Font Size: 

Background:MELAS syndrome is characterized by recurrent stroke-like episodes that constitute a major source of morbidity and mortality. The latter are presumed to result from both direct neuronal energy failure and functional angiopathy. It has been suggested that L-arginine reduces frequency and severity of stroke-like episodes, but the underlying mechanism is unclear. Methods:We performed a case control study in 3 siblings with MELAS syndrome to evaluate baseline cerebrovascular reactivity (CVR) and perfusion using BOLD-fMRI. We then conducted a prospective clinical trial pilot study to assess the response of these parameters to single dose and 6-week steady-state oral L-arginine. Results:MELAS subjects had lower serum arginine levels, and demonstrated decreased CVR and increased cerebral perfusion at baseline relative to controls. The latter abnormalities correlated with percentage of mutant mtDNA in blood. On regional analysis, mean CVR was reduced to a greater degree in frontal compared to occipital cortex. Following L-arginine therapy, MELAS subjects showed an increase in CVR in frontal cortex and a corresponding decrease in occipital cortex; CVR globally was unchanged. There was a dramatic reduction in hyperperfusion following steady state L-arginine in one MELAS subject. Discussion:Interictal vascular reactivity and cerebral perfusion are abnormal in MELAS syndrome in accordance with disease severity. L-arginine therapy does not improve overall CVR interictally; however, it seems to selectively improve CVR in the regions that are most impaired at the expense of less abnormal regions. It may also decrease hyperperfusion, possibly by improving energy metabolism or normalizing vascular tone.

MELAS; cerebrovascular reactivity; L-arginine