Brain cytotoxic edema is a neuroradiological sign secondary to variegate diseases ranging from migraine to fulminant Listeria rhombencephalitis. The tempestive identification of its underlying cause is vital for an effective treatment as any delay may be fatal. However, the lack of distinctive imaging biomarkers and the paucity of reports pose a significant challenge in its diagnosis and frequently lead to a misdiagnosis particularly with the more common acute ischemic stroke. Importantly, due to its rarity, mesencephalon midline cytotoxic lesion is likely to remain an underdiagnosed clinical phenomenon, especially if follow up MRI is not performed. Here we report a case of a central, midline, symmetric midbrain cytotoxic edema in a haemodialysis patient with diverse chronic progressive severe cardiovascular risk factors and a newly diagnosed atrial fibrillation. We expand the spectrum of neuroradiological hallmarks associated to terminal renal failure and report a full moon-like mesencephalon midline transient restricted diffusion as a reliable imaging biomarker for the prompt and accurate diagnosis of midbrain cytotoxic edema with the enormous potential of rapidly identifying and effectively treating its causative factors and timely reverse the associated symptomatic.