BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes,
leading to constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway. Cortical tubers represent
typical lesions of the central nervous system (CNS) in TSC. The pattern of cortical layering disruption observed in brain
tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal
cell types recognized in tubers.
METHODS: In the present study, we aimed to characterize dysmorphic neurons (DNs) and
giant cells (GCs) of cortical tubers using neocortical layer-specific markers (NeuN, SMI32, Tbr1, Satb2, Cux2, ER81, and RORbeta)
and to compare the features with the histo-morphologically similar focal cortical dysplasia (FCD) type IIb. We studied a cohort
of nine surgically resected cortical tubers, five FCD type IIb, and four control samples using immunohistochemistry and in
RESULTS: Cortical tuber displayed a prominent cell loss in all cortical layers. Moreover, we observed
altered proportions of layer-specific markers within the dysplastic region. DNs, in both tubers and FCD type IIb, were found
positive for different cortical layer markers, regardless of their laminar location, and their immunophenotype resembles that
of cortical projection neurons.
CONCLUSIONS: These findings demonstrate that, similar to FCD type IIb, cortical layering
is markedly disturbed in cortical tubers of TSC patients. Distribution of these disturbances is comparable in all tubers and
suggests a dysmaturation affecting early and late migratory patterns, with a more severe impairment of the late stage of maturation.