Outcomes of Endovascular Therapy in Young Patients with Acute Basilar Artery Occlusion: A Substudy of BASILAR Registry Study

Our study provided evidence of a better prognosis in young patients with acute BAO. Besides, baseline NIHSS, baseline pc-ASPECTS, and sex were independently associated with clinical outcomes in young EVT cohorts. Furthermore, we revealed young patients with BAO due to dissection.

The appropriate age definition of “young” patients with stroke is unclear. In the literature, age ranges of 18–40 [20], 18–49 [10], or 18–55 [21] years have been given for young patients with stroke. Fifty-five years is the cutoff age in some studies [21‐23] with appropriate sample sizes, taking into consideration the fact that individuals younger than 55 years of age usually remain healthy because of improving medical conditions. In the BASILAR registry, the occurrence of young patients (aged 18–55 years) with stroke was 23.5% of the whole EVT cohort. The frequency of young patients (aged < 50 years) with stroke was approximately 19% in the BASICS registry study [8] and 11.3% in the BASICS trial [6] of all acute BAO. Our study found that young patients with stroke had a good arterial collateral network (PC-CS > 5 scores, 60.52% vs. 46.35%, p = 0.002). A possible explanation was that cardiovascular risk factors may impede angiogenesis during the pruning of collaterals [14]. Thus, chronic exposure to cardiovascular risk factors such as hypertension, diabetes mellitus, and smoking could impair endothelial function and stiffen the vessels’ myogenic tone leading to a decline in artery diameter [24, 25]. Two subgroup analyses of MR CLEAN also noted that young patients with stroke had higher collateral circulation grade scores (grade 3, 27.60% vs. 18.50%, p < 0.001 [10]; median age, grade 1 vs. grade 3 = 72 years vs. 67 years, p < 0.001 [14]). Besides, 5.26% of young patients showed vessel dissection, which is an etiological factor for stroke due to BAO. Dissections involving the basilar artery have been reported much less frequently. The Helsinki Young patients with stroke Registry showed that 2 of 426 patients (4.69%) had basilar artery dissection and 68 of 532 patients (12.78%) had internal carotid dissection [26]. Chang et al. [27] also observed that 6.9% of young patients had vessel dissection in patients with posterior circulation ischemic stroke. Indeed, we found that the occurrence of vessel dissection was 11.40% in patients aged less than 50 years with acute BAO.

Young patients were associated with better clinical outcomes, which was consistent with existing literature [10, 11, 28, 29]. For example, 40.78% (62/152) of young patients with stroke achieved favorable outcomes at 90 days, resulting in a difference of 11.43% (95% CI 2.65–20.22) compared with old patients. Besides, mortality within 90 days was less frequent in young patients (37.50% vs. 48.99%, p = 0.013) with an absolute difference of 11.49% (95% CI 2.62–20.36). At 1-year follow up, the Kaplan–Meier survival plot (Fig. 3) also indicated that young adults had a better prognosis. In a real-world multicenter experience, 66.20% of young patients (aged < 50 years) who underwent EVT because of large artery occlusion achieved favorable outcomes and 4.70% of the patients died [11]. For these patients, the rate of favorable clinical outcome (mRS 0–2) at 3 months was higher (61.00% vs. 38.80%) and mortality was lower (6.80% vs. 31.90%) than in old patients according to the MR CLEAN Registry [10]. One possible explanation could be that young patients with stroke are in general healthier individuals with more compensatory capabilities and less comorbidity. Another explanation could be that young patients have a lower prevalence of cardiovascular risk factors and thus they a higher probability of achieving complete rehabilitation than old patients. Supporting this idea, young patients were found to have good artery collateral circulation, which has been associated with a favorable outcome and low mortality.

Our findings also reveal associations between admission NIHSS, pc-ASPECTS, and recanalization and favorable outcomes at 90 days, which is further supported by previous studies [30, 31]. Interestingly, we found sex as an independent predictor of mortality within 90 days for young patients. Indeed, young women have a lower probability of mortality within 90 days (19.35% vs. 42.15%, p = 0.02) and less cardiovascular risk (hypertension (38.71% vs. 64.46%, p = 0.009) and dyslipidemia (25.81% vs. 46.28%, p = 0.04) compared with men (eTable 5 in the supplementary material). This is in contradiction with the findings of previous studies that showed sex was independently associated with clinical prognosis. Eriksson et al. revealed that the association between sex and clinical outcome was not significant for patients with ischemic stroke [32]. Chalos et al. [33] also demonstrated that sex could not predict mortality within 90 days in patients who underwent EVT. Among patients with BAO, Tan et al. [34] indicated that the functional outcomes were comparable between men and women. One cause of the discrepancy between ours and the aforementioned studies may be the included population. While these studies aim to analyze the differences in sex based on the whole population, our study analyzes young patients with stroke only. Estrogen is considered a protective factor against ischemic stroke in young women because of its neuroprotective and anti-inflammatory properties [35]. Consistently, the risk of stroke more rapidly increases in postmenopausal women, in whom estrogen levels are lower. Up to 35.80% of women with ischemic stroke, a staggering number of 100,000, are aged 60–69 years, while 19.67% are aged 50–59 years [36]. Meanwhile, good collateral circulation is associated with low mortality. Pooled data from 1764 participants in the seven randomized controlled trials on EVT within the HERMES collaboration showed that women have higher collateral grades (grade 3, 46% vs. 35%; p < 0.001) than men [33]. MR CLEAN subgroup analysis reported that women have good collateral circulation (grade 3, 53% vs. 47%) [14]. Our findings also showed that young female cohorts have high collateral grades (64.52% vs. 59.50%), but the difference between men and women was insignificant. In addition, lower rates of bridge intravenous thrombolysis (19.07% vs. 39.40%), hypertension (59.21% vs. 76.20%), and diabetes (19.07% vs. 28.8%), and shorter onset to puncture time (330 vs. 359.60 mins) were found in young patient in our study compared with a multicenter cohort study [34]. The findings of Guenego et al. supported our results as sex was a predictor of mortality in patients with BAO treated with EVT [37]. However, the mortality within 1 year is comparable between men and women (eTable 5 in the supplementary material). The Kaplan–Meier curve of young patients with stroke (eFig. 2 in the supplementary material) revealed that mortality increases more rapidly at 9 months in women than in men. Stroke unit care may improve neurological recovery [38]. However, female patients were less likely to be admitted directly to the stroke unit, hence missing the opportunity to achieve functional independence compared with male patients [32]. In stroke management, women are less likely to receive therapeutic statins or anticoagulation [39], which may increase the risk of stroke. We hypothesize that women may have high rates of stroke recurrence. In fact, we found a higher prevalence of atrial fibrillation (22.58% vs. 5.79%, p = 0.01) and cardioembolism (25.81% vs. 12.40%, p = 0.001), which are considered predictors of stroke recurrence, in women compared with men. Besides, a meta-analysis showed that 3.1% of patients had stroke recurrence at 90 days and 11.1% at 1 year [40]. Regrettably, information on stroke recurrence was not available from the BASILAR Registry and thus we were unable to identify the stroke recurrence in women at 30 days and 1 year after EVT.

One of the strengths of this study is its elucidation of the characteristics of BAO in young adults. In addition, the effect of EVT also was investigated in young and old patients with stroke due to acute BAO. Nevertheless, our study has some limitations. As a retrospective national registry, it was a non-randomized study, which confers an inherent risk of bias and an inability to determine causality. We could only determine the etiology of stroke in young patients with BAO. The difference between young and old patients was not entirely identified. The unequal number of young and old cohorts found in our study was due to stroke being a common disease of old age. Considering the age strata difference, multivariable analyses were used to adjust the unequal clinical outcomes. Additionally, the sample size of the young patients was moderate. Further large prospective studies are warranted to further investigate this relationship.