Acute necrotising encephalopathy is more severe when associated with influenza

Background and objective: Acute Necrotising Encephalopathy (ANE) is a rare but potentially life-threatening condition associated with viral infections A familial and recurrent form (ANE1) has been identified by mutations in the nuclear pore Ran Binding Protein (RANBP2) We report the morbidity and mortality when associated with Influenza infection Method(s): We performed a review of paediatric ANE cases from 1999 to 2019 evaluating the clinical, biochemical, microbiological and neuroimaging appearances as well as outcomes Result(s): The cohort comprised 6 children (2 boys), age ranging from 8 months to 3 years 9 months ( 2y n=5), of which 4 had a confirmed genetic diagnosis and 2 were RANBP2 negative There were 13 episodes of encephalopathy, with recurrences in 3 cases (2 ANE1) 10 of these episodes had infectious aetiology identified: coronavirus n=2, parainfluenza n=1, adenovirus n=2, H influenzae n=1, influenza (H1N1 n=3, H3N2 n=1) Clinical features of fever and encephalopathy were consistent (100%), and seizures and sixth nerve palsies prominent (50% each) CSF revealed absent pleocytosis, normal-elevated protein and negative virology Symmetric involvement of the thalami bilaterally was present in all cases, and all ANE1 cases were associated with haemorrhage and external capsule/claustrum involvement (100% specific and sensitive) The outcome following influenza infection was striking, death n=1, vegetative n=2, 4 limb motor and movement disorder n=1 2 of these cases had previous episodes of encephalopathy with noninfluenza infection and did have recovery, albeit with moderate to severe disability All 3 cases were never immunised against Influenza infection and suffered grave outcomes Conclusion(s): Influenza infection in ANE has the poorest outcome therefore vaccination should be a mandatory consideration for the known cases of ANE