Alejandro Fuerte, MD
Desai SM, Rocha M, Jovin TG, Jadhav AP. High Variability in Neuronal Loss: Time Is Brain, Requantified. Stroke. 2018;50:34–37
Acute ischemic stroke caused because of large-vessel occlusion (LVO) is a neurological emergency characterized by abrupt interruption in blood flow that causes rapid neuronal death. It has been shown that time in this situation is directly proportional to the infarcted brain tissue. In this context, there is an approximate loss of 1.9 million neurons every minute, which means “run!”. However, as we have observed in the DAWN and DEFUSE 3 trials, there is inter-individual variability, and the therapeutic window can be widened in those cases of patients whose ischemic core grows slowly.
The main goal of Desai et al. was to calculate the rate of loss of brain tissue within a cross-section of LVO patients with different infarct growth rate (IGR). For this purpose, they performed a retrospective review of a prospectively acquired database of acute ischemic strokes with occlusion of the internal carotid artery or middle cerebral artery. Ischemic core volume was measured with automated software and time from last known well to imaging was recorded. For the final calculations, they used what is already known about the volume of forebrain (total number of neurons, synapses, and myelinated fiber length) and, with the results, a statistical analysis was performed.
From the total number of patients collected during the study period (2667), advanced imaging for ischemic core was only available in 185 cases. 56% of these patients had witnessed stroke onset. Regardless of whether the clinical onset was witnessed or not, rate of neuron loss ranges from <35100 to >26.6 million per minute with the majority of LVO strokes having a rate of neuron loss of <1 million per minute (mean and median of 2 million and 0.9 million, respectively).
The results of this study are in accordance with what was previously reported on neuronal loss in ischemic stroke. As a novel finding, it has been discovered that high variability in the rate of neurons lost per minute exists, from <35000 to >27 million, from negligible to almost 14× the previously published average rate of neuron loss.
In view of the results, the authors conclude that there are, indeed, fast and slow progressors of infarct growth, and that this seems to be related to the status of collateral circulation. This explains, as observed in the DAWN and DEFUSE 3 trials, that there are patients who may benefit from late reperfusion therapies by belonging to the group of slow progressors. For this reason, the need for advanced imaging for ischemic core (computed tomography perfusion or magnetic resonance imaging diffusion weighted imaging) is emphasized to identify such patients outside the early-time window (0 to 6 hours), context in which their usefulness is questioned.