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NOVEL HISTOPATHOLOGICAL PATTERNS IN CORTICAL TUBERS IN TSC
last known ENGEL score 12 1 3 10 4 2 201 3 102
4 1 3 1 > 0.05
global cognitive impairment none 3 4 0 mild 152 moderate 0 2 3
severe 3 2 3 > 0.05
IQ 72.5 (45-102) 59 (48-107) 52 (34-68) > 0.05
Autism no 5 9 4
yes 2 3 4 > 0.05
3.00 10.00 (3.00- 7.00 (0.83- (1.00-
median age at surgery (range) 47.00) 22.00) 17.00) 0.002
4.00 2.21 median duration of ac- 8.00 (3.00- (0.80- (0.43-
tive epilepsy (range) 35.00) 13.00) 13.00) 0.004
only one group has applied whole slide scanning and compared fully automated and user-based approaches 27. In order to access a much broader spectrum of characteristics and obtain a more accurate diagnosis, we choose not to follow a ROI-based approach.
The limitation of choosing to assess all available tissue is the risk to miss subtle changes restricted to only part of the visible pathology. In light of this, our aim was not to specifically assess cellular features but primarily to find distinctive characteristics within the histology. Numerous studies exist to explore the pathogenetic mechanism behind the aberrant cells visible in TSC samples. However, these are often related to FCD Type IIB another pathology with similar histological features 28, 29, 30, 31.
Despite this limitation, it was possible to address several aspects that relate to pathophysiological mechanisms in tubers. In TSC patients mTORC1 activation as assessed by staining for various forms of phospho-S6 is expected due to the genetic nature of TSC. It provides a molecular explanation for the observed giant cells, although the molecular consequences of second-hit events are less well understood. In addition, pS6 has recently been detected immunohistochemically in the perituberal cortex 14 and mTORC1 activation is believed to begin in the fetal period 32, 33. However, we were not able to detect differences between tuber subgroups when compared to perituberal samples suggesting that also in our study the true margins of the lesion extent beyond the radiographically visible perituber 34.
Furthermore, our data suggests a gradient in the level of mTORC1 activation throughout all tuber types. Our identification of patterns would improve our under- standing of the molecular and functional events during tuber pathogenesis and eventu- ally help to find a better definition of perituberal tissue.
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