Font Size: 

Background:Stroke-like episodes constitute a major source of morbidity and mortality in MELAS syndrome. The pathophysiology of these episodes is incompletely understood, but is presumed to involve both direct neuronal injury and functional angiopathy as a result of mitochondrial energy failure. We performed a case control study using Blood Oxygen Level Dependent (BOLD) fMRI to evaluate baseline cerebral blood flow (CBF) and arterial cerebrovascular reactivity(CVR). Methods:We enrolled 3 siblings with MELAS syndrome (A3243G tRNA leu) with varying percentages of mutant mtDNA and 4 healthy age and gender-matched controls. CBF was calculated using arterial spin labeling methodology. For CVR studies, subjects were fitted with an air-tight sequential gas delivery mask with gas delivery controlled using the RepirAct sequencer. Subjects were given a series of four CO2 challenges where PaCO2 was raised 10 mmHg above their baseline with PaO2 maintained at 100 mmHg. Results:MELAS subjects demonstrated increased CBF and decreased CVR compared to controls, and the degree of abnormality correlated with disease severity and percentage of mutant mtDNA in blood. On regional analysis, mean CVR was reduced to a greater degree in the frontal compared to the occipital cortices. Discussion:Patients with MELAS syndrome have impaired CVR and cerebral hyperperfusion in between stroke-like episodes, lending credence to a vascular and/or hemodynamic contribution to the latter. CVR and CBF may serve as prognostic markers to stratify risk for stroke-like episodes.

MELAS; cerebrovascular reactivity; stroke-like episodes