean difference; P=0.04 for variance of growth). The authors conclude that lesion growth between imaging and recanalization was higher in patients presenting in a hyperacute time window and could be a sign of a distinctive infarct dynamic in this time window.
However, there are several limitations to the study. First, despite similar ASPECTS and lesion volume at baseline and also similar CT to recanalization time, the two groups had different final infarct volumes suggesting that most infarct growth occurred after imaging. If most infarct growth occurs early (as per the authors), then hyperacute presenters should have had lower ASPECTS and higher infarct volumes at baseline. Second, volumetric lesion growth was not statistically significant, though the authors subsequently used Levene’s test to show increased variance; however, this could be driven by small sample size of the group. Third, CT perfusion derived core estimation (used in the study) could be imprecise, especially when complete recanalization is achieved. Finally, collateral status was neither described nor tested in the multivariable model. Collateral is an important modifier of tissue-time relationship and therefore could explain the variability of infarct volumes instead of time; for example, if early presenters had poor collaterals, then they would have larger infarct growth. The study reiterates the “time is brain” concept, but larger well-designed studies are required to identify patients who are rapid vs slow infarct growers (or progressors).
It is important to realize that the actual purpose of this paper was to investigate whether the same time from imaging to recanalization results in different lesion growth dependent on time window (based on previously proposed nonlinear, logarithmic lesion growth rates in acute stroke).
The main message is: in the hyperacute time window there is even more (tissue) to lose
There is diverging literature on pattern of infarct growth based on ischemic stroke models and observational human data. Newer evidence favors logarithmic growth, however, slope varies widely. This could be explained by the degree of collateral flow and also the presence of any residual antegrade flow through permeable clots.The impact of collateral grade on dynamics of infarct growth was elegantly demostrated in an experiment by Christoforidis et al (http://www.ajnr.org/content/38/2/270). The growth assumes more linear shape at higher collateral grades and logarithmic at lower collateral grades. Therefore, presence and robustness of penumbral blood flow and intrinsic vulnerability of the penumbral tissue (eg. grey vs white matter) determine the pattern of infarct growth. In addition, many other factors could act and further modify the infarct growth rates and patterns, for example blood glucose, ischemic preconditioning etc. Finally, effective recanalization can change the equation at any time point.Thus, the relation of infarct volume to time is highly variable and modifiable by several factors as mentioned.