Fig 1.
A. Perilesional cortex (Cx) and white matter (WM) of an 8-year old male patient. B. Type A tuber (Cx and WM) in a 5-year old female patient with a tuber in the frontal lobe. C. Type B tuber (Cx and WM) located in the parietal lobe of an 8-year old boy (same as in Fig 1A). D. Type C tuber of a 2-year old male patient located in the frontal lobe. Scale bar in D = 100μm and applies also to A, B and C.
Fig 2.
mTORC1 activation, neuronal quantity and gliosis.
A.—D. mTOR activation was present in all cortical tuber types as well as in perituberal cortex (pS6-Ser235/236 staining). E. Gradient mTOR activation among the tuber types. F.—I. Loss in neuronal cell density could be observed in type B tubers (NeuN staining). J. Neurons were significantly depleted (p = 0.015). K.—N. Gliosis was present in all tuber types (GFAP staining). O. Increase of gliosis reached significance (p = 0.019). Scale bar in D, I, and N = 100μm and applies also to F, G, H, K, L, and M. CO = control; PT = perituberal cortex.
Table 1.
Quantification.
Fig 3.
Inflammatory markers and vessel structure.
A. Representative amount of T-cells lying in the white matter (WM) of control samples (CD3 staining). B. + C. T-cell content within type B and C tubers (CD3). D. Significant increase of CD3 positive cells in type B and C tubers compared to controls. E. Almost no microglial activation can be detected in autopsy cortex (Cr3/43 staining). F. + G. Representative WM of type B and C tubers showing an increase in microglial activation (Cr3/43). H. Quantification of the Cr3/43 positive content revealed a significant difference between controls and type B as well as C tubers. Scale bar in g = 100μm and applies also to a, b, c, e, f and g. CO = control; PT = perituberal cortex.
Fig 4.
White matter pathology in cortical tubers.
A. Normal appearing white matter content of the temporal lobe in a 17-years old autopsy case (MBP staining). B. + D. + E. Representative sections of WM within the 3 different tuber types (MBP). Scale bar in e = 100μm and applies also to a, b, and d. C. Significant reduction of myelin content. F. Equal distribution of oligodendroglial cells among all tuber types. CO = control; PT = perituberal cortex.
Fig 5.
A. Representative MRI of a patient with a histological type A tuber (histology is shown in Fig 1B) characterized by a hyperintense lesion parasaggital in the right frontal lobe (indicated by the arrow head) on T2 weighted and fluid-attenuated inversion recovery (FLAIR) and a hypointense signal in the same area on volumetric T1 images. B. MRI of a histological type B tuber (histology is shown in Fig 1C) with FCD-like features in the left postcentral/parietal region, showing as a hyperintense lesion on FLAIR image and a hypointense signal on 3DT1. FCD features are recognized by thickened cortex, blurring of gray and white matter junction and a transmantal sign. C. MRI of a histological type C tuber (histology is shown in Fig 1D) with a large calcification, characterized by deep hypointense signal with surrounding heterogenous hyperintense signal on T2 weighted and FLAIR images and a hypointense signal in the white matter on 3DT1. The above described FCD features are seen here as well.
Table 2.
Patients characteristics.