To test this hypothesis, we evaluated the potential correlation between the severity of MTHFR mutation (considering both MTHFR polymorphism and homocysteinemia levels), the degree of endothelial dysfunction (indirectly measured as L-Arg/ADMA levels), and the IAS phenotype (by echocardiographic assessment) in patients diagnosed with Embolic Stroke of Undetemined Source (ESUS).If confirmed, this hypothesis might also help to legitimize L-Arg/ADMA as a marker of endothelial dysfunction. This evidence concerns the gene MTHFR and hyperhomocysteinemia.