Distinct DNA Methylation Patterns of Subependymal Giant Cell Astrocytomas in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC.

MicroRNA-34a activation in tuberous sclerosis complex during early brain development may lead to impaired corticogenesis.

Aims: Tuberous sclerosis complex (TSC) is a genetic disorder associated with dysregulation of the mechanistic target of rapamycin complex 1 (mTORC1) signalling pathway. Neurodevelopmental disorders, frequently present in TSC, are linked to cortical tubers in the brain. We previously reported microRNA-34a (miR-34a) among the most upregulated miRs in tubers.

Myelin Pathology Beyond White Matter in Tuberous Sclerosis Complex (TSC) Cortical Tubers.

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.

Effects of valproic acid on histone deacetylase inhibition in vitro and in glioblastoma patient samples.

Background: The antiepileptic drug valproic acid (VPA) inhibits histone deacetylase in glioblastoma cells in vitro, which influences several oncogenic pathways and decreases glioma cell proliferation. The clinical relevance of these observations remains unclear, as VPA does not seem to affect glioblastoma patient survival. In this study, we analyzed whether the in vitro effects of VPA treatment on histone acetylation are also observed in tumor tissues of glioblastoma patients.

Dysregulation of the MMP/TIMP Proteolytic System in Subependymal Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex: Modulation of MMP by MicroRNA-320d In Vitro.

Tuberous sclerosis complex (TSC), a rare genetic disorder caused by a mutation in the TSC1 or TSC2 gene, is characterized by the growth of hamartomas in several organs. This includes the growth of low-grade brain tumors, known as subependymal giant cell astrocytomas (SEGA). Previous studies have shown differential expression of genes related to the extracellular matrix in SEGA.

The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas.

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the CNS, TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to impaired circulation of CSF resulting in hydrocephalus and raised intracranial pressure in patients with TSC.

Changes in vascular density in resected tissue of 97 patients with mild malformation of cortical development, focal cortical dysplasia or TSC-related cortical tubers.

Recent studies suggested a possible association between malformations of cortical development and microvascular density. In this study we aimed to further elucidate the relation between microvascular density and cortical developmental abnormalities in a cohort of 97 patients with epilepsy and histologically proven mild malformation of cortical development (mMCD), focal cortical dysplasia (FCD) or tuberous sclerosis complex (TSC). Surgical tissue samples were analyzed with quantitative measures of vessel density, T-cell response, microglial activation and myelin content.

Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates.

Introduction: The subventricular zone (SVZ) in the brain is associated with gliomagenesis and resistance to treatment in glioblastoma. In this study, we investigate the prognostic role and biological characteristics of subventricular zone (SVZ) involvement in glioblastoma.

Methods: We analyzed T1-weighted, gadolinium-enhanced MR images of a retrospective cohort of 647 primary glioblastoma patients diagnosed between 2005-2013, and performed a multivariable Cox regression analysis to adjust the prognostic effect of SVZ involvement for clinical patient- and tumor-related factors.

Precise detection of low-level somatic mutation in resected epilepsy brain tissue.

Low-level somatic mutations have been shown to be the major genetic etiology of intractable epilepsy. The extents thereof, however, have yet to be systematically and accurately explored in a large cohort of resected epilepsy brain tissues. Moreover, clinically useful and precise analysis tools for detecting low-level somatic mutations from unmatched formalin-fixed paraffin-embedded (FFPE) brain samples, the most clinically relevant samples, are still lacking.

Histological Differences of the Vascular Wall Between Sites With High and Low Prevalence of Intracranial Aneurysm.

Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle of Willis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.

Cognitive functioning after epilepsy surgery in children with mild malformation of cortical development and focal cortical dysplasia.

Mild malformation of cortical development (mMCD) and focal cortical dysplasia (FCD) subtypes combined are by far the most common histological diagnoses in children who undergo surgery as treatment for refractory epilepsy. In patients with refractory epilepsy, a substantial burden of disease is due to cognitive impairment. We studied intelligence quotient (IQ) or developmental quotient (DQ) values and their change after epilepsy surgery in a consecutive series of 42 children (median age at surgery: 4.

Long-term seizure outcome after epilepsy surgery in patients with mild malformation of cortical development and focal cortical dysplasia.

Focal cortical dysplasia (FCD) and mild malformation of cortical development (mMCD) are frequent histopathologic diagnoses in patients who undergo surgery for refractory epilepsy. Literature concerning surgical outcome in patients with mMCD, as well as its contrast with FCD, has been scarce. We studied 88 patients with a histopathologic diagnosis of isolated FCD (n = 57) or mMCD (n = 31), revised according to the latest International League Against Epilepsy (ILAE) guidelines, who underwent resective or disconnective surgery.

Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma.

Epilepsy at presentation is an independent favorable prognostic factor in glioblastoma (GBM). In this study, we analyze the oncologic signaling pathways that associate with epilepsy in human GBMs, and that can underlie this prognostic effect. Following ethical approval and patient consent, fresh frozen GBM tissue was obtained from 76 patient surgeries.

MicroRNA519d and microRNA4758 can identify gangliogliomas from dysembryoplastic neuroepithelial tumours and astrocytomas.

Glioneuronal tumours, including gangliogliomas and dysembryoplastic neuroepithelial tumours, represent the most common low-grade epilepsy-associated brain tumours and are a well-recognized cause of intractable focal epilepsy in children and young adults. Classification is predominantly based on histological features, which is difficult due to the broad histological spectrum of these tumours. The aim of the present study was to find molecular markers that can be used to identify entities within the histopathology spectrum of glioneuronal tumours.

Data on vessel wall thickness measurements of intracranial arteries derived from human circle of Willis specimens.

In this article, we report data on vessel wall thickness parameters derived from different arterial segments of the circle of Willis and its primary branches in patients with and without cerebrovascular disease. Also data on inter-rater reliability and agreement of the derived vessel wall parameters are reported. For further interpretation and discussion please refer to the research article "ex vivo vessel wall thickness measurements of the human circle of Willis using 7T MRI" (Harteveld et al.

Ex vivo vessel wall thickness measurements of the human circle of Willis using 7T MRI.

Background And Aims: MRI can detect intracranial vessel wall thickening before any luminal stenosis is present. Apart from representing a vessel wall lesion, wall thickening could also reflect normal (age-related) variations in vessel wall thickness present throughout the intracranial arterial vasculature. The aim of this study was to perform vessel wall thickness measurements of the major intracranial arteries in ex vivo circle of Willis (CoW) specimens using 7T MRI, to obtain more detailed information about wall thickness variations of the intracranial arteries.

Prognostic relevance of tumor-infiltrating lymphocytes and immune checkpoints in pediatric medulloblastoma.

Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity.

Proteomic profiling of the spinal cord in ALS: decreased ATP5D levels suggest synaptic dysfunction in ALS pathogenesis.

Background: We aimed to gain new insights into the pathogenesis of sporadic ALS (sALS) through a comprehensive proteomic analysis.

Methods: Protein profiles of the anterior and posterior horn in post-mortem spinal cord samples of 10 ALS patients and 10 controls were analysed using 2D-differential gel electrophoresis. The identified protein spots with statistically significant level changes and a spot ratio >2.

7 tesla T2*-weighted MRI as a tool to improve detection of focal cortical dysplasia.

Focal cortical dysplasia is one of the most common underlying pathologies in patients who undergo surgery for refractory epilepsy. Absence of a MRI-visible lesion necessitates additional diagnostic tests and is a predictor of poor surgical outcome. We describe a series of six patients with refractory epilepsy due to histopathologically-confirmed focal cortical dysplasia, for whom pre-surgical 7 tesla T2*-weighted MRI was acquired.

Functional aspects of early brain development are preserved in tuberous sclerosis complex (TSC) epileptogenic lesions.

Tuberous sclerosis complex (TSC) is a rare multi-system genetic disease characterized by several neurological disorders, the most common of which is the refractory epilepsy caused by highly epileptogenic cortical lesions. Previous studies suggest an alteration of GABAergic and glutamatergic transmission in TSC brain indicating an unbalance of excitation/inhibition that can explain, at least in part, the high incidence of epilepsy in these patients. Here we investigate whether TSC cortical tissues could retain GABAA and AMPA receptors at early stages of human brain development thus contributing to the generation and recurrence of seizures.

Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex.

Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions.

Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis omplex (TSC): evidence from layer-specific marker expression.

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.