Myelin Pathology Beyond White Matter in Tuberous Sclerosis Complex (TSC) Cortical Tubers
Mühlebner A, Van Scheppingen J, De Neef A, Bongaarts A, Zimmer TS, Mills JD, Jansen FE, Spliet WG, Krsek P, Zamecnik J, Coras R, Blümcke I, Feucht M, Scholl T, Gruber VE, Hainfellner JA, Söylemezoǧlu F, Kotulska K, Lagae L, Jansen AC, Kwiatkowski DJ, Jozwiak S, Curatolo P, Aronica E (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 79
Pages Range: 1054-1064
Journal Issue: 10
DOI: 10.1093/jnen/nlaa090
Abstract
Tuberous sclerosis complex (TSC) is a monogenetic disease that arises due to mutations in either the TSC1 or TSC2 gene and affects multiple organ systems. One of the hallmark manifestations of TSC are cortical malformations referred to as cortical tubers. These tubers are frequently associated with treatment-resistant epilepsy. Some of these patients are candidates for epilepsy surgery. White matter abnormalities, such as loss of myelin and oligodendroglia, have been described in a small subset of resected tubers but mechanisms underlying this phenomenon are unclear. Herein, we analyzed a variety of neuropathologic and immunohistochemical features in gray and white matter areas of resected cortical tubers from 46 TSC patients using semi-automated quantitative image analysis. We observed divergent amounts of myelin basic protein as well as numbers of oligodendroglia in both gray and white matter when compared with matched controls. Analyses of clinical data indicated that reduced numbers of oligodendroglia were associated with lower numbers on the intelligence quotient scale and that lower amounts of myelin-associated oligodendrocyte basic protein were associated with the presence of autism-spectrum disorder. In conclusion, myelin pathology in cortical tubers extends beyond the white matter and may be linked to cognitive dysfunction in TSC patients.
Authors with CRIS profile
Involved external institutions
University of Amsterdam
Netherlands (NL)
Universitair Ziekenhuis Brussel
Belgium (BE)
Hacettepe University
Turkey (TR)
Medizinische Universität Wien
Austria (AT)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Children's Memorial Health Institute / Instytut "Pomnik - Centrum Zdrowia Dziecka"
Poland (PL)
Harvard University
United States (USA) (US)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Motol University Hospital / Fakultní nemocnice v Motole
Czech Republic (CZ)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
Netherlands (NL)
Universitair Ziekenhuis Brussel
Belgium (BE)
Hacettepe University
Turkey (TR)
Medizinische Universität Wien
Austria (AT)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Children's Memorial Health Institute / Instytut "Pomnik - Centrum Zdrowia Dziecka"
Poland (PL)
Harvard University
United States (USA) (US)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
Belgium (BE)
Motol University Hospital / Fakultní nemocnice v Motole
Czech Republic (CZ)
University Medical Centre Utrecht (UMC Utrecht)
Netherlands (NL)
How to cite
APA:
Mühlebner, A., Van Scheppingen, J., De Neef, A., Bongaarts, A., Zimmer, T.S., Mills, J.D.,... Aronica, E. (2020). Myelin Pathology Beyond White Matter in Tuberous Sclerosis Complex (TSC) Cortical Tubers. Journal of Neuropathology and Experimental Neurology, 79(10), 1054-1064. https://doi.org/10.1093/jnen/nlaa090
MLA:
Mühlebner, Angelika, et al. "Myelin Pathology Beyond White Matter in Tuberous Sclerosis Complex (TSC) Cortical Tubers." Journal of Neuropathology and Experimental Neurology 79.10 (2020): 1054-1064.
BibTeX: Download