Histological and neuroimaging comparison of SMART syndrome versus focal neuronal gigantism

Two of the rarest radiation-induced adverse effects are focal neuro-nal gigantism (FNG) and SMART syndrome (stroke-like migraine attacks after radiation therapy). Both conditions develop years, and sometimes decades, after receipt of therapeutic radiation to the brain. To date, there are only 3 previously reported cases of FNG, all of which describe cortical thick-ening, enlarged hypertrophic neurons, and neuronal cytological changes. No de-tailed studies exist of histological features of SMART or the comparison between FNG and SMART. In this study, we contrast histo-logical and neuroimaging features of 3 FNG vs. 4 SMART cases, the latter diagnosed by a neuroradiologist, neurooncologist, and/ or neurosurgeon. We confirm the cortical thickening, dyslamination, neuronal cyto-megaly, and gliosis in FNG vs. cortical archi-tectural preservation and normal neuronal cytology in SMART, although both showed gliosis, scattered neurons with cytoplas-mic accumulation of tau and neurofibrillary protein and variable co-existence of other radiation-induced lesions. Both conditions lacked significant inflammation or consis-tent small vessel hyalinization throughout the entire resection specimen. The absence of pathognomonic histologic alterations in SMART cases suggests underlying vascular dysregulation. Despite differing histology, some overlap may exist in neuroimaging features. Molecular assessment conducted in 2 cases of FNG was negative for significant alterations including in the MAPK pathway.

Automated summary

This study compares the histological and neuroimaging features of focal neuronal gigantism (FNG) and SMART syndrome (stroke-like migraine attacks after radiation therapy). The results show that FNG is characterized by cortical thickening, dyslamination, neuronal cyto-megaly, and gliosis, while SMART preserves normal cortical architecture and neuronal cytology. Both conditions show gliosis, cytoplasmic accumulation of tau and neurofibrillary protein in scattered neurons, but it is more pronounced in FNG. The study also found no significant inflammation or consistent small vessel hyalinization in both conditions.