A conversation with Raul Nogueira, MD, Professor of Neurology, Neurosurgery and Radiology,Emory University School of Medicine, Director of Neuroendovascular Service, Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, on endovascular thrombectomy for acute ischemic stroke with mild symptoms.
Interviewed by Mark R. Etherton, MD, PhD, Assistant in Neurology, Massachusetts General Hospital, Instructor, Harvard Medical School.
They will be discussing the paper “Mechanical Thrombectomy in Patients With Milder Strokes and Large Vessel Occlusions: A Multicenter Matched Analysis,” published in the October 2018 issue of Stroke.
Dr. Etherton: This is a very interesting paper that I think raises some good questions about the triage and management approaches to patients with large vessel occlusions and low severity ischemic strokes as assessed with the NIHSS. Could you speak a little bit regarding your management approaches to this patient population, including if any differences whether the stroke was involving the anterior or posterior circulation?
Dr. Nogueira: The first thing you have to acknowledge is there is not a lot of data to answer this question. The data is mostly retrospective in nature. There are methodological issues with these retrospective approaches in that you have to analyze them as intention-to-treat. So you have to separate out the cohorts as immediate treatment versus no immediate treatment. In reality, you really have three groups: immediate mechanical thrombectomy (MT), immediate medical therapy, and immediate medical therapy with subsequent deterioration and rescue MT. You cannot group this last group with the MT group because your initial intent was to treat this group medically. This is the equivalent of cross-over in a clinical trial which creates methodological problems.
There is one single prospective dataset that we’ve been collecting at Emory analyzing patients with low NIHSS selected for MT; however, it is not randomized and there are many inherent biases in why these patients were taken for MT. At this point we can’t really say what is the right approach. Furthermore, we should acknowledge that the treatment effect size could be very small in this population since the control group has high likelihood of doing well. Moreover, this is a patient population that you cannot afford to have a complication given their mild presenting disability; however, they probably have a smaller core and lower likelihood of spontaneous ICH. Having said that, these are probably “slow progressors” in which you can take more time to approach the patient, access the lesion, talk with the family all as ways to increase the safety of the procedure. Cases like these are examples of wanting to be more precise than fast in the diagnostic and therapeutic approach. But we don’t really know if there is a strong benefit. We have 3–4 papers that suggest there may be a benefit; however, there are other papers that refute this possibility.
There are four factors that I look into when I am evaluating these patients:
- Is the patient fluctuating (i.e., NIHSS 14 initially, but now 4)? If so, this raises concern that the collateral status is not stable and that could be a bad sign.
- The second sign is auto-hypertension. For example, NIHSS 4, but BP 210/100 mmHg. What is going to happen when the patient can no longer support that blood pressure?
- This is my favorite point, the “stress test”. We sit the patient upright for 10–20 minutes and observe for any deterioration in the clinical exam. One can even see if that patient would tolerate walking. I think this is a very helpful test.
- The final point is perfusion imaging. If there is a big perfusion mismatch, this would make us more inclined to treat. It is important to note that normal perfusion does not necessarily indicate the patient is not at risk for deterioration as the scan is just a snapshot on time in a highly dynamic process.
But, in general, we explain to the family that this is a bit of an uncharted territory. More and more, we feel it is reasonable to open these vessels, so we give the option to the families very frequently. Lastly, a caveat would be if the LVO is secondary to ICAD, we are more conservative as the procedure is more complex and likely riskier.
Dr. Etherton: At a comprehensive stroke center, we have a bit of a luxury in that we can rapidly obtain CTA or even MRI/MRA to exonerate large vessel occlusion in patients with mild strokes. Based on this paper, what would be your advice for LVO screening in the community setting or facilities where rapid CTA/MRA are not as easily accomplished?
Dr. Nogueira: Another good question. The first thing to state is that in this age and time, we should be striving to make a mandate for early vascular imaging in all stroke patients including TIAs. Neurovascular imaging is a must for all stroke cases, so why not pursue neurovascular imaging earlier when it matters the most in terms of triaging the patient? I really think we as stroke neurologists need to put pressure on early vascular imaging as a mandate and definitely a metric for Primary Stroke Center certification. The vast majority of strokes, roughly 2/3 of all strokes, have NIHSS between 0 and 5 if I recall correctly. But 10–20% of low NIHSS have LVO, so this is a common problem. If you have an LVO, your chances of subsequent deterioration are 10-fold higher. We need to know who these patients are when they come to the Primary Stroke Center. We as a field have to start mandating acute imaging.
Dr. Etherton: This paper re-demonstrates that endovascular thrombectomy is relatively safe and, in comparison to the initial medical management group, efficacious. Do you think a prospective, randomized controlled trial is necessary and feasible to adequately address this question?
Dr. Nogueira: Absolutely. In fact, there are two trials. ENDOLOW, which is an RCT looking at immediate thrombectomy vs immediate medical therapy +/- tPA if desirable. NIHSS 0-5. ICA, M1 and large M2 occlusion. This should start before this summer. It will be enrolling in the U.S., Canada, Germany and Sweden. The second trial IN EXTREMIS has two sub-studies: a large core and a low NIHSS (NIHSS < 6 and LVO occlusion), which is very similar to ENDOLOW, and should also start soon. Hopefully, in the next 2–3 years, we will have answers for how to best manage these patients.
Dr. Etherton: Last question. How would this question change regarding patients in the late window for EVT?
Dr. Nogueira: Another great question. One would think that if a patient has a low NIHSS with low fluctuation for a longer period of time that the chances are they will be more stable than a patient that hasn’t demonstrated they can support the collaterals for that period of time. We tend to get more conservative as the time from onset is extended. The likelihood of deterioration probably declines over time. One would think from simple physiology that the longer you are stable, the lower your chances of deterioration. In the ENDOLOW trial, we will look into this a bit as we are randomizing all the way to 24 hours, stratified for time.
Dr. Etherton: Thank you very much.