Genetic and environmental risk factors of acute infection-triggered encephalopathy

Abstract

Acute encephalopathy is a constellation of syndromes in which immune response, metabolism and neuronal excitation are affected in a variable fashion. Most of the syndromes are complex disorders, caused or aggravated by multiple, genetic and environmental risk factors. Environmental factors include pathogenic microorganisms of the antecedent infection such as influenza virus, human herpesvirus-6 and enterohemorrhagic Escherichia coli, and drugs such as non-steroidal anti-inflammatory drugs, valproate and theophylline. Genetic factors include mutations such as rare variants of the SCN1A and RANBP2 genes, and polymorphisms such as thermolabile CPT2 variants and HLA genotypes. By altering immune response, metabolism or neuronal excitation, these factors complicate the pathologic process. On the other hand, some of them could provide promising targets to prevent or treat acute encephalopathy.

Keywords: acute encephalopathy; drug; immune response; infection; metabolism; neuronal excitation; susceptibility gene.

FIGURE 1

Association between pathogens of antecedent infection and encephalopathy syndromes. A bold line indicates high incidence, based on epidemiologic data in Japan (Hoshino et al., 2012; Kasai et al., 2020). ANE, acute necrotizing encephalopathy; AESD, acute encephalopathy with biphasic seizures and late reduced diffusion; FIRES, febrile infection-related epilepsy syndrome; HHV, human herpesvirus; HSES, hemorrhagic shock and encephalopathy syndrome; MERS, clinically mild encephalitis/encephalopathy with reversible splenial lesion; RSV, respiratory syncytial virus.

FIGURE 2

Genetic and environmental risk factors and major pathologic processes of severe acute encephalopathy. HLA, human leukocyte antigen; NSAIDs, non-steroidal anti-inflammatory drugs.