Vascular involvement in the pathogenesis of mitochondrial encephalomyopathies.

OBJECTIVE

The aim of this study was to perform perfusion CT imaging in the acute phase of myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), to assess whether these patients had cerebral perfusion abnormalities. Furthermore, the pathology of muscle vessel was evaluated, to explore the role of vasculopathy and ischemic events in the pathogenesis of mitochondrial encephalomyopathies.

METHODS

Computed tomography perfusion (CTP) imaging was applied to the evaluation of brain perfusion during the symptomatic period of mitochondrial encephalomyopathies. Mitochondria structures in the blood vessels wall within muscle fibers were observed by light and electron microscopy analyses.

RESULTS

Neuroimaging studies demonstrated uni- and bilateral lesions predominantly in the occipital and temporal-parietal lobes. Compared with the healthy control subjects, significant decreases in cerebral blood flow and cerebral blood volume were noted in affected brain areas of individuals with MELAS. In particular, mean transit time and the time to peak were prolonged both in lesion and non-lesion brain areas. Muscle pathology showed large granular deposits on vessel wall as demonstrated by succinic acid dehydrogenase staining. Electron microscopy of blood vessels revealed swelling of cristae and a striking increase in the number of mitochondria in the smooth muscle and endothelial cells.

CONCLUSIONS

Insufficient cerebral perfusion or vascular reserve and secondary metabolic dysfunction may represent an important feature of the pathogenesis of the stroke-like episodes in MELAS.