To describe a case of nonconvulsive status epilepticus (NCSE) in a patient with MELAS syndrome occurring in the absence of new stroke-like lesions, highlighting the role of mitochondrial dysfunction and metabolic instability in epileptogenesis.

A 22-year-old woman with molecularly confirmed MELAS (m.3243A>G, 30% heteroplasmy) and homozygous MTHFRC677T mutation presented with focal seizures progressing to NCSE after intermittent discontinuation of L-arginine supplementation. Continuous EEG showed 2–3 Hz rhythmic spike– and polyspike–wave discharges in the right temporo-parieto-occipital region with anterior propagation, lasting 12–15 seconds, resolving after intravenous midazolam. Brain MRI demonstrated chronic occipital and lingual gyrus gliosis without new diffusion- or FLAIR-restricted lesions. Antiseizure therapy was optimized with brivaracetam and clobazam, and metabolic therapy with L-arginine and citrulline was reinstated.

The patient achieved full clinical and electrographic recovery without new neurological deficits. The episode was attributed to metabolic decompensation secondary to nitric oxide deficiency following L-arginine withdrawal.