Literature reports on the natural history of cerebral cavernous malformations (CMs) are numerous, with considerable variability in lesion epidemiology, hemorrhage rates, and risk factors for hemorrhage. In this review, the authors performed a meta-analysis of 11 natural history studies. The overall male-to-female ratio was 1:1, and the mean age at presentation was 30.6 years. Overall, 37% of patients presented with seizures, 36% with hemorrhage, 23% with headaches, 22% with focal neurological deficits, and 10% were asymptomatic. Some patients had more than one symptom. Seizure presentation was most prevalent among supratentorial CMs, while focal neurological deficits were common in patients with infratentorial CMs. By location, CMs were in the cerebral hemispheres (66%), brainstem (18%), basal ganglia or thalamus (8%), cerebellum (6%), and other (2.5% [combined supra- and infratentorial, callosal or insular]). Overall, 19% of patients harbored multiple intracranial CMs, and 9% had radiographically apparent associated developmental venous anomalies. An overall annual hemorrhage rate of 2.4% per patient-year (range 1.6%–3.1%) was identified across 3 studies. Prior hemorrhage and female sex were risk factors for bleeding, while CM size and multiplicity did not affect hemorrhage rates. Although not impacting the hemorrhage rate itself, deep location was a risk factor for increased clinical aggressiveness.
ObjectCystic epithelial masses of the sellar and parasellar region may be difficult to differentiate on a clinical, imaging, or even histopathological basis. The authors review the developmental relationships and differentiating features of various epithelial lesions of the sellar region.MethodsThe authors performed a review of the literature to identify previous studies describing the etiological relationships and differentiating features of various cystic sellar lesions, including craniopharyngioma (CP), Rathke cleft cyst, xanthogranuloma, and dermoid and epidermoid cysts.ResultsThere is significant evidence in the literature to support a common ectodermal origin of selected sellar and suprasellar cystic lesions, which may account for the overlap of features and transitional states observed in some cases. Research obtained from animal studies and reports of transitional cystic epithelial masses or lesions crossing over from typical to more aggressive pathological subtypes have collectively provided a solid foundation for this theory. Histological features that signify transitional entities beyond simple benign Rathke cleft cysts include squamous metaplasia, stratified squamous epithelium, and ciliated or mucinous goblet cells in squamous-papillary CPs. Several studies have identified key clinical, imaging, and histopathological features that can be used in the differentiation of these lesions.ConclusionsThe pattern of embryological formation of the hypothalamic-pituitary axis plays a major role in its propensity for developing cystic epithelial lesions. Subsequent inflammatory, metaplastic, and neoplastic processes may promote further progression along the pathological continuum, ranging from benign epithelial cysts to aggressive neoplastic cystic CPs. Selected clinical, imaging, and histopathological features can be used collectively to help differentiate these lesions and assign a formal diagnosis, thus accurately guiding further treatment.
In acute stroke treated with Solitaire stent retriever thrombectomy, higher thrombus HU values are predictive of successful recanalization. Such information can be used in decision making when estimating recanalization success rate with different endovascular treatment approaches.
BLI offers a simple and rapid technique for assessing intracranial glioblastoma growth in rodent models noninvasively, which correlates well with MRI. The speed of the BLI technique can increase experimental throughput, allows for targeted histological analysis in animals showing the greatest treatment effects, and provides new insights into the kinetics of intracranial tumor growth in the setting of different treatments.
To understand further the role of the dynamic interplay between keratinocytes and stromal components in the regulation of the growth, differentiation, morphogenesis, and basement membrane assembly of human stratified squamous epithelium, we have generated novel, three-dimensional organotypic cultures in which skin keratinocytes were grown in the absence or presence of pre-existing basement membrane components and/or dermal fibroblasts. We found that keratinocytes cultured in the presence of pre-existing basement membrane components and dermal fibroblasts for 9 d showed rapid assembly of basement membrane, as seen by a nearly complete lamina densa, hemidesmosomes, and the polarized, linear distribution of laminin 5 and a6 integrin subunit. Basement membrane assembly was somewhat delayed in the absence of dermal fibroblasts, but did occur at discrete nucleation sites when pre-existing basement membrane components were present. No basement membrane developed in the absence of pre-existing basement membrane components, even in the presence of dermal fibroblasts. Bromodeoxyuridine incorporation studies showed that early keratinocyte growth was independent of mesenchymal support, but by 14 d, both fibroblasts and assembled basement membrane were required to sustain growth. Normalization of keratinocyte differentiation was independent of both dermal fibroblasts and structured basement membrane. These results indicated that epithelial and mesenchymal components play a coordinated role in the generation of structured basement membrane and in the regulation of normalized epithelial growth and tissue architecture in an in vitro model of human skin.
p53 is an essential tumor suppressor, whose activity is finely tuned by the posttranslational modifications. Previous research has reported that β-hydroxybutyrate (BHB) induces β-hydroxybutyrylation (Kbhb), which is a novel histone posttranslational modification. Here we report that p53 is modified by kbhb and that this modification occurs at lysines 120, 319, and 370 of p53. We demonstrate that the level of p53 kbhb is dramatically increased in cultured cells treated with BHB and in thymus tissues of fasted mice, and that CBP catalyze p53 kbhb. We show that p53 kbhb results in lower levels of p53 acetylation and reduced expression of the p53 downstream genes p21 and PUMA, as well as reduced cell growth arrest and apoptosis in cultured cells under p53-activating conditions. Similar results were observed in mouse thymus tissue under starvation conditions, which result in increased concentrations of serum BHB, and in response to genotoxic stress caused by γ-irradiation to activate p53. Our findings thus show that BHB-mediated p53 kbhb is a novel mechanism of p53 activity regulation, which may explain the link between ketone bodies and tumor, and which may provide promising therapeutic target for cancer treatment.
Background Integration of data from clinical trials and advancements in technology predict a change in selection for treatment of patients with cerebral aneurysm.
PED+coils may be a safe and effective treatment for aneurysms with high risk of rupture (or rerupture) and complex anatomy. Coiling in conjunction with PED placement provided a higher aneurysm occlusion rate and reduced the need for retreatment.
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