In patients with refractory traumatic intracranial hypertension, decompressive craniectomy resulted in lower mortality but higher proportions of vegetative state and severe neurological impairment compared to ongoing medical management. Level of evidence: 1B (CEBM, Individual RCT of good quality)
Glioblastoma (GBM) is an aggressive primary tumor, causing thousands of deaths worldwide every year. The mean survival of patients with GBM remains below 20 months despite current available therapies. GBM cells' interactions with their stromal counterparts are crucial for tumor development. Astrocytes are glial cells that comprise~50% of all brain cells and are therefore likely to establish direct contact with GBM cells. As other tumor cell types can hijack fibroblasts or immune cells to facilitate tumor growth, GBM cells can actually activate astrocytes, namely, the tumor associated astrocytes (TAAs), to promote GBM invasion in the healthy tissue. TAAs have thus been shown to be involved in GBM cells growth and limited response to radiation or chemotherapy (i.e., Temozolomide). Nevertheless, even though the interest in the cancer research community is increasing, the role of TAAs during GBM development is still overlooked.Yet, obtaining an in-depth understanding of the mechanisms by which TAAs influence GBM progression might lead to the development of new therapeutic strategies. This article therefore reports the different levels of GBM progression at which TAAs have been recently described to be involved in, including tumor cells' proliferation/invasion and resistance to therapies, especially through the activity of extracellular vesicles. K E Y W O R D S brain, glioblastoma, stromal cells, tumor associated astrocytes, tumor microenvironment
Glioblastoma (GBM) is one of the most aggressive solid tumors for which treatment options and biomarkers are limited. Small extracellular vesicles (sEVs) produced by both GBM and stromal cells are central in the inter-cellular communication that is taking place in the tumor bulk. As tumor sEVs are accessible in biofluids, recent reports have suggested that sEVs contain valuable biomarkers for GBM patient diagnosis and follow-up. The aim of the current study was to describe the protein content of sEVs produced by different GBM cell lines and patient-derived stem cells. Our results reveal that the content of the sEVs mirrors the phenotypic signature of the respective GBM cells, leading to the description of potential informative sEV-associated biomarkers for GBM subtyping, such as CD44. Overall, these data could assist future GBM in vitro studies and provide insights for the development of new diagnostic and therapeutic methods as well as personalized treatment strategies.
Kernohan-Woltman notch phenomenon (KWNP) is a false localising sign which may still cause diagnostic confusion. It was first described by Kernohan and Woltman in 1929, through post-mortem studies on 297 patients following cases of false localisation. They proposed that raised intracranial pressure causes uncal herniation, which can compress the contralateral cerebral peduncle against the tough tentorium, manifesting as hemiparesis ipsilateral to the primary brain lesion. A number of case reports have been written since the original description of this phenomenon, primarily secondary to intracranial bleeds, and little has been written about long-term outcome of patients who develop KNWP. We performed a literature search of all published cases of KWNP, and reviewed its clinical, pathophysiological, imaging and neurophysiological characteristics. Furthermore, we summarise the long-term outcomes of these patients as described by case reports, with the aim to improve understanding of rehabilitation potential. Thirty-eight cases were found through a PubMed search. We also included a case from our own Trust, making the total number of cases in the analysis 39. Thirty-six cases were secondary to intracranial bleeds (22 of which were traumatic), the remainder were due to an arachnoid cyst, high grade glioma, and reabsorption bone syndrome. Additional clinical manifestations to hemibrachiocrural syndrome included third nerve palsy, mydriasis of the contralateral and ipsilateral pupils, facial nerve palsies, and parkinsonism. Twenty-six (67%) patients had improvement in motor function of varying degrees, with twelve (31%) patients attaining complete motor recovery or independence. More studies on long-term outcome of patients who develop KWNP are needed to understand rehabilitation potential.
To undertake a preliminary study that uses CT texture analysis (CTTA) to quantify heterogeneity in gliomas on contrast-enhanced CT and to assess the relationship between tumour heterogeneity and grade. Retrospective analysis of contrast enhanced CT images was performed in 44 patients with histologically proven cerebral glioma between 2007 and 2010. 11 tumours were low grade (Grade I = 3; Grade II, = 8) and 33 high grade (Grade III = 10, Grade IV = 23). CTTA assessment of tumour heterogeneity was performed using a proprietary software algorithm (TexRAD) that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features). Heterogeneity was quantified as standard deviation (SD) with or without filtration. Tumour heterogeneity, size and attenuation were correlated with tumour grade. For each parameter, receiver operating characteristics characterised the diagnostic performance for discrimination of high grade from low grade glioma and of grade III tumours from grade IV. Further the CTTA was compared to the radiological diagnosis. Tumour heterogeneity correlated significantly with grade (SD without filtration rs = 0.664, p < 0.001, SD with coarse filtration (rs = 0.714, p < 0.001). Tumour size and attenuation showed only moderate correlations with tumour grade (rs = 0.426, p = 0.004 and rs = 0.447, p = 0.002 respectively). Coarse texture was the best discriminator between high and low grade tumours (AUC 0.832, p < 0.0001) and between grade III and grade IV gliomas (AUC = 0.878 p = 0.0001). Compared to the radiological diagnosis, CTTA further characterised the indetermined cases. By quantifying tumour heterogeneity, CTTA has the potential to provide a marker of tumour grade for patients with cerebral glioma. By differentiating between high and low grade tumours, CTTA could possibly assist clinical management.
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