AJR January 2017

William T.C. Yuh Department of Radiology University of Washington

Revisit the Current Golden Rules in Managing Acute Ischemic Stroke and Explore a New Strategy to Further Improve Treatment Selection and Outcome

The authors reexamine the fundamental hypotheses from the imaging research on which clinical practices are based and reassess the current standard clinical and imaging strategies, or golden rules, established over decades for AIS.

1. Why is “penumbral imaging” for acute ischemic stroke (AIS) inconsistent and controversial among institutions and imaging experts?

As stated in the study, it is almost impossible to comprehensively address the complex and dynamic pathophysiology during an AIS particularly when “time is brain” remains the key strategy for the management of AIS. Different institutions and experts may have focused upon various aspects of the underlying pathophysiology designed for research and clinical translations. There have been more than 16,000 new imaging related studies published since 2011, thus AIS imaging protocols remain inconsistent and controversial among institutions and imaging experts. Such confusion can be readily appreciated by the quote of “Diffusion + Perfusion = Confusion” from residents and fellows. However, there are some fundamental principles and concepts that may demonstrate the potential limitations of the current imaging- and clinical-based golden rules. Therefore, this article is intended to cover only the potential limitations of established golden rules and to consider the potential for a “newer window of opportunity” to further improve the treatment selection and outcome.

2. What prompted you to do this study?

For decades, penumbral imaging has not reflected its diagnostic efficacy in AIS to substantially impact the treatment outcome. It has not been consistently included in the major clinical trials to guide treatment selection and demonstrate further improved outcome. The current imaging and clinical protocols (golden rules) have been the standard practice for decades, and the potential limits of the golden rules have not been “revisited.” Therefore, penumbra imaging, including DWI and perfusion-weighted imaging (PWI), may not have reached its potential, which motivated us to reevaluate the current standard clinical and imaging strategies, or golden rules, established over recent decades in the pursuit of more impactful imaging and clinical paradigms to further improve outcome.

3. What is the potential limitation of therapeutic window applying one-size-fits-all approaches to AIS patients?

The therapeutic window varies among individuals depending upon the severity of ischemic injury which is quantitatively defined by residual cerebral blood flow (CBF) to determine oligemia, penumbra (reversible ischemia) and infarction core (irreversible ischemia). The use of a fixed 6-hour window may exclude patients with reversible ischemia beyond 6 hours. This one-size-fits all approach may also include patients with irreversible ischemic core within 6 hours, when revascularization provides no benefit but increases the risk of hemorrhage. As such, therapeutic efficacy and outcomes may have been substantially underestimated by one-size-fits all approach. A more personalized therapeutic window which is not determined only by the time after onset may provide a new widow of opportunity for precision management of AIS, including no treatment (do no harm!).

4. Does the study have limitations that should be considered when reviewing the conclusion?

As stated in question 1 above, the complex and dynamic nature of AIS make it impossible to comprehensively address all the pathophysiological aspects in AIS, and therefore the article is focusing in identifying potential limitations of the golden rules. We do not have all the published results to support the clinical examples/scenarios, approaches, hypothesis and conclusions discussed in the article. It is our hope that the potential limitations of these golden rules may enhance the awareness and potential opportunity to further improve the management of AIS. (“A swallow does not mean spring, but a laughing horse is a laughing horse!)

5. What is the most important point information you learned in the study?

• The severity of ischemic injury differentiates among oligemia (no), ischemia (various degree), penumbra (lesser) and infarction core (severe), and therefore critically influences each individual’s therapeutic window and selection of treatment options. Prompt reperfusion intervention is only for penumbra but not for infarction core (contra-indication) and oligemia (no indication).
• Ischemia may include both penumbra and core, and therefore is not always indicative for prompt perfusion intervention.
• Oligemia, ischemia, penumbra and infarction core are quantitatively defined by residual CBF, not by imaging. Imaging based hypoperfusion abnormality has not quantitatively correlated and consistently validated with CBF, and may become positive during oligemia. Therefore penumbra imaging may not be able to consistently differentiate among oligemia, penumbra and infarction core, and thus improve treatment selection and outcome.

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