Abstract TP160: The Ring Finger Protein 213 Variant and Characteristics of Plaque, Vascular Remodeling and Hemodynamics in Patients With Intracranial Atherosclerotic Stroke: A High-Resolution Mri and Hemodynamic Study

Abstract

Background: Intracranial atherosclerotic stroke is prevalent in Asians. We hypothesized patients with the Ring Finger protein 213 ( RNF213 ) variant, a susceptibility locus for moyamoya disease in East Asians, have different neuroimaging characteristics in terms of vessel wall and hemodynamics. Methods: We analyzed consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant plaque on the distal internal carotid artery or proximal MCA on high-resolution MRI (HR-MRI). Patients with carotid/cardiac sources of embolism or angiographic features of moyamoya disease were excluded. HR-MRI features (e.g., outer vessel diameters and plaque characteristics) and fractional flow (as measured by adjusted signal intensity ratio on time-of-flight MRA) were compared between RNF213 p.Arg4810Lys variant carriers and non-carriers. Results: Of 144 patients included, 44 (29.9%) patients had the RNF213 variant. Clinical characteristics including age, gender, and vascular risk factors were not different between RNF213 variant carriers and non-carriers. However, outer vessel diameter was smaller in RNF213 variant carriers than in non-carriers (p<0.0001 for MCA of relevant stenosis, p<0.0001 for contralateral side, and p<0.001 for basilar artery). Other HR-MRI features including plaque morphology were not different. Fractional flow was diminished in patients with a smaller diameter of the intracranial arteries with the similar degree of stenosis. Conclusions: The RNF213 variant may be associated with vasculogenesis but not with atherogenesis. Patients with this variant had small intracranial arteries predisposing hemodynamic compromise in the presence of intracranial atherosclerosis. Beside anti-atherosclerotic strategies, further studies are warranted to develop a novel therapeutic strategies against RNF213 vasculopathy in Asians.