Ivy Sign Predicts Ischemic Stroke Recurrence in Adult Moyamoya Patients without Revascularization Surgery

Abstract

Background: Although there is a standard guideline for performing revascularization surgery in patients with Moyamoya diseases (MMD), more objective and easily obtainable predictors are still needed. Objectives: In this study, we aimed to evaluate the relationship between an ipsilateral ivy sign and ischemic stroke recurrence in adult MMD patients without revascularization surgery. Methods: We included consecutive MMD patients without revascularization surgery between 2006 and 2014. The ivy sign was defined as a linear or focal high-signal intensity on fluid-attenuated inversion recovery images, and the burdens of ivy sign were rated in each hemisphere. The ischemic stroke recurrence was defined as a new clinical event that accompanied a new brain lesion on magnetic resonance imaging. Results: Overall, 84 patients with 154 hemispheres were analyzed. We found recurrent ischemic stroke in 9 (6%) hemispheres within 3 years. In multivariate analysis, an ipsilateral ivy sign remained an independent predictor of 3-year ischemic recurrence (adjusted hazard ratio [aHR] 10.15, 95% CI 2.10–49.14, p = 0.004). An initial presentation as infarction was also significant (aHR 7.15, 95% CI 1.36–36.78, p = 0.019). The burdens of ivy sign showed a dose-response tendency with the 3-year ischemic recurrence rate (p < 0.001). When comparing the ischemic recurrence rate among 4 groups with and without ivy sign and perfusion defect, the “Ivy sign (+) Perfusion defect (+) group” showed a significantly higher risk in both observed (p = 0.005) and estimated (p = 0.003) 3-year ischemic recurrence than did the other group. Additionally, the “Ivy sign (+) Perfusion defect (–) group” showed a higher recurrence rate than did the “Ivy sign (–) Perfusion defect (+) group”. Conclusions: The ivy sign is associated with ischemic recurrence in adult MMD patients in a dose-response manner. It would be helpful for selecting high-risk patients who need revascularization surgery.

What and why: the current situation and future prospects of “ivy sign” in moyamoya disease

“…65 However, there are limited data addressing the question of prognosis between MMD patients with and without ivy sign under conservative treatment, although the "Ivy sign (+) group" showed a higher ischemic recurrence rate than did the "Ivy sign (-) group" in Nam et al's study. 31 (4) In previous studies, perfusion "abnormalities" are reported to correspond to ivy sign dominant regions. While perfusion parameters such as CVR, CBF, CBV, and OEF may reflect an abnormality, clinical relevance between ivy sign and perfusion "abnormalities" is not yet clear.…”

“…23 These were confirmed by subsequent studies. 20,24,31 By using positron emission tomography, Vuignie et al also found that ivy sign was significantly correlated with the increase OEF. 23 Consistently, the improvement of CVR after direct or indirect bypass surgery brought about a decrease in ivy sign.…”

“…23 Furthermore, in the conservative treatment group, ivy sign is an independent predictor of ipsilateral 3-year ischemic recurrence. 31 Interestingly, Ishii et al and Horie et al observed that, instead of decreasing, ivy sign increased after operations. 25,28 These de novo ivy signs were observed in more than 50% hemispheres on affected sides, and were significantly related to postoperative hyperperfusion.…”

“…16 However, results from Jin et al, Jung et al and Nam et al found no significant correlation between ivy sign and the stenosis sites/severity of intracranial arteries. 21,27,31 A positive correlation between the appearance of ivy sign and the development of leptomeningeal collaterals was discovered by Kawashima et al, 17 while Kronenburg et al found no correlation via DSA and arterial spin labeling (ASL) MRI. 33 Besides, Ishii et al found the postoperative reduction of ivy sign was not significantly correlated with good collateral circulation from bypass surgery.…”

“… 23 Furthermore, in the conservative treatment group, ivy sign is an independent predictor of ipsilateral 3-year ischemic recurrence. 31 Interestingly, Ishii et al . and Horie et al .…”