The interplay of infection and genetics in acute necrotizing encephalopathy

Acute necrotizing encephalopathy (ANE) presents with fulminant encephalopathy and characteristic brain lesions following viral infection. The rarity and unpredictability of the disorder have significantly impaired its study. Growing recognition of ANE and the discovery of causative missense mutations in the nuclear pore gene RANBP2 give promising steps toward unraveling this disease. This review summarizes recent advances of clinical and scientific understanding of ANE.

Inflammatory factors participate in the pathogenesis of ANE, but the lack of difference between influenza and noninfluenza ANE focuses attention on the abnormal host response as causative. Early treatment with steroids provides the best outcome for patients who do not have brainstem lesions. Missense mutations in RANBP2 cause the majority of familial and recurrent ANE cases, but other single-gene causes of ANE are possible for familial, recurrent, and sporadic cases.

Early recognition and systematic evaluation of ANE are necessary. Modeling ANE as a genetic disorder may provide the most immediate gains in the understanding and treatment of ANE and related disorders.