INTRODUCTION: Acute necrotizing encephalopathy (ANE) is characterized by fulminant encephalopathy with bilateral thalamic lesions associated with a recent viral infection that often progresses to seizures, coma and death. There has been an association with Ran Binding Protein 2 (RANBP2) missense mutations and ANE, leading to familial clusters of ANE. Despite research into this disease, it remains a rare diagnosis. We present the case of a 7-year-old male with a history of RANBP2 mutation who presented in status epilepticus following an influenza A infection and despite treatment proceeded to tonsillar herniation and brain death.
DESCRIPTION: A 7-year-old male presented to care following several days of upper respiratory symptoms and fevers. He developed generalized tonic-clonic seizures and required intubation for persistent encephalopathy. His neurologic exam was notable for hypertonia and hyperreflexia with a non-localizing response to pain. A head computed tomography (CT) scan was initially unremarkable. He was found to be influenza A positive. Over the next 12 hours, he became less responsive with a suddenly unresponsive pupillary exam. His EEG recording showed no evidence of seizures but was consistent with severe cerebral slowing that progressed to electrocerebral silence. A repeat head CT scan demonstrated swelling of the thalamus bilaterally. Discussion with his family revealed that he had RANBP2 mutation and his sister had survived ANE with static encephalopathy. Despite maximal medical and surgical therapies he continued to exhibit an absence of brainstem reflexes. Treatment with steroids and intravenous immunoglobulin were attempted without improvement. Magnetic resonance imaging (MRI) demonstrated edema of the brainstem, thalami, and hippocampus, tonsillar herniation, and absence of flow-related enhancement in the Circle of Willis. He did not regain cerebral function and was declared brain dead 3 days after admission.
DISCUSSION: ANE is a rare but potentially fatal viral associated disease that can have a familial association, particularly with RANBP2 mutations. There is no evidence supported treatment regimen. Our experience suggests that intensive care providers and neurologists should be familiar with ANE as a source for seizures that can rapidly progress to death.