Clinical and genetic risk factors and long-term outcomes of MRI vessel wall enhancement in moyamoya disease

Background: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). However, the genetic background and risk factors for VWE in MMD have not been investigated. Therefore, this study assessed potential risk factors for VWE in MMD.Methods: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE group and non-VWE group based on the presence or absence of VWE on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors were compared using KaplanMeier survival and Cox regression.. STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines were followed for reporting our cohort study.Results: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (P = 0.014) and a higher incidence of ischemia and hemorrhage (P =0.002) than did the non-VWE group. Multiple logistics regression shows risk factors for VWE included the ring finger protein 213 (RNF213) pR4810K variant (OR: 2.01 [95% confidence interval (CI), 1.08 - 3.76]; P = 0.028), hyperhomocysteinemia (HHcy; OR: 5.08 [95% CI, 2.34 - 11.05], P < 0.001), and smoking history (OR, 3.49 [95% CI, 1.08-11.31], P = 0.037). During the follow-up of 63.9 13.2 months (medium 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and RNF213 pR4810K variant were risk factors for follow-up stroke. Conclusion: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE; both are likely to induce the VWE phenomenon by affecting vascular endothelial function or causing vascular endothelial damage. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by grants from the National Natural Science Foundation of China (grant numbers 82171280 and 82172021). Science and Technology Commission Project (2019-JCJQ-ZD-195-00). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Ethics Committee of the Fifth Medical Center of the PLA General Hospital approved this study (reference number: 20150622). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Owing to some sensitive information present in the study database, it is not freely available in the public domain currently. However, specific proposals for possible collaborations are welcome. Researchers interested in further information and collaboration are invited to contact the corresponding author Duan Lian via email [duanlian307@sina.com]