Given the high prevalence of m.3243A>G mutation and common carrier status of several pathogenic variants in POLG gene (p. A467T, p. W748S and p. G848S) in populations of European descent [29], clinicians should prioritise mitochondrial disease as a main differential diagnosis to atypical, evolving posterior circulation stroke, recurrent ‘encephalitis/encephalopathy’ with negative infective screen, auto-antibodies and ‘atypical/recurrent’ posterior reversible encephalopathy syndrome (PRES). This evidence concerns the gene POLG and Posterior Leukoencephalopathy Syndrome.