Pathogenesis and Management of Acute Necrotizing Encephalopathy

ABSTRACT

Introduction

During the COVID−19 pandemic, many cases of acute necrotizing encephalopathy (ANE) secondary to COVID−19 have been reported. ANE is characterized by a rapid onset, a fulminant course, and low morbidity and fatality rates. Therefore, clinicians need to be vigilant for such disorders, especially during the influenza virus and COVID−19 epidemics.

Areas covered

The authors summarize the most recent studies on the clinical spectrum and treatment essentials of ANE to provide references for prompt diagnosis and improved treatment of this rare but fatal disease.

Expert opinion

ANE is a type of necrotizing lesion of the brain parenchyma. There are two major types of reported cases. One is isolated and sporadic ANE, which is primarily caused by viral infections, particularly influenza and HHV−6 virus. The other type is familial recurrent ANE, which is caused by RANBP2 gene mutations. ANE patients have rapid progression and a very poor prognosis, with acute brain dysfunction occurring within days of viral infection and requiring admission to the intensive care unit. Clinicians still need to investigate and find solutions for the problems of early detection and treatment of ANE.

KEYWORDS:

• acute necrotizing encephalopathy
• accessory infection
• COVID-19
• influenza
• cytokine storm

Article highlights

• ANE is primarily associated with viral infection-induced cytokine storms and genetic susceptibilities, such as RANBP2 gene mutation, the thermolabile phenotype of carnitine palmitoyltransferase II (CPTII) polymorphism, human leukocyte antigen (HLA) genotype and other genetic variables.

• ANE is characterized by rapid progression of acute encephalopathy with no specific symptoms or neurological signs.

• The imaging findings revealed multifocal and symmetrical brain lesions, most of which involved the bilateral thalamus, basal ganglia, brainstem tegmental cortex, and cerebellar white matter.

• The main treatment methods include immunotherapy, anti-IL6 therapeutics, mild hypothermia, CRRT and adjuvant supportive therapy.

• ANE patients have a very poor prognosis and progress quickly, with acute brain dysfunction occurring within days of viral infection and requiring intensive care admission.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Joint Medical Research Project of Chongqing Science & Technology and Health Commission (2020FYYX081) the High-Level Medical Reserved Personnel Training Project of Chongqing, and the Natural Science Foundation of Yuzhong Direct, Chongqing (20190129).