This Expert Series will focus on MELAS, the difference between an actual stroke and stroke-like episodes, nitric oxide, and the use of citrulline. MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) is one of the most frequent maternally inherited mitochondrial disorders with an estimated prevalence of 60/100,000. There is growing evidence that nitric oxide (NO) deficiency occurs in MELAS and results in impaired blood perfusion that can contribute to several complications, including stroke-like episodes. Dr. Scaglia will discuss the results that led to the implementation of the current phase 1 dose-finding and safety clinical trial that is to determine the maximum tolerated dose (MTD) of citrulline in adults with MELAS.