Q&A with Dr. Simpkins
Stroke Progress and Innovation Awards 2016
Alexis N. Simpkins, MD, PhD
Alexis N. Simpkins, Christian Dias, Richard Leigh, on behalf of the National Institutes of Health Natural History of Stroke Investigators
SPOTLIGHT: Q&A with Dr. Simpkins
What is the key take-away message from your article?
In this paper we demonstrate 2 key points. First, mild diffuse blood brain barrier disruption occurring during acute cerebral ischemia is reversible in the context of early reperfusion. Second, unlike mild diffuse blood brain barrier disruption, severe focal blood brain barrier disruption is indicative of blood brain barrier rupture and associated with subsequent intracerebral hemorrhage after acute treatment.
What prompted you and your co-authors to perform this study?
Prior studies had demonstrated the association between blood brain barrier disruption and hemorrhagic transformation. However, this study was prompted by the observation that, in some patients, BBB disruption appeared to reverse with reperfusion and was not associated with hemorrhagic transformation. There was a dramatic demonstration of this phenomenon in one patient who we treated in the course of an earlier study. Such a finding was consistent with animal models of acute stroke, but had not been demonstrated in humans. This led us to design our study to address the question, is BBB disruption reversible in humans?
What is innovative about this work? And what are its applications?
This work used a novel imaging methodology on a unique dataset to ask a question that previously could not have been addressed in humans. The BBB permeability maps used in this study were generated from an MRI sequence typically collected in stroke patients to assess blood flow. Combing this methodology with the NIH Natural History of Stroke dataset, which collects serial MRI scans in acute stroke patients before and immediately after treatment, we were able to demonstrate not only that BBB disruption could be reversible, but also that diffuse reversible BBB disruption is distinct from focal severe BBB disruption that is associated with hemorrhagic transformation. It will be important to separate these two types of BBB disruption moving forward if BBB imaging is to be used in clinical decision making. Hopefully our findings will eventually lead to an expansion of the number of stroke patients we are able to safely treat.
Tell us about the biggest challenge you came across while conducting this study.
This study required patients to be screened with MRI prior to acute intervention with thrombolysis. This is a challenge for many centers. We have been able to overcome this challenge by having a very streamlined imaging protocol for managing acute stroke patients.
Is there anything more you would like to add about your work?
In addition to the clinical implications of our study, we are also interested in the mechanism behind the reversibility of the mild blood brain barrier disruption as well as what factors predict who will have focal severe blood brain barrier disruption. With this knowledge, we may be able to find a way to manipulate the blood brain barrier and facilitate new approaches to acute stroke treatment.
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