Background: Acute Necrotizing Encephalopathy of Childhood (ANEC) is an illness characterized by rapidly progressive encephalopathy, typically associated with a precipitating viral illness such as influenza. It is diagnosed clinically and through neuroimaging showing symmetric multifocal lesions involving the deep grey matter, especially the thalamus. Morbidity and mortality in ANEC are high, so prompt recognition and treatment are key, but treatment protocols vary. We propose a management protocol based on a consensus approach and available evidence. Methods: A rapid literature review was conducted. Studies included were meta-analyses, case series, and expert consensus guidelines. Individual case reports were excluded. We identified interventions which have been used, and selected those with evidence or expert support for use in a protocol. The protocol was reviewed with stakeholders in pediatric neurology and PICU. Results: Reported treatments include high-dose steroids, IV immunoglobulins, tocilizumab, and plasmapheresis. The treatment with strongest evidence is high-dose steroids started within 24 hours of presentation. There is frequently reported use of IV immunoglobulins and plasmapheresis, and growing evidence to support use of tocilizumab (IL-6 blockade) within the first 48 hours. Conclusions: Overall, there is strong expert opinion that treatment should be initiated promptly. We present our centre’s protocol to expedite this treatment.