Acute necrotizing encephalopathy (ANE) is a rare but distinctive type of acute 
encephalopathy with global distribution. Occurrence of ANE is usually preceded 
by a virus-associated febrile illness and ensued by rapid deterioration. 
However, the causal relationship between viral infections and ANE and the exact 
pathogenesis of ANE remain unclear; both environmental and host factors might be 
involved. Most cases of ANE are sporadic and nonrecurrent, namely, isolated or 
sporadic ANE; however, few cases are recurrent and with familial episodes. The 
recurrent and familial forms of ANE were found to be incompletely 
autosomal-dominant. Further the missense mutations in the gene encoding the 
nuclear pore protein Ran Binding Protein 2 (RANBP2) were identified. Although 
the clinical course and the prognosis of ANE are diverse, the hallmark of 
neuroradiologic manifestation of ANE is multifocal symmetric brain lesions which 
are demonstrated by computed tomography (CT) or magnetic resonance imaging 
(MRI). The treatment of ANE is still under investigation. We summarize the 
up-to-date knowledge on ANE, with emphasis on prompt diagnosis and better 
treatment of this rare but fatal disease.