Acute necrotizing encephalopathy (ANE) or sometimes necrotizing encephalitis or infection-induced acute encephalopathy (IIAE) is a rare type of brain disease (

encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...

) that occurs following a viral infection. Most commonly, it develops secondary to infection with

influenza A ''Influenza A virus'' (''Alphainfluenzavirus influenzae'') or IAV is the only species of the genus ''Alphainfluenzavirus'' of the virus family '' Orthomyxoviridae''. It is a pathogen with strains that infect birds and some mammals, as well as c ...

, influenza B, and the human herpes virus 6. ANE can be familial or sporadic, but both forms are very similar to each other. Multiple subtypes, associated with specific genes have been found.

Symptoms and signs

Acute necrotizing encephalopathy typically appears in infancy or early childhood, although some people do not develop the condition until adolescence or adulthood. People with this condition usually show typical symptoms of an infection, such as fever, cough, congestion, vomiting, and diarrhea, for a few days. Following these flu-like symptoms, affected individuals develop neurological problems, such as seizures, hallucinations, difficulty coordinating movements (

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

), or abnormal muscle tone. Eventually, most affected individuals go into a coma, which usually lasts for a number of weeks. The condition is described as "acute" because the episodes of illness are time-limited. People with acute necrotizing encephalopathy develop areas of damages (

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...

s) in certain regions of the brain. As the condition progresses, these brain regions develop swelling (

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

), bleeding (

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

), and then tissue death (

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

). The progressive brain damage and tissue loss results in encephalopathy.

Genetics

ANE can be familial or sporadic, but both forms are very similar to each other. Most familial cases are caused by genetic changes in the RANBP2 gene, and are known as infection-induced acute encephalopathy 3 (IIAE3) or acute necrotizing encephalopathy type 1 (ANE1). In addition there is acute infection-induced (herpes-specific) encephalopathy-1 (IIAE1) associated with a homozygous UNC93B1 gene; and herpes-specific IIAE2 associated with the TLR3 gene; as well as IIAE4, associated with the CPT2 gene; herpes-specific IIAE5 associated with the TRAF3 gene; herpes-specific IIAE6 associated with the TICAM1 gene; herpes-specific IIAE7 associated with the

IRF3 Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. Function IRF3 is a member of the interferon regulatory transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. IR ...

gene; herpes-specific IIAE8 associated with the TBK1 gene; IIAE9 associated with the NUP214 gene; herpes-specific IIAE10 associated with the SNORA31 gene; and herpes-specific IIAE11 associated with the DBR1 gene.

Diagnosis

Treatment

Randomized clinical trials have not been published, and optimal treatment regimes for the condition are not known. Suggested treatments may be

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s and

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

regulators such as

TNF inhibitor Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

Prognosis

Approximately one-third of individuals with acute necrotizing encephalopathy do not survive their illness and subsequent neurological decline. Of those who do survive, about half have permanent brain damage due to tissue necrosis, resulting in impairments in walking, speech, and other basic functions. Over time, many of these skills may be regained, but the loss of brain tissue is permanent. Other individuals who survive their illness appear to recover completely. It is estimated that half of individuals with acute necrotizing encephalopathy are susceptible to recurrent episodes and will have another infection that results in neurological decline; some people may have numerous episodes throughout their lives. Neurological function worsens following each episode as more brain tissue is damaged.

History

The first case in the medical literature was described in 1955 by Belgian neurologist Ludo van Bogaert. A sharp increase in cases during the 2024-2025 United States influenza season was flagged by

ProMED Program for Monitoring Emerging Diseases (also known as ProMED-mail, abbreviated ProMED) is among the largest publicly available emerging diseases and outbreak reporting systems in the world. The purpose of ProMED is to promote communication amon ...

on February 6, 2025. https://promedmail.org/promed-post/?place=8722003,106

References

External links

Radiopedia - Acute necrotizing encephalopathy

ANE International
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