Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation

Stroke-like lesions (SLL) are common radiological findings in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (SLE; MELAS) harboring the m.3243A > G MTTL1 mutation. Imaging patterns in the m.3243A > G mutation carriers with encephalopathies lacking SLE have not been systematically examined to date. The aim of this study was to analyze brain imaging findings in encephalopathies associated with the m.3243A > G mutation irrespective of the presence or absence of SLE. Brain MRI and cranial CT scans from 11 m.3243A > G mutation carriers with encephalopathies were analyzed by two neuroradiologists in consensus. We evaluated stroke-like lesions (SLL), deep grey matter (DGM) changes on T1- and T2-weighted MR images, calcification on CT, brain atrophy, and white matter (WM) changes. SLL were present in all patients showing the full MELAS phenotype with SLE (4/11). Seven patients did not show SLE. DGM changes with T1 hyperintensity and T2 hypointensity were a distinctive finding in most patients (7/11) and present in the majority of m.3243A > G mutation carriers lacking SLE (5/7). DGM changes were also seen in half of our MELAS patients with SLL (2/4), though less pronounced. Brain atrophy was a prominent finding in general and accentuated in the cerebellum. In contrast, WM changes were rather mild and more prevalent and pronounced in MELAS. Our data stress that the distinction between MELAS with SLE and m.3243A > G mutation carriers lacking SLE is rather artificial. In clinical practice, mitochondrial disorders associated with the m.3243A > G mutation should be taken into consideration in encephalopathies with DGM changes, even when SLE and SLL are lacking.