Mild traumatic brain injury (mTBI) can induce long-term behavioral and cognitive disorders. Although the exact origin of these mTBI-related disorders is not known, they may be the consequence of diffuse axonal injury (DAI). Here, we investigated whether MRI at the subacute stage can detect lesions that are associated with poor functional outcome in mTBI by using anatomical images (T(1) ) and diffusion tensor imaging (DTI). Twenty-three patients with mTBI were investigated and compared with 23 healthy volunteers. All patients underwent an MRI investigation and clinical tests between 7 and 28 days (D15) and between 3 and 4 months (M3) after injury. Patients were divided in two groups of poor outcome (PO) and good outcome (GO), based on their complaints at M3. Groupwise differences in gray matter partial volume between PO patients, GO patients and controls were analyzed using Voxel-Based Morphometry (VBM) from T(1) data at D15. Differences in microstructural architecture were investigated using Tract-Based Spatial Statistics (TBSS) and the diffusion images obtained from DTI data at D15. Permutation-based non-parametric testing was used to assess cluster significance at p < 0.05, corrected for multiple comparisons. Twelve GO patients and 11 PO patients were identified on the basis of their complaints. In PO patients, gray matter partial volume was significantly lower in several cortical and subcortical regions compared with controls, but did not differ from that of GO patients. No difference in diffusion variables was found between GO and controls. PO patients showed significantly higher mean diffusivity values than both controls and GO patients in the corpus callosum, the right anterior thalamic radiations and the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the fronto-occipital fasciculus bilaterally. In conclusion, PO patients differed from GO patients by the presence of diffusion changes in long association white matter fiber tracts but not by gray matter partial volume. These results suggest that DTI at the subacute stage may be a predictive marker of poor outcome in mTBI.
Glioblastomas (GBMs) are highly malignant tumors characterized by microvascular proliferation and the pseudopalisading pattern of necrosis. Investigations have, therefore, focused on vascular and endothelial cell biology in GBM. Endocan, also called endothelial cell-specific molecule-1, is a proteoglycan that is secreted by endothelial cells and upregulated by proangiogenic factors. We found that endocan is not only expressed in vitro by endothelial cells but also in the T98G and U118MG human GBM cell lines. In U118MG cells, tumor necrosis factor and fibroblast growth factor 2 upregulated endocan production, whereas exposure to hypoxia or cobalt chloride, an inducer of hypoxia inducible factor 1, increased endocan release without affecting cell viability. Endocan expression in 82 brain tumors was studied by immunohistochemistry. Endocan immunoreactivity was detected in hyperplastic endothelial cells in high-grade gliomas, mostly at the tumor margins; endothelial cells were mostly endocan negative in low-grade gliomas, and it was never detected in the cerebral cortex distant from the tumors. Tumor cells in high-grade but not low-grade gliomas also expressed endocan, and it was detected in palisading cells surrounding areas of necrosis in GBM. Endothelial cell endocan immunoreactivity also correlated with shorter survival in glioma patients. Taken together, these results suggest that endocan is associated with abnormal vasculature in high-grade gliomas.
Using multivariate analysis, the following factors were found to influence survival: radiotherapy was the predominant factor followed by radical surgery, tumour location, age and chemotherapy. Patients treated with temozolomide had a markedly better survival rate than patients treated with other chemotherapies (Log-rank test P < 0.005). The values of GBM type (de novo or secondary), as well as repeated surgery and partial surgery (vs. simple biopsy) were suggested by univariate analysis but not confirmed by the COX regression method. After radical surgery, progression-free survival was correlated to overall survival (r = 0.87, P < 10e-5). CONCLUSIONS; The influence of radiotherapy on survival was greater than the influence of age, an argument supporting the proposition of radiotherapy for patients until at least age 70. In the case of recurrence, the correlation between overall survival and progression-free survival is an important factor when considering the therapeutic options. Initial radical surgery and repeated procedures dramatically influence survival. The benefit of partial surgery remains difficult to evaluate. Partial surgery could be used to decrease intracranial pressure and to minimize residual tumours in order to enable treatment by chemotherapy and radiotherapy. The value of temozolomide treatment was confirmed.
To our best knowledge, our study showed for the first time a significant association between HER2 expression and the type of GBM, with subsequent influence on survival rate. GBM with low-HER2 expression are more likely to be secondary GBM, carrying a better prognosis than de novo GBM.
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