MRI findings reveal three different types of tubers in patients with tuberous sclerosis complex

Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types along a spectrum of severity, using magnetic resonance imaging (MRI) characteristics in 35 patients with TSC and history of epilepsy, and to investigate the relationship between tuber types and genetics, as well as clinical manifestations. Three types of tubers were identified based on the MRI signal intensity of their subcortical white matter component. (1) Tubers Type A are isointense on volumetric T1 images and subtly hyperintense on T2 weighted and fluid-attenuated inversion recovery (FLAIR); (2) Type B are hypointense on volumetric T1 images and homogeneously hyperintense on T2 weighted and FLAIR; (3) Type C are hypointense on volumetric T1 images, hyperintense on T2 weighted, and heterogeneous on FLAIR characterized by a hypointense central region surrounded by a hyperintense rim. Based on the dominant tuber type present, three distinct patient groups were also identified: Patients with Type A tuber dominance have a milder phenotype. Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance.