Kat Dakay, DO 

Saber H, Narayanan S, Palla M, Saver JL, Nogueira RG, Yoo AJ, et al. Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: a meta-analysis. J Neurointerv Surg. 2018

While the data is more straightforward on the benefit of treating proximal large vessel occlusions such as the M1 or the internal carotid artery with mechanical thrombectomy, M2’s are less certain. The endovascular trials published in 2014 underrepresented M2 occlusions: SWIFT PRIME, ESCAPE and REVASCAT excluded M2 occlusions, whereas MR CLEAN and EXTEND IA had a few M2 occlusions included in their study populations [1].

The concerns about potential risks of treating M2 occlusions are understandable: M2 occlusions would theoretically have less penumbral tissue compared to M1 occlusions, and they may be more likely than proximal occlusions to recanalize with IV tPA [2]. There is a concern about procedural risks as well: Some believe that the narrow lumen diameter and thinner vessel wall may predispose to procedural complications [3]. On the other hand, the recanalization effect of tPA may be overestimated, with one series only demonstrating 6% recanalization with tPA alone [4]. Additionally, the natural history of M2 occlusions can be debilitating, with two retrospective studies of untreated patients showing that about half of patients being functionally dependent [5, 6] with even worse outcomes occurring in left M2 occlusions.

However, there is no clear consensus on treating M2 large vessel occlusions. Some advocate treating patients with severe symptoms [7] or patients in whom tPA is contraindicated [4]. While there is a paucity of randomized controlled data relating to M2 occlusions, there may be some lessons to be gleaned from retrospective studies reported in the literature.

Saber and coauthors [8] have performed a meta-analysis of twelve studies relating to M2 occlusions. They included studies in which 10 or more M2 occlusions were treated with second-generation endovascular devices; the twelve studies contained a total of 1080 patients.

In all, 59% of M2 occlusions treated endovascularly achieved functional independence. The recanalization rates were high at 81%. Mortality was 16%, with a symptomatic ICH rate of 10%. Patients who underwent MT with successful recanalization (TICI 2b-3) were more likely to achieve functional independence than those who had poor recanalization (TICI 0-2a); the mode of treatment (clot aspiration versus stent retriever) did not matter in terms of functional outcome or extent of recanalization. Notably, the outcomes for M2 occlusions were overall significantly better than M1 occlusions; however, the sICH rate was significantly higher in M2 occlusions compared to M1 (15% vs. 4.7%, p<0.001). All in all, the authors note that mechanical thrombectomy in M2 occlusions which are safely accessible can be associated with similar outcomes to M1 occlusions, despite the higher sICH rate, and that these outcome statistics are similar to those which led to the guidelines for M1 thrombectomy. However, the retrospective nature of most of the included studies limits the analysis somewhat, as patient selection may have confounded the results.

Another limitation of the meta-analysis is that we don’t have data on patients who were treated medically with tPA alone. One study published in JAMA Neurology did compare medically treated M2’s with endovascularly treated M2’s at ten participating centers, and found that the endovascularly treated patients had a significantly higher likelihood of functional independence  as compared to medically treated patients, in spite of a higher rate of sICH [1]. However, this study was also retrospective, with heterogeneity in selection of patients for MT versus medical management, in most cases at the discretion of the treating physician; it is possible that cases which were felt to be lower risk and highest likelihood of benefit were selected for MT, causing selection bias. However, the similarity of these results to the meta-analysis is suggestive that there may be a benefit to MT.

This study underscores the need for further research regarding M2 occlusions. In a recent podcast, Dr. Ansaar Rai proposed the idea of a large, nationwide registry of ELVOs including M2 occlusions to help further elucidate the benefits and potential complications of MT [9]. This would be helpful, as many published studies are single-center series and subject to selection bias; while this is an inherent issue with retrospective research, the inclusion of multiple centers and a larger population of patients may help point towards important trends in the data. One takeaway from the meta-analysis is that the incidence of sICH should be taken into context with the potential benefits of recanalization and its effect on the overall outcome of the patient.

References:

  1. Sarraj A, Sangha N, Hussain MS, Wisco D, Vora N, Elijovich L, et al. Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery m2 segment. JAMA Neurol. 2016;73:1291-1296
  2. Salahuddin H, Ramaiah G, Slawski DE, Shawver J, Buehler M, Zaidi SF, et al. Mechanical thrombectomy of m1 and m2 middle cerebral artery occlusions. J Neurointerv Surg. 2018;10:330-334
  3. Kim YW, Son S, Kang DH, Hwang YH, Kim YS. Endovascular thrombectomy for m2 occlusions: Comparison between forced arterial suction thrombectomy and stent retriever thrombectomy. J Neurointerv Surg. 2017;9:626-630
  4. Sheth SA, Yoo B, Saver JL, Starkman S, Ali LK, Kim D, et al. M2 occlusions as targets for endovascular therapy: Comprehensive analysis of diffusion/perfusion mri, angiography, and clinical outcomes. J Neurointerv Surg. 2015;7:478-483
  5. Hernandez-Perez M, Perez de la Ossa N, Aleu A, Millan M, Gomis M, Dorado L, et al. Natural history of acute stroke due to occlusion of the middle cerebral artery and intracranial internal carotid artery. J Neuroimaging. 2014;24:354-358
  6. Lima FO, Furie KL, Silva GS, Lev MH, Camargo EC, Singhal AB, et al. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol. 2014;71:151-157
  7. Dorn F, Lockau H, Stetefeld H, Kabbasch C, Kraus B, Dohmen C, et al. Mechanical thrombectomy of m2-occlusion. J Stroke Cerebrovasc Dis. 2015;24:1465-1470
  8. Saber H, Narayanan S, Palla M, Saver JL, Nogueira RG, Yoo AJ, et al. Mechanical thrombectomy for acute ischemic stroke with occlusion of the m2 segment of the middle cerebral artery: A meta-analysis. J Neurointerv Surg. 2018;10:620-624
  9. Surgery JoN. “M2 occlusions patients may benefit from endovascular therapy.” JNIS Podcast. 2018