Early High-Dose Methylprednisolone Therapy Is Associated with Better Outcomes in Children with Acute Necrotizing Encephalopathy

Abstract

Background: The neurologic outcomes of acute necrotizing encephalopathy (ANE) are very poor, with a mortality rate of up to 40% and fewer than 10% of patients surviving without neurologic deficits. Steroid and immunoglobulin treatments have been the most commonly used options for ANE, but their therapeutic efficacy is still controversial. Method: We retrospectively reviewed the medical records of 26 children diagnosed with ANE. We also divided these patients into two groups: 21 patients with brainstem involvement and 8 patients without brainstem involvement. Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) and intravenous immunoglobulin (2 g/kg for 2–5 days) were administered to treat ANE. Results: The overall mortality rate was 42.3%, and patients who did not survive had significantly higher initial lactate and serum ferritin levels, as well as higher rates of inotropic agent use with brainstem involvement. There were no significant differences in the outcomes of pulse steroid therapy or pulse steroid plus immunoglobulin between survivors and non-survivors. When analyzing the time between symptom onset and usage of pulse steroid therapy, pulse steroid therapy used within 24 h after the onset of ANE resulted in significantly better outcomes (p = 0.039). In patients with brainstem involvement, the outcome was not correlated with pulse steroid therapy, early pulse steroid therapy, or pulse steroid therapy combined with immunoglobulin. All patients without brainstem involvement received “early pulse methylprednisolone” therapy, and 87.5% (7/8) of these patients had a good neurologic outcome. Conclusion: Pulse steroid therapy (methylprednisolone at 30 mg/kg/day for 3 days) administered within 24 h after the onset of ANE may be correlated with a good prognosis. Further studies are needed to establish a consensus guideline for this fulminant disease.

Case Report: Acute Necrotizing Encephalopathy Following COVID-19 Vaccine

“…Hence, with these elements, we suggest that our patient's treatment blunted the immune response to the vaccine and explains the negative serologies. Rapid treatment may have influenced the positive outcome in our patient's situation, as has been retrospectively shown in children with ANE (25).…”

Acute Necrotizing Encephalitis as an Early Manifestation of COVID-19

“…While ANE is certainly an uncommon sequela of COVID-19, the exact risk is difficult to estimate, in part because of underdiagnosis and underreporting. One recent literature review identified 23 published adult cases of COVID-19-related ANE, most of which occurred in patients without prior neurologic comorbidities [3]. Future populationbased studies would be instructive in determining the actual incidence of ANE in COVID-19.…”

“…Acute necrotizing encephalopathy (ANE) is a para-infectious autoimmune condition that typically affects children suffering from influenza, but has also been reported in adults and related to other viral infections [2,3]. ANE occurs within days to weeks of viral symptoms and fever and is often characterized by rapid progression to coma in the absence of cerebrospinal fluid (CSF) pleocytosis.…”

“…ANE is associated with high mortality, in part due to delayed diagnosis given its rarity and often delayed imaging in clinically unstable patients. Early immunosuppression with intravenous (IV) corticosteroids, IVIg, and/or plasmapheresis appears to improve outcomes, but the optimal treatment paradigm remains unclear [3,4]. ANE has been associated with SARS-CoV-2 infection in adults [5][6][7][8][9][10][11] and children [12,13].…”

Case report: Acute necrotizing encephalopathy: a report of a favorable outcome and systematic meta-analysis of outcomes with different immunosuppressive therapies

“…The most frequently reported immunosuppressive therapy is high dose intravenous (IV) steroids [methylprednisolone, (MP) at least 30/mg/kg/day for at least 3 days] ( 8 , 10–14 ). Additionally, case reports and case series report the use of intravenous immune globulin (IVIG) ( 10 , 15 , 16 ), plasma exchange (PLEX) ( 10 , 16–19 ), and biologics such as tocilizumab (an IL-6 inhibitor) ( 8 , 11 , 19 , 20 ). Supportive care and symptomatic management in an intensive care unit (ICU) is necessary in most cases for depressed mental status, seizure control, blood pressure support, multisystem organ failure management which often requires intubation ( 3 , 8 , 16 , 19 ).…”