Reversible Cerebral Vasoconstriction Syndrome With Ischemic Stroke Underlying Ring Finger Protein 213 Vasculopathy

Dear Editor,Ring finger protein 213 (RNF213) gene has been identified as a major susceptibility gene for moyamoya disease.[1][2][3] Recent studies have demonstrated that RNF213 polymorphism may contribute not only to intracranial arteriopathy, but also shows extracranial vessel involvement.3 Although the precise mechanism by which RNF213 variants lead to vascular stenosis remains unclear, several hypotheses including endothelial dysfunction have been proposed.[3][4][5] Reversible cerebral vasoconstriction syndrome (RCVS), which is considered as distinct etiology, is also an emerging topic of interest as it is another disease entity showing multifocal narrowing of intracranial vessels.6,7 Here, we report a rare case of extracranial vasculopathy associated with RNF213 polymorphism, presenting with clinical features of RCVS.A 46-year-old woman with no underlying medical conditions visited emergency department with headache, accompanying visual disturbance and subjective paraparesis.She visited emergency department 3 days prior due to chest pain, which led to elective coronary angiography which showed no significant findings leading to consideration for variant angina.Her headache was pressing bilaterally-especially at left hemisphere-with symptom severity fluctuating and lasting for hours, generally presenting with VAS (visual analogue scale) score 7. Neither photophobia nor phonophobia was present, nausea and vomiting were also absent.Blood pressure, heart rate, and respiratory rate were within normal range.Computed tomography (CT) angiography demonstrated multiple moderate to severe stenosis involving anterior and posterior circulation (Fig. 1A) raising suspicion for RCVS.After admission, IV nimodipine was started.Further evaluation with magnetic resonance (MR) imaging including vessel wall imaging revealed diffusion restriction in left posterior cerebral artery territory (Fig. 1B) along with evidence of negative remodeling in multiple sites of intracranial vessels including middle cerebral artery without wall enhancement (Fig. 1C and D).Subsequent aortogram showed occlusion of celiac artery and severe stenosis of superior mesenteric artery (SMA) (Fig. 1E).Given the presence of multifocal stenosis in both intracranial and extracranial arteries, genetic testing for RNF213 polymorphism was performed which revealed heterozygote variant at p.Arg4810Lys.Antiplatelet agent was initiated to treat acute infarction and multiple extracranial artery stenosis.Over the following days, patient's headache was improved.Follow-up MR angiography after 8 days of admission showed improved stenosis (Fig. 1F), confirming diagnosis of RCVS.She was discharged shortly thereafter with remaining weak paresthesia on right lower extremity.Subsequent MR angiography performed a year later showed similar findings which presented multiple mild intracranial stenosis (Fig. 1G).Extracranial arteriopathy in RNF213 polymorphism is typically reported in coronary artery, renal artery, celiac trunk and SMA. 3 This aligns with this case, which demonstrated oc-Hong