Reperfusion Beyond 6 Hours Reduces Infarct Probability in Moderately Ischemic Brain Tissue

So from this could we calculate the death rate of neurons during the week or so that the neuronal cascade of death is occurring? We never will solve that problem unless we can quantify the neurons dying per minute. 1.9 million neurons dying per minute in stroke focused attention on speed of intervention. 
http://stroke.ahajournals.org/content/47/1/99.abstract?sid=9902c2fc-fc05-40fb-b6dc-2e313e0096c5

1. Hongyu An, DSc*;
2. Andria L. Ford, MD*;
3. Cihat Eldeniz, PhD;
4. Yasheng Chen, DSc;
5. Katie D. Vo, MD;
6. Hongtu Zhu, PhD;
7. William J. Powers, MD;
8. Weili Lin, PhD;
9. Jin-Moo Lee, MD, PhD

+ Author Affiliations

1. From the Mallinckrodt Institute of Radiology (H.A., C.E., K.D.V., J.-M.L.) and Department of Neurology (A.L.F., Y.C., J.-M.L.), Washington University, School of Medicine; and Department of Biostatistics (H.Z.), Department of Neurology (W.J.P., W.L.), and Department of Radiology (W.L.), University of North Carolina at Chapel Hill.

1. Correspondence to Jin-Moo Lee, MD, Washington University, School of Medicine, Department of Neurology, 600 South Euclid Ave, Campus Box 8111, Saint Louis, Missouri 63110, E-mail leejm@neuro.wustl.edu or Weili Lin, PhD, University of North Carolina, 106 Mason Farm Rd, Campus Box 7515, Chapel Hill, NC 27599, E-mail weili_lin@med.unc.edu

1. ↵* Drs An and Ford contributed equally.

Abstract

Background and Purpose—We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome.

Methods—Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT–[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp_{3 h}), 6 (MTTp_{6 h}), and 24 hours (MTTp_{24 h}). Perfusion changes between 3 and 6 hours (ΔMTTp_{3_6}) and 6 and 24 hours (ΔMTTp_{6_24}) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp_{3_6} and ΔMTTp_{6_24} on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp_{3 h}, ΔMTTp_{3_6}, and ΔMTT_{6_24} as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether ΔMTTp_{3_6} and ΔMTT_{6_24} had significant impact on tissue fate for varying severities of baseline perfusion.

Results—Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. ΔMTT_{3_6} significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0–15 s). ΔMTT_{6_24} also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0–10 s).

Conclusions—Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows.