Introduction: Pathophysiology of stroke-like episodes (SLEs) in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes) is presumed to involve mitochondrial energy failure causing neuronal injury and microangiopathy. L-arginine (L-Arg) during acute SLEs may be associated with a reduction in severity of SLEs.

Case description: A 10-year-old boy with mtDNA A3243G tRNA Leu mutation presented with acute encephalopathy, right focal seizures, motor apraxia and expressive aphasia. MRI showed left temporal lobe gyriform cortical diffusion restriction with mass effect.   He was treated with oral L-Arg  500 mg/kg/d and within 24 hours showed rapid improvement of symptoms. He suffered repeated emesis of his L-Arg with recrudescent encephalopathy, apraxia and aphasia. He was started on iv L-Arg 500mg/kg/d for 24 hours and then 200mg/kg/d for 48 hours and symptoms quickly reversed again to baseline. L-Arg was then slowly tapered to 1 g tid po maintenance.  At 13 years, he presented with an URTI and emesis.  Six days later he suffered acute intermittent frontal headaches with transient diplopia and vomiting. MRI showed new symmetric lesions of the putamen and lesion of the right pons.  He was again treated with high dose iv L-Arg. Within 24 hours he had complete resolution of symptoms. MRI repeated 3 days later showed resolution of the pontine lesion.

Discussion: L-Arg is converted to nitric oxide, which is important in vasodilation and is a precursor for creatine and may improve TCA cycle anaplerosis. The consistent reversal of SLEs following high dose L-Arg in this case supports a therapeutic response.