Robert W. Regenhardt, MD, PhD

Tsang ACO, Orru E, Klostranec JM, Yang IH, Lau KK, Lau KK, et al. Thrombectomy outcomes of intracranial atherosclerosis-related occlusions: A systematic review and meta-analysis. Stroke. 2019; 50:1460–1466.

In the new era of endovascular thrombectomy (EVT) for large vessel occlusions (LVOs) up to 24 hours from symptom onset, focus has shifted to broadening patient selection and improving EVT technique. This manuscript sought to understand the unique features of EVT for a particular LVO etiology, intracranial atherosclerosis (ICAS). ICAS is less common than cardioembolism or carotid atheroembolism, making up about 6-8% of LVOs in Western populations and up to 25% in Asia. Owing in part to their decreased prevalence, ICAS-related LVOs are only recently being described as posing unique challenges to treatment. EVT may be less efficacious for these LVOs, and rescue treatments may be necessary given high re-occlusion rates.

The authors completed a systematic review and random-effect meta-analysis including articles that reported clinical features and outcomes for LVO secondary to ICAS vs. other etiologies. Of the 125 articles identified in the initial search from January 2010 to December 2018, 11 were ultimately eligible for inclusion (10 retrospective and 1 prospective). Ten studies were conducted in Asia, and 1 was in the United States. Five had predominantly anterior circulation LVO (>85%), and 3 had exclusively posterior circulation. Five had low risk of bias (Newcastle Ottawa scale), and 6 had moderate risk. Most variables reported had low heterogeneity (I2<50%), except for dyslipidemia, smoking, LVO location, thrombolysis, re-occlusion, final mTICI 2b/3, and puncture to reperfusion time.

The articles selected included 1,967 patients who underwent EVT, 496 with ICAS-related LVO and 1,471 with LVO from other etiologies. The ICAS patients were younger (64 vs. 67 years old), had lower baseline NIHSS (15 vs. 17), were more likely to be male (70 vs. 52%), had more hypertension (71 vs. 63%), more diabetes (32 vs 23%), more dyslipidemia (36 vs 29%), more smoking history (45 vs 22%), and less atrial fibrillation (16 vs 54%). ICAS patients had much higher re-occlusion rates (37 vs. 3%), higher rescue balloon angioplasty (9 vs. 1%), higher rescue intracranial stenting (38 vs. 3%), and longer puncture-to-reperfusion times (81 vs. 56 min). Despite these differences, outcomes, including percent with good final reperfusion (mTICI2b/3), symptomatic intracerebral hemorrhage, 90-day functional independence (mRS 0-2), and mortality, were surprisingly similar for both groups.

Perhaps one of the most important limitations of the study (and in clinical practice) is the difficulty in diagnosing ICAS-related LVOs. It is possible that LVOs were originally classified as ICAS-related based on several variables reported in the study resulting in selection bias, such as lack of atrial fibrillation. Indeed, the authors describe ICAS-related LVOs as being defined in many centers by residual stenosis >50% after EVT, re-occlusion during EVT, evidence of hypoperfusion in downstream territory, and ruling out other etiologies. Various imaging predictors have been described for their associations, including calcification on CT, clot burden on SWI, and patterns of infarcts, but none are definitive. Other limitations include possibly limited generalizability given the predominantly Asian ethnicity. The authors also discuss that collateral status was unavailable, and perhaps those with ICAS had better collaterals leading to favorable clinical outcomes despite longer revascularization times. Furthermore, long-term re-stenosis status and recurrent stroke data were not available.

Ultimately, this meta-analysis supports aggressively treating these patients with EVT, like LVOs from other etiologies, but warns that they may be technically more challenging. Re-occlusion is likely the major concern. Autopsy studies of post-EVT patients whose LVOs were ICAS-related showed evidence of fibrous cap disruption, intraplaque hemorrhage, and subintimal dissection, findings that presumably relate to re-occlusion risk. The authors discuss a recent study by Baracchini, et al. that showed rescue stenting may lead to improved outcomes compared to leaving arteries occluded. They surmise that rescue therapy with intra-arterial glycoprotein IIb/IIIa inhibitors, balloon angioplasty, and intracranial stenting may account for the similar outcomes in their meta-analysis despite the significantly higher re-occlusion rates and longer procedure times. They conclude that these approaches may be viable rescue treatment options. However, future studies must be completed to determine which is optimal. These studies will be challenging as ICAS-related LVOs are less common and each patient may have unique differences such as occlusion site, infarct size (bleeding risk of antiplatelet agents), and other variables.