Better Late than Never: Mechanical Thrombectomy in Late-Presenting Ischemic Stroke

Case: At 8AM, EMS brings in a 72-year-old man with a history of CAD, HTN, and DM who is having difficulty speaking. His family notes that his symptoms began the previous evening around 8PM (12 hours ago). On exam the patient has HR 82, BP 130/80, right facial droop, and weakness in the right arm. Glucose is 120. Head CT shows no hemorrhage, but CTA shows proximal left MCA occlusion.

Clinical Question: What is the role of mechanical thrombectomy in late-presenting ischemic stroke?

Summary of Evidence:

• Ischemic stroke is a major cause of morbidity and mortality worldwide. Traditional standard of care for ischemic stroke involves giving thrombolytics (tPA) within 3 to 4.5 hours of symptom onset in eligible patients and utilizing mechanical thrombectomy within 6 hours of symptom onset in patients with large artery occlusion. (1-2)

• New evidence from the DEFUSE 3 and DAWN trials suggest that patients with ischemic strokes of the proximal MCA or internal carotid artery presenting within 6 to 16 or 24 hours may also benefit from mechanical thrombectomy. (3-4)

• Diffusion-weighted MRI and CT perfusion imaging were utilized in these studies to identify patients with areas of ischemic brain tissue that could be potentially salvaged with mechanical thrombectomy. CT perfusion imaging is a relatively new concept that will likely be increasingly used in the evaluation of stroke patients due to its wider availability, lower cost, and faster results compared to diffusion-weighted MRI. (1-2,5)

• CT perfusion imaging quantifies how contrast flows through capillary vessels via sequential spiral CT scanning. Although the interpretation of these scans is complex and automated software is often utilized, it is useful to have a general approach to interpret these images in real time. (2,5)

• Ischemic tissue can be identified by increased mean transit time (MTT), which is the average time it takes blood to flow through a given brain region. Mean transit time is higher in ischemic tissue because autoregulatory mechanisms cause vasodilation in response to decreased perfusion. Infarcted tissue, on the other hand, is identified by reduced cerebral blood volume (CBV), which is the total volume of blood in a given volume of brain. Cerebral blood volume is low in infarcted tissue because there is failure of autoregulation and therefore failure of vasodilation. (2,5)

• The volume of ischemic, but not yet infarcted, tissue is known as the penumbra. The penumbra represents ischemic tissue that can be potentially salvaged with mechanical thrombectomy. The larger the penumbra, the more likely a patient will benefit from thrombectomy. (1-2)

• This concept is illustrated below. The patient in the top row of the figure has a left MCA occlusion with a roughly equal volume of infarct and ischemia. This indicates that nearly all tissue with compromised blood flow is already dead and therefore thrombectomy is not indicated. The patient in the lower row, however, has a small infarct surrounded by a large area of ischemia. With thrombectomy, it may be possible to restore blood flow to this ischemic area and prevent infarction.

• The DAWN and DEFUSE 3 trials, both published in 2018, demonstrate the utility of these advances in neuroimaging in identifying patients who are likely to benefit from mechanical thrombectomy greater than 6 hours after symptom onset. General inclusion criteria for both trials included age >18, minimal prestroke disability, no intracranial hemorrhage, and occlusion of the internal carotid artery or proximal MCA. (3-4)

• DAWN – Forty-nine percent of 107 patients who received thrombectomy and medical management within 6 to 24 hours of symptom onset were functionally independent (Modified Rankin Score of ≤2) at 90 days compared to 13% with medical management alone. Inclusion criteria were NIH Stroke Scale deficit of ≥10, infarct involving <1/3 of MCA territory by CT perfusion or diffusion-weighted MRI, and a mismatch between severity of clinical deficit and infarct volume. (3)

• DEFUSE 3 – Forty-five percent of 92 patients who received thrombectomy and medical management within 6 to 16 hours of symptom onset were functionally independent (Modified Rankin Score of ≤2) at 90 days compared to 17% with medical management alone. Additionally, 90-day mortality for the thrombectomy group was 14% compared to 26% for the control group. Inclusion criteria were NIH Stroke Scale deficit of ≥6, infarct size <70 ml, penumbra >15 ml, and ratio of ischemic volume to infarct volume of >1.8. (4)

Recommendations:

• Mechanical thrombectomy has the potential to substantially increase functional independence and decrease mortality in late-presenting ischemic stroke patients. (3-4)

• In additional to standard medical management, mechanical thrombectomy should be considered for patients presenting with ischemic strokes of the proximal MCA or internal carotid artery within 6 to 24 hours of symptom onset. (3-4)

• CT perfusion scans, as well as diffusion-weighted MRI, are useful tests to identify patients eligible for mechanical thrombectomy. (2-6)

• Patients most likely to benefit from mechanical thrombectomy are those with a small core infarct volume compared to ischemic volume. (6)

• When interpreting CT perfusion imaging, cerebral blood flow (CBV) can be used to estimate core infarct volume, and mean transit time (MTT) can be used to estimate ischemic volume. The difference between these volumes represents potentially salvageable ischemic tissue, also known as the penumbra. (2)

• These recommendations are limited to ischemic strokes of the MCA or internal carotid artery. More research is needed to determine how broadly these principles can be applied to other types of ischemic strokes. (7)

Test your knowledge - The CT perfusion images for the patient in the case are shown below. Would you recommend mechanical thrombectomy for this patient? (answer below references)

References:

1. Campbell BC, Mitchell PJ, Kleinig TJ et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med . 2015;372(11):1009-1018.

2. Konstas AA, Goldmakher GV, Lee TY, Lev MH. Theoretic basis and technical implementations of CT perfusion in acute ischemic stroke, part 1: Theoretic basis. AJNR Am J Neuroradiol. 2009;30(4):662-8.

3. 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.

4. 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.

5. Vymazal J, Rulseh AM, Keller J, Janouskova L. Comparison of CT and MR imaging in ischemic stroke. Insights Imaging. 2012;3(6):619-27.

6. Bouslama M, Bowen MT, Haussen DC, et al. Selection Paradigms for Large Vessel Occlusion Acute Ischemic Stroke Endovascular Therapy. Cerebrovasc Dis. 2017;44(5-6):277-284.

7. Campbell BCV, Donnan GA, Lees KR, et al. Endovascular stent thrombectomy: the new standard of care for large vessel ischaemic stroke. Lancet Neurol. 2015;14(8):846-854.

Case answer – This patient presented with an ischemic stroke in the territory of the left MCA within 12 hours of symptom onset. Although this patient meets some inclusion criteria for the DAWN and DEFUSE 3 trials, thrombectomy would not be indicated because the volume of core infarct (shown by CBV) is almost equal in size to the volume of ischemia (shown by MTT). (2)