Neuroimaging Features of Cytokine-related Diseases.

Cytokines are small secreted proteins that have specific effects on cellular interactions and are crucial for functioning of the immune system. Cytokines are involved in almost all diseases, but as microscopic chemical compounds they cannot be visualized at imaging for obvious reasons. Several imaging manifestations have been well recognized owing to the development of cytokine therapies such as those with bevacizumab (antibody against vascular endothelial growth factor) and chimeric antigen receptor (CAR) T cells and the establishment of new disease concepts such as interferonopathy and cytokine release syndrome. For example, immune effector cell-associated neurotoxicity is the second most common form of toxicity after CAR T-cell therapy toxicity, and imaging is recommended to evaluate the severity. The emergence of COVID-19, which causes a cytokine storm, has profoundly impacted neuroimaging. The central nervous system is one of the systems that is most susceptible to cytokine storms, which are induced by the positive feedback of inflammatory cytokines. Cytokine storms cause several neurologic complications, including acute infarction, acute leukoencephalopathy, and catastrophic hemorrhage, leading to devastating neurologic outcomes. Imaging can be used to detect these abnormalities and describe their severity, and it may help distinguish mimics such as metabolic encephalopathy and cerebrovascular disease. Familiarity with the neuroimaging abnormalities caused by cytokine storms is beneficial for diagnosing such diseases and subsequently planning and initiating early treatment strategies. The authors outline the neuroimaging features of cytokine-related diseases, focusing on cytokine storms, neuroinflammatory and neurodegenerative diseases, cytokine-related tumors, and cytokine-related therapies, and describe an approach to diagnosing cytokine-related disease processes and their differentials.