Neuroinflammation in Children With Infantile Spasms: A Prospective Study Before and After Treatment With Acthar Gel (Repository Corticotropin Injection).

Autor: Chugani HT; Department of Neurology, 5894NYU School of Medicine and the NYU Langone Comprehensive Epilepsy Center, New York, NY, USA., Kumar A; Departments of Pediatrics and Radiology, Children's Hospital of Michigan, 198459Wayne State University School of Medicine, Detroit, MI, USA.
Jazyk: angličtina
Zdroj: Journal of child neurology [J Child Neurol] 2020 Oct; Vol. 35 (12), pp. 808-812. Date of Electronic Publication: 2020 Jun 23.
DOI: 10.1177/0883073820932710
Abstrakt: The selective effectiveness of adrenocorticotropic hormone (ACTH) in treating infantile spasms suggests an underlying neuroinflammation. Because neuroinflammation is mediated by activated microglia, which express translocator protein (TSPO), we imaged neuroinflammation in children with infantile spasms using positron emission tomography (PET) with 11 C-PK11195 (PK), which selectively binds to TSPO. Children were studied prospectively before and following treatment with Acthar Gel (repository corticotropin injection). We hypothesized that PK-PET would show neuroinflammation (increased PET uptake) in cortical and/or subcortical structures before treatment, and that this inflammation will be abolished/reduced following Acthar Gel treatment. Eight children with infantile spasms (5 males; mean age 1.8±1.1, range 0.9-4.1 years) were recruited. After clinical and video electroencephalograph (EEG) evaluation and dynamic PK-PET scan, children underwent treatment with Acthar Gel over 4 weeks, followed by repeat clinical evaluation/video-EEG 2 weeks after initiation of treatment and repeat PK-PET 2 weeks after treatment completion. Visual and quantitative analysis of PK-PET scans were performed. We calculated regional binding potential (measure of receptor-ligand binding) using a reference tissue model. Focal areas of increased PK-binding were found in the pretreatment PK-PET in 5 children. Following treatment, these increases were either reduced or normalized and were associated with cessation (n=4) or significant reduction (n=1) of spasms and complete disappearance of hypsarrhythmia. One child showed increased binding potential in basal ganglia and thalamus, despite normalization of cortical binding potential; however, these increases were likely associated with death-related causes. This study suggests Acthar Gel-responsive neuroinflammatory changes in children with infantile spasms, supporting a potential role of neuroinflammation in the pathogenesis of infantile spasms.
Databáze: MEDLINE