Potential inflammatory mechanisms of the ketogenic diet against febrile infection-related epilepsy syndrome

Abstract

Febrile infection-related epilepsy syndrome (FIRES) is a rare epilepsy syndrome with unclear pathogenesis, characterized by fever-induced, super-refractory status epilepticus and high mortality. Studies have shown that ketogenic diet (KD) is effective in controlling convulsions in FIRES, but its mechanisms are unclear. This paper intends to summarize the mechanisms by which KD may exert effects against FIRES. Clinical studies have shown that patients with FIRES have elevated levels of various inflammatory factors such as interleukin (IL)-6, IL-8, IL-10, and so on. KD may exert anti-FIRES effects through several potential inflammatory pathways, including nuclear factor -κB (NF-κB) and NLR family pyrin domain containing 3 (NLRP3). Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) network suggested that KD may play an anti-inflammatory role through several pathways such as cellular senescence and neutrophil extracellular trap formation. These mechanisms need to be further investigated.

Keywords: Febrile infection-related epilepsy syndrome; Inflammation; Ketogenic diet; Mechanisms.

Fig. 1

Potential inflammatory pathways for KD against FIRES. Clinical studies on FIRES have shown that the levels of cytokines and Toll-like receptors are elevated. Laboratory studies on epilepsy have shown that the levels of inflammasomes are also elevated. Meanwhile, KD may exert its anti-inflammatory effects through multiple pathways. AIM2 Absent in melanoma 2. ASC Apoptosis-associated speck-like protein with a caspase-recruitment domain. CCL C–C motif ligand. EP Epilepsy. FIRES Febrile infection-related epilepsy syndrome. GPR109A G protein-coupled receptor 109A. HDACs Histone deacetylases. HMGB1 High Mobility Group Protein 1. IFN-γ Interferon gamma. IL Interleukin. KD Ketogeic diet. MCP Monocyte chemotactic protein. MIP Macrophage inflammatory protein. NF-κB Nuclear factor-κB. NLRP NLR family pyrin domain containing. S100A8/A9 S100 calcium-binding protein A8/A9. sTNFr2 Soluble tumor necrosis factor receptor 2. TLR Toll-like receptor. TNF-α Tumor necrosis factor alpha

Fig. 2

KEGG network for possible mechanisms of KD against FIRES. KD may play its anti-inflammatory role through pathways, either directly or indirectly. AMPK Adenosine monophosphate-activated protein kinase. MAPK Microtubule-associated protein kinase