A 69-Year-Old Man Who Has Sustained an Acute, Observed Stroke

Correct Answer: B.

The readers must allow a few introductory words before getting to the data of substance of this case, because the featured patient is an authentic person and good friend of the author. I am old enough to remember the following scenario of a patient presenting with a documented acute myocardial infarction by the then-used " electrocardiogram and enzyme" criteria—troponins or cardiac catheterization were not used yet. Absolute bed rest for 21 days was the standard of care with an ultrahigh recurrence and mortality rate at 30 and 180 days. There was even a significant mortality rate among these patients from acute pulmonary embolism related to the bed rest. All the above seems hard to believe now but was true then. Then came cardiac catheterization and a myriad of techniques to extract, lyse, stent, and/or surgically bypass the causative coronary artery lesions to where we are now. Meanwhile, similarly, a patient presenting in the fashion to the presented case was easy to diagnose as a thrombotic cerebrovascular accident, but little more than scientific and wordy hand wringing was all we could do. Indeed, a variety of acute anticoagulation and antiplatelet regimens might decrease the feared and dreaded recurrence rates, but overall, the patient would be acutely confined to a hospital bed slowly "rehabilitated" as best possible; in a vast majority, he would be left with permanent and severe disability. This is not at all the case anymore, so let us proceed with a review and discussion of the amazing and genuinely exciting data regarding stroke management that has appeared in the past few years.

Using similar logic and knowledge of neurologic anatomy and physiology, it is now possible to essentially recapitulate the cardiology story with similar striking improvement in the management of patients with thrombotic stroke. The details regarding specific method of clot removal (lysis or thrombectomy), timing schemes, and their progressive lengthening of the efficacy/toxicity window for their use will follow. But before reviewing them, there needs to be commentary on the "theory" of efficacious clot removal. One can easily make the argument that the major advance in acute thrombotic cerebrovascular accident management has been radiologic, even more so than medical/surgical. In short, currently available computed tomography techniques, often using complex computer programs combined with advanced training in their interpretation, has resulted in being able to perform good patient selection by identifying a relatively small burden of brain tissue infarction (which will not reverse even if the thrombus is removed) but a large area of ischemic tissue at risk (termed penumbra, which can be reversed).^1,2 This ability also lessens the risk for hemorrhage when lytics are used and, thus, significantly enhances the benefit/risk ratio.^1,2

A specific example of this theory in action can be found in the study by Gregory Albers and colleagues.³ Patients were included in the study if their initial infarct volume core was less than 70 mL, their ratio volume of ischemic tissue to their initial infarct volume was 1.8 or more, and their absolute volume of potential reversible ischemia or penumbra was 15 mL or more.³ Essentially, all of the recent studies utilize some variant of this software image-processing system to evaluate the computed tomography perfusion and/or magnetic resonance imaging diffusion studies initially conducted on the patient.

There is also a series of 4 excellent randomized controlled trials utilizing the above theories. Henry Ma and colleagues⁴ found a 44% higher positive outcome associated with alteplase (a thrombolytic agent) compared with placebo. A total of 225 patients were treated 4.5 to 9 hours after the acute event, which was a doubling of the efficacy time window from the previous standard of care timing.⁴

Götz Thomella and colleagues⁵ went even further by demonstrating a favorable outcome in 53.3% of 246 patients taking alteplase compared with 41.8% of 244 patients taking placebo; patients had an unknown time of onset of stroke, and appropriate imaging criteria as described above.⁵ There was an increased complication of hemorrhage at 90 days (2.0% in the alteplase group  vs 0.4% in the placebo group), but this was not statistically significant and was more than overwhelmed by the significantly better functional outcome at 90 days.⁵ When mechanical thrombectomy is available, that modality may even be better, again with a very expanded timing window as long as the radiologic findings fit.

Gregory Albers and colleagues³ performed a randomized controlled trial with 182 patients and demonstrated a superior functional outcome when thrombectomy was performed (45%) vs standard medical therapy (17%), as well as a 90-day mortality benefit in the thrombectomy group (14%) vs the standard care group (26%).³ In this study, there was no excess in symptomatic cerebral hemorrhage (7% vs 4%).

In a similar randomized controlled trial, Raul Nogueira and colleagues⁶ extended the time window to 24 hours among 206 patients. Results demonstrated superior neurological outcomes and functional independence at 90 days with thrombectomy (49%) compared with controls (13%), again with no excess in hemorrhage or mortality.⁶

These trials are exciting and spectacular and confirm the efficacy and relative safety of these interventional techniques for acute thrombotic stroke and make answer B the optimal answer for management of the presented patient. The traditional medical regimens of antiplatelet agents (Answer A) or actual anticoagulation (Answer C), which may be incorrect as a “medical therapy” in any event, are incorrect choices here. Answer D, open craniotomy procedures, may have some role in selected patients with hemorrhagic stroke—intraparenchymal hemorrhage—but not the diagnosis here and is also incorrect.

Patient Follow-Up

The patient immediately underwent brain imaging using computerized software magnetic resonance imaging and computed tomography angiographic imaging, which demonstrated a thrombosis at the origin of the middle cerebral artery with core infarction size of 14 mL and ischemic penumbra size of 121 mL. He underwent endovascular mechanical thrombectomy and received alteplase with total resolution of occlusion and patent middle cerebral artery demonstrated at 24 hours. All neurologic deficits quickly resolved at 24 hours. He was discharged on the morning of hospital day 4. He subsequently underwent studies for the presence of hypercoagulable syndromes, as well as ambulatory Holter monitoring for occult atrial fibrillation. Results of the studies were negative. At 6 weeks, the patient is asymptomatic (Rankin score, 0) and taking a regimen of antiplatelet agents. He is back on the golf course and ball field with his pre-event (outstanding) skills intact.

Take Home Message

There is indeed an ongoing acute stroke care revolution¹ utilizing new computerized imaging techniques coupled with improved medical (alteplase thrombolytics) and endovascular surgical clot extraction thrombectomy techniques. The former enables clinicians to quite accurately assess and measure stroke size and the vital characteristics of site (large vessel occlusions or smaller), as well as assess the key findings of core infarction volume vs volume of salvageable brain tissue in the ischemic (but salvageable) brain tissue in the ischemic penumbra.² The latter enables clinicians to choose and execute appropriate medical (thrombolytics) and endovascular mechanical thrombectomy to address and correct these lesions—very akin to the cardiac catheter revolution to diagnose, lyse, and/or stent lesions in acute myocardial infarctions developed in the halcyon era of interventional cardiology 2 to 3 decades ago. All of this has resulted in dramatic improvements in stroke care, now shown to be very clinically meaningful and effective in stroke prognosis and functional recovery in increasingly more patients in an ever-expanding time window for the acute event.

References

1. Josephson SA, Kamel H. The acute stroke care revolution: enhancing access to therapeutic advances. JAMA. 2018;320(12):1239-1240. https://doi.org/10.1001/jama.2018.11122

2. Marshall RS. Image-guided intravenous alteplase for stroke - shattering a time window. N Engl J Med. 2019;380(19):1865-1866. https://doi.org/10.1056/nejme1904791

3. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-718. https://doi.org/10.1056/nejmoa1713973

4. Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-1803. https://doi.org/10.1056/nejmoa1813046

5. Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622. https://doi.org/10.1056/nejmoa1804355

6. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21. https://doi.org/10.1056/nejmoa1706442