Fatal outcome in a case of recurrent acute necrotizing encephalopathy with RANBP2 gene mutation: importance and difficulty of an early MRI pattern recognition

Case Report: Acute necrotizing encephalopathy (ANE) is a rare disease with seizures and deterioration of consciousness triggered by a common febrile illness. It was first described in East Asia as monophasic disorder in children, predominantly in association with influenza infection. Mutations in RANBP2 gene were published 2009 in patients with a recurrent course or positive family history (ANE1). The typical MRI findings for ANE include symmetrical involvement of thalami, putamen, brainstem, and cerebral and cerebellar white matter.

We report a 7-year old boy with febrile seizures during an influenza B infection followed by reduced vigilance. MRI showed symmetric lesions in thalamus and brainstem. Cerebrospinal fluid investigations revealed elevated protein and lactate concentrations without pleocytosis. Because of suspected ANE high dose steroid therapy was started. Nevertheless the patient developed a rapidly progressive supra- and infratentorial brain edema and finally died of brainstem herniation. The boy had previously been hospitalized at 5 months, 2 and 4 years of age with milder manifestations and complete remission. During the first episode the MRI was normal. At 2 years symmetrical lesions of amygdalae, hippocampi, external capsule, and thalami as well as involvement of the corpus callosum and the right occipital cortex were present. At 4 years the MRI showed bilateral changes of thalami and a cortical edema of the right hemisphere. Because of this history we suspected ANE1 and a heterozygous missense mutation in RANBP2 could be detected.

Diagnosing ANE based on the MRI pattern allows an early treatment with steroids. Patients with ANE1 may experience episodes with milder symptoms and their MRI can be normal or exhibit unspecific changes. Affection of the limbic system and the external capsule indicates a higher recurrence risk. In our case, an earlier diagnosis would have been an indication for a protective influenza vaccination.