Robert W. Regenhardt, MD, PhD
For large vessel occlusion (LVO) strokes, endovascular thrombectomy (ET) has become the standard of care. Given the demonstrated efficacy and low number needed to treat for this powerful therapy, there is impetus to push the envelope on inclusion criteria. In terms of time, the recent DAWN and DEFUSE 3 trials have prompted most institutions to consider patients up to 24 hours since last seen well. In addition to pushing the time window, others are investigating the safety and efficacy of targeting vessels that are smaller and more distal than the carotid and proximal middle cerebral arteries (MCA). Indeed, some distal occlusions can result in significant neurologic deficits, especially if they are upstream of eloquent cortex such as distal MCA occlusions resulting in aphasia. Moreover, newer devices allow interventionalists access to these smaller distal vessels. Several studies have suggested a benefit of M2 segment ET, showing improved outcomes and similar rates of reperfusion. However, a large meta-analysis of 1080 patients with M2 occlusions showed there was an increased risk of hemorrhage compared to M1 occlusions.
This study by Grossberg et al published in the July issue of Stroke sought to examine the safety and efficacy of distal ET at their single center. Retrospectively, they identified 69 patients with distal occlusions treated with ET from 2010-2015. They defined distal occlusions as involving anterior cerebral arteries (ACA), posterior cerebral arteries (PCA), or MCA distal to the M3 opercular segment. 42% received intravenous (IV) tPA, and the median NIHSS score was 18. For 45 patients, the distal occlusion was the primary treatment; for 23 patients, the distal occlusion was a rescue treatment after a different primary LVO. Primary treatments were of the M3 (n=21), ACA (n=8), ACA and M1/M2 (n=10), ACA and M3 (n=3), and PCA (n=3). Rescue treatments were of the M3 (n=11), ACA (n=7), PCA (n=4), and M3 and ACA (n=1).
Treatment approaches included stent-retrievers (54%), thromboaspiration (45%), and intra-arterial tPA (52%). Complete or near complete reperfusion (mTICI 2b-3) was obtained in 83% overall, including 74% of thromboaspiration cases and, interestingly, 92% of stent-retriever cases. Furthermore, mTICI 2b-3 was obtained in 90% of cases involving the ACA and 65% involving the MCA. There was a 7% rate of parenchymal hemorrhage (within the 2-8% range found in the 2015 landmark trials). Only three patients (4%) had hemorrhage in the territory of their distal occlusions (one PCA and two M3 occlusions). All three achieved mTICI 3, and two received IV tPA. Of all 69 patients, no vessel perforation was noted and no cases of distal ET resulted in a more proximal occlusion. At 90 days, 30% had good outcomes (mRS 0-2) and 20% died.
The authors conclude that distal vessel occlusions may be treated with ET safely and effectively, while acknowledging that large randomized trials are still necessary. However, this is a difficult patient population to study, given the heterogenous clinical presentations and the different sizes and locations of vessels involved. Patient selection will be key. For this present study, the authors included patients based on “clinical symptoms and neuroimaging data about the viability and eloquence of involved territories.” They point out that their series contains more severe strokes than expected for distal occlusions, reflecting selection bias as the more severe patients would be more likely considered for ET. Many additional cases were rescue ET for intraprocedural distal embolization. The authors point out that the rate of embolization to the ACA has been cited at 4-11%, and there will be more need for rescue therapy as more patients are undergoing ET with the 24-hour window. A caveat here is the development of new techniques, such as CAPTIVE (continuous aspiration before intracranial vascular embolectomy), that may prevent distal embolization in the first place. Other cases in this present study were severe strokes that involved multiple vascular territories which compromised collateral flow.
In their discussion, the authors recommend careful risk-benefit assessment. They warn that distal arteries are smaller in caliber, have thinner walls, and are typically more tortuous. Moreover, these distal vessel occlusions may be difficult to detect without invasive conventional angiography, further complicating patient selection. That stated, ET may be considered when a distal vessel occlusion is identified, eloquent cortex is involved, there is disabling clinical deficit, there is significant penumbra at risk, there are poor collaterals, and when there is minimal improvement after proximal reperfusion.
Once patients are selected, there are also varying treatment approaches available, including stent-retriever, thromboaspiration, and intra-arterial tPA. This study suggests that stent-retrievers may yield the best reperfusion rates. The authors state the approach was “at the discretion of the treating neurointerventionalist depending on vessel size and location as well as the degree of vascular tortuosity.” They suggest avoiding ET and favoring intra-arterial tPA in distal superior division branches of the MCA given their greater tortuosity. Another consideration is that the natural history of distal vessel occlusions is one of a better prognosis compared to more proximal lesions. One should consider that perhaps IV tPA alone is “enough,” as it is well understood to be more effective for distal occlusions compared to proximal ones. However, there may be patients who are not eligible for IV tPA but could still benefit from ET. As the authors point out, there is a paucity of randomized data for ET in these vessels, where IMS-III included only 5 and MR CLEAN included only 3.
Indeed, the next step is the organization of a large multi-center randomized trial. As mentioned, the difficulty in patient selection and treatment approach selection will make this an arduous task. Furthermore, concerns of smaller effect size in distal ET may necessitate a large sample size to demonstrate treatment effect. Until that time, distal occlusions may best be treated on a case-by-case basis after careful discussions between vascular neurologists, neurointerventionalists, and neuroradiologists.