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

Abstract

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.

MRI Characterization and Longitudinal Study of Focal Cerebellar Lesions in a Young Tuberous Sclerosis Cohort

“…A relationship between a certain subtype of cortical tubers "type C" and a more severe phenotype has been suggested, with the "type C" tubers corresponding to the previously described cystlike tuber type. 21 Clinically, these patients had difficult-to-control and more frequent seizures as well as lower intelligence quotient scores, 21 and they also had a larger cortical tuber burden, a higher percentage of the TSC2 gene mutation, and a higher occurrence of SGAs. 21 There was, however, no significant difference detected in the percentage of cerebellar lesions among the 3 cortical tuber groups, again raising questions of whether cerebellar lesions and SGAs are related and whether either are indicative of a more severe disease subset.…”

“…21 Clinically, these patients had difficult-to-control and more frequent seizures as well as lower intelligence quotient scores, 21 and they also had a larger cortical tuber burden, a higher percentage of the TSC2 gene mutation, and a higher occurrence of SGAs. 21 There was, however, no significant difference detected in the percentage of cerebellar lesions among the 3 cortical tuber groups, again raising questions of whether cerebellar lesions and SGAs are related and whether either are indicative of a more severe disease subset. Cerebellar tubers are not reported to occur in the absence of cortical tubers, and patients with cerebral and cerebellar tubers have significantly more global cortical lesions than patients without cerebellar tubers.…”

DTI of tuber and perituberal tissue can predict epileptogenicity in tuberous sclerosis complex

“…Cystic degeneration of tubers also causes increased ADC, which is consistent with the notion that tubers with cystic degeneration correlate with epileptogenicity. 6 It is possible that the functional isolation of the tuberal regions by cystic white matter may promote epileptogenicity. In future studies, it would be beneficial to directly analyze the relationship of imaging/DTI findings to electrocorticographic findings and histopathologic features.…”

Topographical Distribution of Epileptogenic Tubers in Patients With Tuberous Sclerosis Complex

“…Type C tubers have characteristics related to a more cystic tuber, namely hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and heterogeneous enhancement patterns on fluid-attenuated inversion recovery (hypointense central region surrounded by a hyperintense rim). Type C tubers have more severe clinical consequences, 27 including higher frequency of subependymal giant cell tumors, a higher likelihood for autism spectrum disorder, and a higher frequency of epileptic seizures. 28 The distribution of tubers across these different phenotypes is shown in Table 2.…”

“…Each tuber was characterized according to radiographic phenotype as outlined by Gallagher et al 27 In general, epileptogenic type A tubers occurred more frequently in the medial frontal cortex, bilaterally ( …”