AIS due to MeVO: an evidence-based review

Dr. Fouzi Bala
Diagnostic and Interventional Neuroradiologist 
Tours Unversity Hospital
France

Medium vessel occlusion (MeVO) is the obstruction of a vessel with a lumen diameter between 0.75 and 2.00 mm. This occlusion type accounts for up to 40% of acute ischemic stroke.^1,2 MeVOs include M2-M4 middle cerebral artery (MCA), A2-A5 anterior cerebral artery (ACA), and P2-P5 posterior cerebral artery (PCA) segments. A1-ACA and P1-PCA segments,  superior cerebellar, anterior inferior cerebellar, and posterior inferior cerebellar arteries are not widely recognized as MeVOs.³

It is important to distinguish primary MeVOs from secondary MeVOs which usually result from migration of a thrombus to a distal location, either in the downstream territory or to a new territory.

How can we improve detection of MeVOs?

Contrary to large vessel occlusions (LVO), MeVOs affect small and distal vessels which make their detection challenging. Strategies such as perfusion imaging, and multiphase CT angiography may improve their detection rate.^4,5 Similarly, the high sensitivity of MRI for the detection of acute infarct and red blood cell-rich thrombi is useful to localize distal occlusions.

What is the natural history of MeVOs and the effect of intravenous thrombolysis?

Small and distal thrombi are associated with thrombolysis-induced recanalization, as it was shown in the INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). ⁶ However, only 21% and 47% of MeVOs patients achieve successful recanalization (revised arterial occlusive lesion score 2b/3) on follow-up CTA without and with intravenous alteplase, respectively, as it was reported in a pooled analysis of two prospective cohorts.⁷ At 90 days, only half of patients reached excellent outcomes (modified Ranskin Scale [mRS] 0-1) and 67% reached functional independence (mRS 0-2).⁷

Is tenecteplase more efficient than alteplase for MeVOs?

Tenecteplase is a second-generation thrombolytic, with greater fibrin specificity and prolonged half-life. Prior trials have reported higher recanalization rates compared to alteplase for large vessel occlusion and its effect seems to be stronger in distal occlusions.⁸ In a recent post-hoc analysis of the EXTEND-IA trials (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke), the authors reported higher reperfusion rates (initial TICI ≥2b) on the initial angiographic run of EVT in patients who received tenecteplase compared to alteplase (30% versus 10%) for distal M1 or M2 occlusions.⁹ Although these results are encouraging, the early reperfusion rate is still not high enough in these patients.

Is endovascular thrombectomy (EVT) safe and efficient in MeVOs?

Endovascular thrombectomy (EVT) trials published between 2015 and 2017 have included a small number of patients with MeVOs. In a substudy of the HERMES collaboration, 130 patients with M2-MCA occlusions were included, mostly proximal and dominant branches.¹⁰ Functional independence (mRS 0-2 at 90 days) was higher in the EVT group compared to best medical care (adjusted odds ratio 2.39, 95% CI 1.08 to 5.28), successful reperfusion was achieved in 59% of those who underwent EVT, and no symptomatic intracranial hemorrhage was seen in the EVT group.¹⁰ Regarding other MeVOs locations, two multicenter case-control studies of 243 patients (P2/P3 PCA occlusions) and 154 patients (A2/A3/A4 ACA occlusions) found similar safety and clinical outcomes of EVT compared to best medical treatment. That being said, superiority of EVT compared to best medical treatment in MeVOs has not been shown in a randomized clinical trial.

Ongoing trials of MeVO

High-level evidence supporting the safety and benefit of EVT in acute ischemic stroke due to MeVOs is not yet available. Four randomized clinical trials are ongoing and planning to include between 168 and 530 patients. All trials will include occlusions in the three arterial territories (MCA, ACA, and PCA). Functional outcome at 90 days is the primary outcome for all trials except one, which uses a composite outcome of successful reperfusion and symptomatic ICH. A summary of ongoing MeVOS trials is provided in the Table.

Table. Summary of Ongoing Medium Vessel Occlusion Trials.

Abbreviations: ACA: anterior cerebral artery, CTA: CT angiography, CTP: CT perfusion, DWI: diffusion-weighted imaging, MCA: middle cerebral artery, MRA: MR angiography, mRS: modified Rankin Scale, NIHSS: National Institutes of Health Stroke Scale, PCA: posterior cerebral artery, PWI: perfusion-weighted imaging  sICH: symptomatic intracranial hemorrhage.

Data in the table were extracted from https://clinicaltrials.gov  

References:

1. Goyal M, Ospel JM, Menon BK, Hill MD. MeVO: the next frontier? J Neurointerv Surg. 2020;12:545–547.
2. Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, Lobotesis K, Meila D, Meyer L, Raphaeli G, et al. Thrombectomy for Distal, Medium Vessel Occlusions: A Consensus Statement on Present Knowledge and Promising Directions. Stroke. 2020;51:2872–2884.
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4. McDonough RV, Qiu W, Ospel JM, Menon BK, Cimflova P, Goyal M. Multiphase CTA-derived tissue maps aid in detection of medium vessel occlusions. Neuroradiology. 2022;64:887–896.
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7. Ospel Johanna M., Menon Bijoy K., Demchuk Andrew M., Almekhlafi Mohammed A., Kashani Nima, Mayank Arnuv, Fainardi Enrico, Rubiera Marta, Khaw Alexander, Shankar Jai J., et al. Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020;51:3232–3240.
8. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378:1573–1582.
9. Yogendrakumar V, Churilov L, Guha P, Beharry J, Mitchell PJ, Kleinig TJ, Yassi N, Thijs V, Wu TY, Brown H, et al. Tenecteplase Treatment and Thrombus Characteristics Associated With Early Reperfusion: An EXTEND-IA TNK Trials Analysis. Stroke. 2023;54:706–714.
10. Menon BK, Hill MD, Davalos A, Roos YBWEM, Campbell BCV, Dippel DWJ, Guillemin F, Saver JL, Lugt A van der, Demchuk AM, et al. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. Journal of NeuroInterventional Surgery. 2019;11:1065–1069.