Glioblastoma in a Patient With MELAS Syndrome: A Case Report

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) syndrome is a multi-systemic genetic disorder characterized by mitochondrial dysfunction, often presenting with diverse clinical phenotypes. We report a rare case of glioblastoma (GBM) in a 60-year-old female whose MELAS manifestations were primarily metabolic and neuro-sensory. Her clinical course began at age 40 with diabetes mellitus, bilateral sensorineural hearing loss, and left ophthalmoplegia. She was diagnosed with MELAS syndrome by molecular genetic testing at age 56 following her son's diagnosis. Despite the absence of previous stroke-like episodes, she presented with an acute 2-day history of headache, vomiting and altered mental status. Brain MRI revealed a mass lesion, and subsequent gross total resection was performed. Histopathological and molecular analysis confirmed a GBM, IDH-wildtype (CNS WHO grade 4). Despite surgical resection, the patient failed to recover neurologically, remaining in a stuporous state with eye opening but inability to follow commands. She subsequently received the Stupp protocol; however, massive local recurrence with increased relative cerebral blood volume was observed within one month of treatment initiation, indicating rapid and aggressive tumor progression. This case underscores that in MELAS patients, primary brain malignancies can arise independently of typical stroke-like episodes. In addition, the unusually aggressive clinical course and rapid recurrence despite standard Stupp protocol therapy raise the possibility that altered mitochondrial metabolism may influence tumor behavior or treatment response in certain patients.